Neurocognitive Disorders

Neurocognitive Disorders

• Advances in molecular biology, diagnostic techniques, and medication management have improved the ability to recognize and treat cognitive disorders.

• Cognition includes:

  • Memory

  • Language

  • Orientation

  • Judgment

  • Interpersonal relationships

  • Praxis (performing actions)

  • Problem-solving

• Cognitive disorders reflect disruption in one or more of these domains, often complicated by behavioral symptoms.

• Cognitive disorders exemplify the interface among neurology, medicine, and psychiatry.

  • Medical or neurologic conditions often lead to cognitive disorders.

  • These disorders are associated with behavioral symptoms.

  • Biologic insults can result in behavioral symptomatology.

• Clinicians must carefully assess the history and context before diagnosing and treating these disorders.

• Cognitive disorders can be complex, with multiplicity, comorbidity, and unclear boundaries.

• Elderly adults are most at risk for cognitive disorders.

• Dementias of late-life are particularly problematic; unrecognized dementia is a risk factor for superimposed delirium.

• Certain dementias (e.g., Lewy body dementia, late-stage Alzheimer's) may have presentations indistinguishable from delirium, except for temporal onset and lack of an acute source.

• Behavioral syndromes (anxiety, depression, sleep problems, psychosis, aggression) complicate the course of progressive dementia.

  • These symptoms can be as distressing as the primary cognitive disorder.

  • Some syndromes, like psychosis, may result from independent underlying biologies and may be additive with the primary neurodegenerative process.

• Boundaries between types of dementia and between dementia and healthy aging can be diffuse.

• Neuropathologic studies reveal mixtures of Alzheimer's, vascular, and Lewy body pathologies in dementia.

  • Pure syndromes are relatively less common.

  • Strategies for understanding/reconciling multiple pathologies are needed.

Definition of Cognitive Disorders

• Cognitive disorders are defined as follows:

Delirium

• Delirium is a condition of short-term confusion and changes in cognition.

• Four subcategories based on causes:

  • General medical condition (e.g., infection)

  • Substance-induced (e.g., cocaine, opioids, PCP)

  • Multiple causes (e.g., head trauma and kidney disease)

  • Other or multiple etiologies (e.g., sleep deprivation, medications)

Dementia (Major Neurocognitive Disorder)

• Dementia, also referred to as major neurocognitive disorder (DSM-5), is marked by severe impairment in memory, judgment, orientation, and cognition.

• Subcategories:

  • Dementia of the Alzheimer type (Alzheimer Dementia): Usually occurs in persons older than 65 years of age and is manifested by progressive intellectual disorientation and dementia, delusions, or depression

  • Vascular dementia: Caused by vessel thrombosis or hemorrhage

  • Human immunodeficiency virus (HIV) disease

  • Head trauma

  • Pick disease or frontotemporal lobar degeneration

  • Prion disease: Such as Creutzfeldt–Jakob disease (CJD), caused by a slow-growing transmittable virus

  • Substance-induced: Caused by toxin or medication (e.g., gasoline fumes, atropine)

  • Multiple etiologies

  • Not specified: If the cause is unknown

• Mild neurocognitive disorder describes a less severe form of dementia (DSM-5).

Amnestic Disorder

• Amnestic disorders are major neurocognitive disorders caused by other medical conditions.

• Marked primarily by memory impairment in addition to other cognitive symptoms.

• Causes include:

  • Medical conditions (hypoxia)

  • Toxins or medications (e.g., marijuana, diazepam)

  • Unknown causes

Clinical Evaluation

• During history taking, clinicians seek to elicit the development of the illness.

• Subtle cognitive disorders, fluctuating symptoms, and progressing disease processes may be tracked effectively.

• The clinician should obtain a detailed rendition of changes in the patient’s daily routine involving such factors as self-care, job responsibilities, and work habits; meal preparation; shopping and personal support; interactions with friends; hobbies and sports; reading interests; religious, social, and recreational activities; and ability to maintain personal finances.

• Understanding the past life of each patient provides an invaluable source of baseline data regarding changes in function, such as attention and concentration, intellectual abilities, personality, motor skills, and mood and perception.

• The examiner explores what the patient considers essential to their lifestyle and how the clinical condition affects these.

• This helps to assess both the disease and the success of future therapies.

Neuropsychiatric Mental Status Examination

The neuropsychiatric mental status examination includes evaluation of:

• A. General Description

  1. General appearance, dress, sensory aids (glasses, hearing aid)

  2. Level of consciousness and arousal

  3. Attention to environment

  4. Posture (standing and seated)

  5. Gait

  6. Movements of limbs, trunk, and face (spontaneous, resting, and after instruction)

  7. General demeanor (including evidence of responses to internal stimuli)

  8. Response to examiner (eye contact, cooperation, ability to focus on interview process)

  9. Native or primary language

• B. Language and Speech

  1. Comprehension (words, sentences, simple and complex commands, and concepts)

  2. Output (spontaneity, rate, fluency, melody or prosody, volume, coherence, vocabulary, paraphasic errors, complexity of usage)

  3. Repetition

  4. Other aspects

     • Object naming

     • Color naming

     • Body part identification

     • Ideomotor praxis to command

• C. Thought

  1. Form (coherence and connectedness)

  2. Content

     • Ideational (preoccupations, overvalued ideas, delusions)

     • Perceptual (hallucinations)

• D. Mood and Affect

  1. Internal mood state (spontaneous and elicited; sense of humor)

  2. Future outlook

  3. Suicidal ideas and plans

  4. Demonstrated emotional status (congruence with mood)

• E. Insight and Judgment

  1. Insight

     • Self-appraisal and self-esteem

     • Understanding of current circumstances

     • Ability to describe personal, psychological, and physical status

  2. Judgment

     • Appraisal of major social relationships

     • Understanding of personal roles and responsibilities

• F. Cognition

  1. Memory

     • Spontaneous (as evidenced during interview)

     • Tested (incidental, immediate repetition, delayed recall, cued recall, recognition; verbal, nonverbal; explicit, implicit)

  2. Visuospatial skills

  3. Constructional ability

  4. Mathematics

  5. Reading

  6. Writing

  7. Fine sensory function (stereognosis, graphesthesia, two-point discrimination)

  8. Finger gnosis

  9. Right–left orientation

  10. Executive functions

  11. Abstraction

Mental Status Examination

• After taking a thorough history, the clinician’s primary tool is the assessment of the patient’s mental status.

• As with the physical examination, the mental status examination is a means of surveying functions and abilities to allow a definition of personal strengths and weaknesses.

• It is a repeatable, structured assessment of symptoms and signs that promotes effective communication among clinicians.

• It also establishes the basis for future comparison, essential for documenting therapeutic effectiveness, and it allows comparisons between different patients, with a generalization of findings from one patient to another.

• When testing cognitive functions, the clinician should evaluate memory; visuospatial and constructional abilities; and reading, writing, and mathematical abilities.

• The assessment of abstraction ability is also practical. However, many things can affect proverb interpretation, such as culture and education, and any interpretation should happen in that context.

Pathology and Laboratory Examination

• Psychiatric evaluations should be interpreted in the context of thorough clinical and laboratory assessments.

• Psychiatric and neuropsychiatric patients require a careful physical examination, particularly when issues exist that involve etiologically related or comorbid medical conditions.

• When consulting internists and other medical specialists, the clinician must ask specific questions to focus on the differential diagnostic process and use the consultation most effectively.

• Most systemic medical or primary cerebral diseases that lead to psychopathological disturbances also manifest with a variety of peripheral or central abnormalities.

• A screening laboratory evaluation is sought initially and may be followed by a variety of ancillary tests to increase the diagnostic specificity.

Electroencephalography

• Electroencephalography (EEG) is an easily accessible, noninvasive test of brain dysfunction that has a high sensitivity for many disorders but relatively low specificity.

• Beyond its recognized uses in epilepsy, EEG’s highest utility is in detecting altered electrical rhythms associated with mild delirium, space-occupying lesions, and continuing complex partial seizures (in which the patient remains conscious, although behaviorally impaired).

• EEG is also sensitive to metabolic and toxic states, often showing a diffuse slowing of brain activity.

Computed Tomography and Magnetic Resonance Imaging

• Computed tomography (CT) and magnetic resonance imaging (MRI) have proved to be powerful neuropsychiatric research tools.

• Recent developments in MRI allow the direct measurement of structures such as the thalamus, basal ganglia, hippocampus, and amygdala, as well as temporal and apical areas of the brain and the structures of the posterior fossa.

• MRI has mostly replaced CT as the most utilitarian and cost-effective method of imaging in neuropsychiatry.

• CT is still the test of choice for patients with acute cerebral hemorrhages or hematomas, but these patients infrequently present in psychiatric settings.

• MRI better discriminates the interface between gray and white matter and is useful in detecting a variety of white matter lesions in the periventricular and subcortical regions.

• The pathophysiologic significance of such findings remains to be defined.

• White matter abnormalities occur in younger patients with multiple sclerosis or HIV infection and older patients with hypertension, vascular dementia, or dementia of the Alzheimer type.

• The prevalence of these abnormalities increases in healthy, aging individuals who have no defined disease process.

• In general, the highest utility of neuroimaging in the evaluation of patients with dementia arises from what it may exclude (tumors, vascular disease) rather than what it can demonstrate specifically.

Screening Laboratory Tests

General Tests

• Complete blood cell count

• Erythrocyte sedimentation rate

• Electrolytes

• Glucose

• Blood urea nitrogen and serum creatinine

• Liver function tests

• Serum calcium and phosphorus

• Thyroid function tests

• Serum protein

• Levels of all drugs

• Urinalysis

• Pregnancy test for women of childbearing age

• Electrocardiography

Ancillary Laboratory Tests

• Blood

  • Blood cultures

  • Rapid plasma reagin test

  • Human immunodeficiency virus (HIV) testing (enzyme-linked immunosorbent assay [ELISA] and Western blot)

  • Serum heavy metals

  • Serum copper

  • Ceruloplasmin

  • Serum B12, red blood cell (RBC) folate levels

• Urine

  • Culture

  • Toxicology

  • Heavy metal screen

• Electrography

  • Electroencephalography

  • Evoked potentials

  • Polysomnography

  • Nocturnal penile tumescence

• Cerebrospinal fluid

  • Glucose, protein

  • Cell count

  • Cultures (bacterial, viral, fungal)

  • Cryptococcal antigen

  • Venereal Disease Research Laboratory (VDRL) test

• Radiography

  • Computed tomography

  • Magnetic resonance imaging

  • Positron emission tomography

  • Single photon emission computed tomography

Brain Biopsy

• A brain needle biopsy can diagnose a variety of disorders: Alzheimer disease, autoimmune encephalopathy, and tumors.

• It is conducted stereotactically and indicated when no other investigative techniques such as MRI or lumbar puncture have been sufficient to make a diagnosis.

• The procedure is not without risk in that seizures may occur if scar tissue forms at the biopsy site.

Neuropsychologic Testing

• Neuropsychologic testing provides a standardized, quantitative, reproducible evaluation of a patient’s cognitive abilities.

• Such procedures may be useful for initial evaluation and periodic assessment.

• Tests are available that assess abilities across the broad array of cognitive domains, and many offer comparative normative groups or adjusted scores based on normative samples.

• The clinician seeking neuropsychologic consultation should understand enough about the strengths and weaknesses of selected procedures to benefit fully from the results obtained.

3.1 Delirium

• Delirium is an acute decline in both the level of consciousness and cognition with particular impairment in attention.

• A life-threatening yet potentially reversible disorder of the central nervous system (CNS), delirium often involves perceptual disturbances, abnormal psychomotor activity, and sleep cycle impairment.

• Health care workers often underrecognize delirium.

• Part of the problem is that the syndrome has a variety of other names.

• The hallmark symptom of delirium is an impairment of consciousness, usually occurring in association with global impairments of cognitive functions.

• Abnormalities of mood, perception, and behavior are common psychiatric symptoms.

• Tremor, asterixis, nystagmus, incoordination, and urinary incontinence are common neurologic symptoms.

• Classically, delirium has a sudden onset (hours or days), a brief and fluctuating course, and rapid improvement when we can identify the cause and eliminate it, but each of these characteristic features can vary in individual patients.

• Physicians must recognize delirium to identify and treat the underlying cause and to avert the development of delirium-related complications such as accidental injury because of the patient’s clouded consciousness.

Delirium by Other Names

• Intensive care unit psychosis

• Acute confusional state

• Acute brain failure

• Encephalitis

• Encephalopathy

• Toxic metabolic state

• Central nervous system toxicity

• Paraneoplastic limbic encephalitis

• Sundowning

• Cerebral insufficiency

• Organic brain syndrome

Delirium DSM-5 ICD-10

Diagnosis and Clinical Features

• Delirium's diagnostic approaches involve one or more systemic or cerebral derangements that affect brain function.

Mrs. K Case

• A 70-year-old woman, Mrs. K, was brought to the emergency department by the police after complaints from neighbors.

• She was found in a state of neglect, confusion, and unresponsiveness.

• She knew her name and address but not the date.

• She reported feeling sick and weak, with pains in her shoulder, and had not eaten for three days.

• She acknowledged seeing a psychiatrist in the past for trouble sleeping.

Core Features of Delirium

• Altered consciousness (usually decreased level)

• Altered attention (diminished ability to focus, sustain, or shift attention)

• Other cognitive dysfunctions:

  • Disorientation (especially to time and space)

  • Impaired memory

• Typical course:

  • Relatively rapid onset (usually hours to days)

  • Brief duration (usually days to weeks)

  • Marked, unpredictable fluctuations in severity

  • Sometimes worse at night (sundowning), ranging from periods of lucidity to severe cognitive impairment and disorganization

• Associated clinical features are often present and may be prominent.

• EEG usually shows diffuse slowing of background activity, although patients with delirium caused by alcohol or sedative-hypnotic withdrawal have low-voltage fast activity.

• The primary neurotransmitter hypothesized to be involved in delirium is acetylcholine, and the major neuroanatomical area is the reticular formation.

• The reticular formation of the brainstem is the principal area regulating attention and arousal; the major pathway implicated in delirium is the dorsal tegmental pathway, which projects from the mesencephalic reticular formation to the tectum and thalamus.

• Studies have reported that a variety of delirium-inducing factors result in decreased acetylcholine activity in the brain.

• One of the most common causes of delirium is toxicity from too many prescribed medications with anticholinergic activity.

• The delirium associated with alcohol withdrawal correlates with hyperactivity of the locus ceruleus and its noradrenergic neurons.

• Serotonin and glutamate are also likely involved.

Physical and Laboratory Examinations

• Delirium is usually diagnosed at the bedside and presents as a sudden onset of symptoms.

• A bedside mental status examination—such as the Mini-Mental State Examination—can be used to document the cognitive impairment and to provide a baseline from which to measure the patient’s clinical course.

• The physical examination often reveals clues to the cause of the delirium.

• The presence of a known physical illness or a history of head trauma or alcohol or other substance use disorder increases the likelihood of the diagnosis.

• The laboratory workup of a patient with delirium should include standard tests and additional studies indicated by the clinical situation.

• In delirium, the EEG characteristically shows a generalized slowing of activity and may be useful in differentiating delirium from depression or psychosis.

• The EEG of a delirious patient sometimes shows focal areas of hyperactivity.

• In rare cases, it may be challenging to differentiate delirium related to epilepsy from delirium related to other causes.

Differential Diagnosis

Delirium versus Dementia

• Several clinical features help distinguish delirium from dementia.

• The major differential points between dementia and delirium are the time to development of the condition and the fluctuation in the level of attention in delirium compared with relatively consistent attention in dementia.

• The time to development of symptoms is usually short in delirium, and except for vascular dementia caused by stroke, it is usually gradual and insidious in dementia.

• Although both conditions include cognitive impairment, the changes in dementia are more stable over time and, for example, usually do not fluctuate over a day.

• A patient with dementia is usually alert; a patient with delirium has episodes of decreased consciousness.

• Occasionally, delirium occurs in a patient with dementia, a condition known as beclouded dementia.

• A dual diagnosis of delirium exists when there is a definite history of preexisting dementia.

Delirium versus Schizophrenia or Depression

• Delirium should be differentiated from schizophrenia and depressive disorder.

• Some patients with psychotic disorders, usually schizophrenia or manic episodes, can have periods of extremely disorganized behavior challenging to distinguish from delirium.

• In general, however, the hallucinations and delusions of patients with schizophrenia are more constant and better organized than those of patients with delirium.

• Patients with schizophrenia usually experience no change in their level of consciousness or their orientation.

• Patients with hypoactive symptoms of delirium may appear somewhat similar to severely depressed patients, but their confusion can help differentiate, as can an EEG.

• Other psychiatric diagnoses to consider in the differential diagnosis of delirium are brief psychotic disorder, schizophreniform disorder, and dissociative disorders.

• Patients with factitious disorders may attempt to simulate the symptoms of delirium but usually reveal the factitious nature of their symptoms by inconsistencies on their mental status examinations, and an EEG can easily separate the two diagnoses.

Course and Prognosis

• Although the onset of delirium is usually sudden, prodromal symptoms (e.g., restlessness and fearfulness) can occur in the days preceding the onset of florid symptoms.

• The symptoms of delirium usually persist as long as the causally relevant factors are present, although delirium generally lasts less than 1 week.

• After identification and removal of the causative factors, the symptoms of delirium usually recede over a 3- to 7-day period, although some symptoms may take up to 2 weeks to resolve completely.

• The older the patient and the longer the patient has been delirious, the longer the delirium takes to resolve.

• Recall of what transpired during a delirium, once it is over, is characteristically spotty; a patient may refer to the episode as a bad dream or a nightmare only vaguely remembered.

• The occurrence of delirium is associated with a high mortality rate in the ensuing year, primarily because of the severe nature of the associated medical conditions that lead to delirium.

• Whether delirium progresses to dementia has not been demonstrated in carefully controlled studies, although many clinicians believe that they have seen such a progression.

• A clinical observation that has been validated by some studies, however, is that depression or posttraumatic stress may follow a delirium.

Treatment

• In treating delirium, the primary goal is to treat the underlying cause.

• When the underlying condition is anticholinergic toxicity, physostigmine salicylate, 1 to 2 mg intravenously or intramuscularly, may help.

  • We may have to repeat the dose every 15 to 30 minutes.

• The other important goal of treatment is to provide physical, sensory, and environmental support.

• Physical support is necessary so that delirious patients do not get into situations in which they may have accidents.

• Patients with delirium should be neither sensory deprived nor overly stimulated by the environment.

• A familiar person staying in the room, such as a friend or relative, may help.

• Familiar pictures and decorations; the presence of a clock or a calendar; and regular orientations to person, place, and time help make patients with delirium comfortable.

• Delirium can sometimes occur in older patients wearing eye patches after cataract surgery (“black-patch delirium”).

• Such patients can be helped by placing pinholes in the patches to let in some stimuli or by occasionally removing one patch at a time during recovery.

Pharmacotherapy

• The three significant delirium symptoms that may require pharmacologic treatment are psychosis, agitation, and insomnia.

Psychosis

• A commonly used drug for psychosis is haloperidol.

• Depending on a patient’s age, weight, and physical condition, the initial dose may range from 2 to 5 mg intramuscularly, repeated in an hour if the patient remains agitated.

• As soon as the patient is calm, oral medication in liquid concentrate or tablet form should begin.

• Two daily oral doses should suffice, mostly at bedtime.

• The oral equivalent is about 1.5 times the parenteral dose.

• The effective total daily dose of haloperidol may range from 5 to 40 mg for most patients with delirium.

• Haloperidol may cause a prolonged QT interval.

  • Clinicians should evaluate baseline and periodic electrocardiograms as well as monitor the cardiac status of the patient.

• Droperidol is a butyrophenone available as an alternative intravenous (IV) formulation, although careful monitoring of the electrocardiogram may be prudent with this treatment.

  • The U.S. Food and Drug Administration (FDA) issued a Black Box Warning because of cases of patients with QT prolongation and torsades de pointes receiving droperidol.

  • Because of its potential for serious proarrhythmic effects and death, it should be used only in patients who do not respond well to other treatments.

• Phenothiazines should be avoided in delirious patients because these drugs are associated with significant anticholinergic activity.

Agitation

• Agitation is a poorly defined symptom that can range from distressed anxiety to physical aggression.

• Because of the ambiguity of the term, agitation is challenging to study.

• However, some scales are available to aid research, such as the Richmond Agitation-Sedation Scale.

• Many medications have anecdotal support. However, studies on the pharmacologic treatment of agitation in delirium are disappointing.

• The antipsychotics are most commonly used.

  • The approach is analogous to the above approach for psychosis in delirium, with adjustments for the severity and prolongation of the delirium.

• Sodium valproate given IV may be useful when antipsychotics fail.

• For severe agitation, dexmedetomidine, an α2-adrenoreceptor agonist that is used as a sedative, can help sedate a patient, mainly a mechanically ventilated patient, without the deliriogenic effects of many other sedatives.

• Second-generation antipsychotics, such as risperidone, clozapine, olanzapine, quetiapine, ziprasidone, and aripiprazole, may be considered for delirium management, but clinical trial experience with these agents for delirium is limited.

• Ziprasidone appears to have an activating effect and may not be appropriate in delirium management.

• Olanzapine is available for intramuscular (IM) use and as a rapidly disintegrating oral preparation.

  • These routes of administration may be preferable for some patients with delirium who are poorly compliant with medications or who are too sedated to swallow medications safely.

Insomnia

• Insomnia is difficult to treat.

• Benzodiazepines might be helpful; however, they risk worsening a patient’s confusion.

• Also, there is no conclusive evidence to support the use of benzodiazepines in non–alcohol-related delirium.

• If pain is the cause, a physician should not hesitate to prescribe opioids for both their analgesic and sedative effects.

• Melatonin is occasionally used but with mixed support and low-quality studies.

Treatment in Special Populations

Parkinson Disease

• In Parkinson disease, antiparkinsonian agents can cause delirium.

• If coexistent dementia is present, delirium is twice as likely to develop in patients with Parkinson disease with dementia receiving antiparkinsonian agents than in those without dementia.

• Decreasing the dosage of the antiparkinsonian agent has to be weighed against a worsening of motor symptoms.

• If we cannot reduce the antiparkinsonian agents, or if the delirium persists after we do, an antipsychotic may help.

  • However, this risks worsening the disorder.

• The FDA has approved pimavanserin for psychosis in Parkinson’s.

  • It appears to be an inverse agonist and antagonist activity of serotonin 5-HT2A and possibly 5-HT2C, with no appreciable affinity for dopamine.

• Clozapine may also help and has empirical support.

• Quetiapine has not been as rigorously studied as clozapine and may have parkinsonian side effects, but it is used in clinical practice to treat psychosis in Parkinson disease.

Terminally Ill Patients

• When delirium occurs in the context of a terminal illness, issues about advanced directives and the existence of a health care proxy become more significant.

• This scenario emphasizes the importance of early development of advance directives for health care decision making while a person can communicate the wishes regarding the extent of aggressive diagnostic tests at life’s end.

• The focus may change from an aggressive search for the etiology of the delirium to one of palliation, comfort, and assistance with dying.

Physical Examination of the Delirious Patient

Laboratory Workup of the Patient with Delirium

Standard studies

• Blood chemistries (including electrolytes, renal and hepatic indexes, and glucose)

• Complete blood count with white cell differential

• Thyroid function tests

• Serologic tests for syphilis

• Human immunodeficiency virus (HIV) antibody test

• Urinalysis

• Electrocardiogram

• Electroencephalogram

• Chest radiograph

• Blood and urine drug screens

Additional tests when indicated

• Blood, urine, and cerebrospinal fluid cultures

• B12, folic acid concentrations

• Computed tomography or magnetic resonance imaging brain scan

• Lumbar puncture and CSF examination

Frequency of Clinical Features of Delirium Contrasted with Dementia

Pharmacologic Treatment of Delirium

Dementia (Major Neurocognitive Disorder)

• Dementia is a disease process characterized by progressive cognitive impairment while maintaining clear consciousness.

• It is distinct from low intellectual functioning or mental retardation, which are developmental and static conditions.

• Dementia represents a decline from a previous level of cognitive functioning.

• Dementia impacts multiple cognitive domains, causing significant impairment in social and occupational functioning.

• Types of dementias based on etiology include:

  • Alzheimer's disease

  • Dementia with Lewy bodies

  • Vascular dementia

  • Frontotemporal dementia

  • Traumatic brain injury (TBI)

  • HIV

  • Prion disease

  • Parkinson's disease

  • Huntington's disease

• Other medical, neurological conditions, and various substances can also cause dementia.

• Critical clinical points:

  • Identification of the syndrome

  • Clinical workup to determine the cause

• The disorder can be progressive or static, permanent or reversible.

• An underlying cause is always assumed, although it may not always be identifiable.

• Potential reversibility depends on the underlying condition and the availability and effectiveness of treatment.

• Approximately 15% of dementia cases are reversible with timely and effective treatment prior to irreversible damage.

Diagnosis and Clinical Features of Dementia

• DSM-5 differentiates between major and minor cognitive disorders based on levels of functioning, but the etiology is similar.

• DSM-5 and ICD-10 approaches to diagnosing dementia:

  • Symptoms: Significant (Major) or moderate (Minor) decline in cognitive functioning in areas such as attention, executive function, learning/memory, language, perceptual-motor skills, and social cognition.

  • Diagnoses should specify whether the disorder is major or minor (e.g., minor neurocognitive disorder with Lewy bodies).

  • The specific cause of dementia defines the diagnosis.

  • Requires ≥1 symptom based on the aforementioned criteria.

  • Exclusions: The symptoms should not be the result of delirium or another mental disorder.

  • Psychosocial Impact: Some impairments in the ability to independently perform activities of daily living.

  • Symptom Specifiers: Refer to the specifiers for the specific disorders and note the presence of behavioral disturbances.

  • Severity Specifiers: Based on what is impaired and the level of impairment:

    • Mild: Instrumental activities of daily life (e.g., cooking, paying bills) are impaired.

    • Moderate: Basic activities of daily life (e.g., eating, dressing) are impaired.

    • Severe: Impaired in all activities, fully dependent on others.

• DSM-5 specifies various types of dementia based on their cause; diagnostic approaches to major etiologies are compared in Tables 3-15 to 3-24.

• Diagnosis is made through clinical examination (including mental status examination) and information from family, friends, and employers.

• Complaints of personality change in patients older than 40 years should raise suspicion for dementia.

• Clinicians should note complaints of intellectual impairment and forgetfulness, as well as attempts to conceal cognitive deficits.

• Characteristic behaviors can include excessive orderliness, social withdrawal, relating events in minute detail, and sudden outbursts of anger or sarcasm.

• Observable signs include lability of emotions, sloppy grooming, uninhibited remarks, silly jokes, or a dull, apathetic facial expression, especially with memory impairment.

• Memory impairment is typically an early and prominent feature, especially in cortical dementias like Alzheimer's.

Memory Impairment in Dementia

• Early in dementia, memory impairment is mild, particularly for recent events (e.g., forgetting telephone numbers, conversations, and daily events).

• As dementia progresses, memory impairment becomes severe, with retention limited to the earliest learned information (e.g., place of birth).

• Memory is crucial for orientation to person, place, and time, which becomes progressively affected.

• Patients may forget how to return to their rooms after using the bathroom.

• Despite severe disorientation, the level of consciousness remains unimpaired.

Neurocognitive Disorders

• Neurocognitive Disorder due to Alzheimer's Disease (DSM-5 & ICD-10):

  • Symptoms: Decline in memory and learning.

  • Progressive decline with no significant periods of stability.

  • No evidence of mixed causes.

  • (Probable): Evidence of a genetic cause (family history/genetic testing) OR all three symptoms listed above.

  • (Possible): Some, but not all, of the probable criteria are met.

• Frontotemporal Neurocognitive Disorder (DSM-5 & ICD-10):

  • Progressive decline in behavior, social cognition, executive function, and/or language, with relative sparing of learning, memory, and perceptual-motor function.

  • Behavioral Variant: Notable symptoms are disinhibition, apathy, ↓ sympathy/empathy, perseveration/stereotypies, and hyperorality/dietary changes.

  • Language Variant: Notable symptoms are affected language (word finding, naming, grammar, less spontaneous speech).

  • (Probable): Evidence of a genetic cause (family history/genetic testing) and neuroimaging evidence of frontal/temporal pathology.

  • (Possible): Some, but not all, probable criteria are met.

• Neurocognitive Disorder With Lewy Bodies (DSM-5 & ICD-10):

  • Core Features:

    • Fluctuating cognition, attention, and alertness.

    • Recurrent well-formed visual hallucinations.

    • Parkinsonian symptoms beginning after cognitive decline.

  • Suggestive Features:

    • REM sleep behavior disorder.

    • Severe neuroleptic sensitivity.

  • (Probable): ≥2 core features, or 1 core feature + 1 suggestive feature.

  • (Possible): 1 core feature.

• Vascular Neurocognitive Disorder (DSM-5 & ICD-10):

  • History + imaging/physical findings of cerebrovascular disease.

  • Cognitive decline typical of vascular pathology (≥1):

    • Cognitive decline after CV event.

    • Cognitive areas mainly complex attention/frontal-executive function.

  • (Probable):

    • Neuroimaging evidence of CV disease in the brain.

    • Neurocognitive symptoms are associated with CV events.

  • Clinical/genetic evidence of CV disease.

  • (Possible):

    • No neuroimaging.

    • No documented temporal relationship between CV events and cognitive changes.

• Neurocognitive Disorder due to Traumatic Brain Injury (DSM-5 & ICD-10):

  • History of traumatic brain injury, with associated noncognitive symptoms.

  • Neurocognitive symptoms (≥1):

    • Loss of consciousness.

    • Amnesia following trauma.

    • Confusion/disorientation.

    • Neuroimaging evidence of injury/Neurologic symptoms.

• Neurocognitive Disorder due to HIV Infection (DSM-5 & ICD-10):

  • HIV diagnosis with associated cognitive symptoms.

• Neurocognitive Disorder due to Prion Disease (DSM-5 & ICD-10):

  • Cognitive impairment with subtle onset and rapid progression.

• Neurocognitive Disorder due to Parkinson's Disease (DSM-5 & ICD-10):

  • Occurring in the context of Parkinson's disease, with subtle onset and gradual progression.

  • (Probable): No evidence of mixed etiology, and Parkinson's disease precedes cognitive symptoms.

  • (Possible): One of the following: No evidence of mixed etiology OR Parkinson's disease precedes cognitive symptoms.

• Neurocognitive Disorder due to Huntington's Disease (DSM-5 & ICD-10):

  • Occurring in the context of Huntington's disease, with subtle onset and gradual progression.

  • Caused by an autosomal dominant gene with slow progression and motor symptoms (chorea).

Language, Psychiatric, and Neurologic Changes in Dementia

• Dementias affecting the cortex can affect language abilities.

• Changes in personality are disturbing for families; preexisting traits may be accentuated during dementia.

• Patients may become introverted and less concerned about the impact of their behavior on others.

• Paranoid delusions can cause hostility toward family and caretakers.

• Frontal and temporal involvement may lead to marked personality changes, irritability, and explosiveness.

• Hallucinations occur in 20-30% of patients, primarily those with Alzheimer's.

• Delusions occur in 30-40% of patients, typically paranoid or persecutory and unsystematized.

• Physical aggression and violence are common with psychotic symptoms.

• Depression and anxiety are significant symptoms in 40-50% of patients, though full depressive disorder is present in only 10-20%.

• Patients may exhibit pathologic laughter or crying without apparent provocation.

• Apraxias and agnosias are common.

• Other neurologic signs may include seizures (10% in Alzheimer's, 20% in vascular dementia) and atypical presentations.

• Primitive reflexes may be present, and myoclonic jerks occur in 5-10% of patients.

• Patients exhibit a reduced ability to apply the "abstract attitude," struggling with generalization, concept formation, and understanding similarities/differences.

• Problem-solving, logical reasoning, and sound judgment are compromised.

• Catastrophic reactions, marked by agitation due to awareness of intellectual deficits under stress, may occur.

• Patients may compensate to avoid demonstrating failures in intellectual performance.

• Lack of judgment and poor impulse control are common, especially in frontal lobe dementias.

• Manifestations include coarse language, inappropriate jokes, neglect of personal appearance/hygiene, and disregard for social rules.

Additional Diagnosis Types of Dementia in DSM-5

• Neurocognitive disorder due to another medical condition

• Neurocognitive disorder due to multiple etiologies

• Substance/medication-induced neurocognitive disorder

• Unspecified neurocognitive disorder

• Vascular dementia may involve headaches, dizziness, faintness, weakness, focal neurologic signs, and sleep disturbances related to cerebrovascular disease.

• Pseudobulbar palsy, dysarthria, and dysphagia are more common in vascular dementia.

• Sundowner Syndrome: Characterized by drowsiness, confusion, ataxia, and accidental falls in older, sedated individuals or dementia patients reacting to psychoactive drugs, and when external stimuli are diminished.

Vascular and Substance-Induced Dementia

• Vascular Dementia: General symptoms are similar to Alzheimer's, but diagnosis requires clinical or laboratory evidence of a vascular cause. Deterioration is more stepwise compared to Alzheimer's.

• Substance-Induced Persisting Dementia: Listed with both dementias and substance-related disorders, implicating alcohol, inhalants, sedatives, hypnotics, anxiolytics, and other/unknown substances.

• Alcohol-Induced Persisting Dementia: Requires meeting dementia criteria, differentiating from amnesia caused by thiamine deficiency (Korsakoff psychosis). Other cognitive functions (attention, concentration) can be impaired in Wernicke-Korsakoff syndrome. Mood changes related to alcohol abuse must be ruled out.

• Prevalence of alcohol-related dementia is approximately 4% of dementias.

Pathology, Physical Findings, and Laboratory Examination

• A comprehensive laboratory workup is essential to detect reversible causes of dementia and to provide a definitive diagnosis.

• The evaluation should be guided by clinical suspicion based on history, physical, and mental status examination results.

• MRI is useful in differentiating Alzheimer's from vascular dementia.

• Single-photon emission computed tomography (SPECT) can detect patterns of brain metabolism in different dementias.

• A general physical examination may reveal systemic diseases causing brain dysfunction or systemic diseases related to CNS processes.

• The detection of Kaposi sarcoma should raise suspicion for AIDS and AIDS dementia complex.

• Focal neurologic findings are more common in vascular than degenerative disease.

• Frontal lobe signs and primitive reflexes often indicate more significant progression.

Differential Diagnosis

• Dementia of the Alzheimer Type vs. Vascular Dementia:

  • Vascular dementia classically presents with decremental deterioration related to cerebrovascular disease, although this is not always apparent.

  • Focal neurologic symptoms and risk factors for cerebrovascular disease are more common in vascular dementia.

• Vascular Dementia vs. Transient Ischemic Attacks (TIAs):

  • TIAs are brief episodes of focal neurologic dysfunction lasting less than 24 hours, often due to microembolization.

  • TIAs usually resolve without significant pathologic alteration.

  • Untreated TIAs can lead to brain infarction.

  • Symptoms of vertebrobasilar disease reflect disturbances in the brainstem or occipital lobe, while carotid distribution symptoms reflect unilateral retinal or hemispheric abnormality.

  • Anticoagulant therapy, antiplatelet agglutinating drugs, and vascular surgery can reduce infarction risk in TIA patients.

• Delirium:

  • Delirium has rapid onset, brief duration, fluctuating cognitive impairment, nocturnal exacerbation, disturbed sleep-wake cycle, and prominent disturbances in attention and perception.

• Depression:

  • Depression can present with cognitive impairment, sometimes referred to as pseudodementia or depression-related cognitive dysfunction.

  • Patients with depression-related cognitive dysfunction have prominent depressive symptoms, more insight into their symptoms, and often a history of depressive episodes.

  • Memory impairment from depression usually responds to antidepressant medication.

Differentiating Depression-Related Cognitive Dysfunction from Dementia

• Depression: Family always aware of dysfunction and its severity, onset dated with precision, rapid symptom progression, history of psychiatric dysfunction common, detailed complaints of cognitive loss, emphasizes disability, highlights failures, struggles to perform tasks, strong sense of distress, behavior incongruent with severity, attention and concentration well preserved, "don't know" answers typical, memory loss severe for recent and remote events, variability in performance.

• Dementia: Family often unaware of dysfunction, onset dated broadly, slow symptom progression, history of psychiatric dysfunction unusual, vague complaints of cognitive loss, conceals disability, delights in accomplishments, makes little effort to perform tasks, often unconcerned, behavior compatible with severity, attention and concentration faulty, near-miss answers frequent, memory loss more severe for recent events, consistently poor performance.

• Malingering and Factitious Disorder: Simulated memory loss is erratic and inconsistent. True dementia involves loss of time/place memory before person memory and recent memory before remote memory.

• Schizophrenia: Associated with acquired intellectual impairment, but symptoms are less severe than psychosis and thought disorder.

• Normal Aging: Minor memory problems can occur without significant cognitive decline, termed benign senescent forgetfulness or age-associated memory impairment; these do not significantly interfere with social or occupational behavior.

• Other Disorders: Intellectual disability begins in childhood and does not include memory impairment. Amnestic disorder involves circumscribed loss of memory without deterioration. Pituitary disorders should be ruled out.

Course and Prognosis

• The classic course of dementia involves onset in the 60s with gradual deterioration over 5-10 years, leading to death.

• Age of onset and rate of deterioration vary among different types of dementia.

• Average survival expectation for Alzheimer's is approximately 8 years (range: 1-20 years).

• Early onset or family history of dementia may indicate a more rapid course.

• Complete medical and neurologic workup is necessary after diagnosing dementia because 10-15% of patients have potentially reversible conditions if treatment is initiated early.

• Gradual onset of symptoms is associated with Alzheimer's, vascular dementia, endocrinopathies, brain tumors, and metabolic disorders.

• Sudden onset can occur with head trauma, cardiac arrest with cerebral hypoxia, or encephalitis.

• Early symptoms of dementia may be subtle but become conspicuous as the disease progresses.

• Benzodiazepines or alcohol can precipitate agitated, aggressive, or psychotic behavior.

• In terminal stages, patients become profoundly disoriented, incoherent, amnestic, and incontinent.

• Symptoms may progress slowly or recede somewhat with psychosocial and pharmacologic treatment.

• Symptom regression is possible in reversible dementias after initiating treatment.

• The course varies from steady progression (Alzheimer's) to incrementally worsening (vascular dementia) to stable (head trauma).

Psychosocial Determinants and Treatment

• Psychosocial Determinants:

  • Severity and course of dementia are affected by psychosocial factors.

  • Higher premorbid intelligence and education improve compensation for intellectual deficits.

  • Rapid onset of dementia leads to fewer defenses.

  • Anxiety and depression can intensify symptoms.

• Treatment:

  • Verification of the diagnosis is the first step.

  • Progression may be halted or reversed with appropriate therapy.

  • Preventive measures are essential, particularly in vascular dementia (diet, exercise, control of diabetes and hypertension).

  • Pharmacologic agents include antihypertensive, anticoagulant, or antiplatelet agents.

  • Blood pressure control should aim for the higher end of normal to improve cognitive function in vascular dementia.

Psychosocial Theories and Pharmacotherapy

• Psychosocial Therapies:

  • Deterioration of mental faculties has significant psychological meaning for patients.

  • Patients lose recent memory before remote memory, leading to distress.

  • Self is a product of brain functioning; identity fades as the illness progresses.

  • Emotional reactions stem from the realization that the sense of self is disappearing.

  • Supportive and educational psychotherapy helps patients understand the nature and course of their illness.

  • Assistance in grieving, accepting disability, and addressing self-esteem issues is beneficial.

  • Maximizing intact functioning by helping patients identify activities for successful functioning.

  • Clinicians can help patients deal with defective functions.

  • Psychodynamic interventions with family members are helpful to address guilt, grief, anger, and exhaustion.

  • Clinicians must be aware of caregivers' tendencies to blame themselves or others.

• Pharmacotherapy:

  • Sedative-hypnotics for insomnia and anxiety, antidepressants for depression, and antipsychotic drugs for delusions and hallucinations may be prescribed.

  • Avoid drugs with high anticholinergic activity.

  • Donepezil, rivastigmine, galantamine, and tacrine are cholinesterase inhibitors used for mild to moderate cognitive impairment in Alzheimer's disease.

  • Memantine protects neurons from excessive amounts of glutamate.

Other Treatment Approaches and Epidemiology

• A very active area of drug research that includes cognitive-enhancing activity. Novel strategies focus on β-amyloid plaques and neurofibrillary tangles.

• In the case of amyloid plaques, attempts to reduce their formation, aggregation, and increase their clearance are underway.

• Several monoclonal and polyclonal antibody vaccines are being tested.
  *Estrogen replacement therapy may reduce the risk of cognitive decline in postmenopausal women; however, data is correlational and clinical trials have been largely disappointing.

• Novel strategies are focusing on Beta-amyloid plaques and neurofibrillary tangles associated with Alzheimer's and some other neurodegenerative disorders. In the case of amyloid plaques, attempts to reduce their formation, aggregation, and increase their clearance are underway, and several monoclonal and polyclonal antibody vaccines are being tested.

• Exercise improves cognition in healthy adults, and there is some evidence of benefit in dementia, particularly in the early stages.

• Epidemiology:

  • The prevalence of dementia is rising with the aging population.

  • Prevalence rates:

    • 5% in the general population older than 65 years.

    • 20-40% in the general population older than 85 years.

    • 15-20% in outpatient general medical practices.

    • 50% in chronic care facilities.

  • Alzheimer's accounts for 50-60% of all dementia cases.

Prevalence and Etiology of Dementia

• Prevalence of Alzheimer's:

  • Increases with age- For persons age 65 years, prevalence for men is 0.6% and women is 0.8%.

    • Increases to about one-fifth by age 90.

    • 40-60% of cases are moderate to severe.

    • Rates at age 85: 11% (men) and 14% (women).

    • Rates at age 90: 21% (men) and 25% (women).

    • Rates at age 95: 36% (men) and 41% (women).

  • Patients with Alzheimer's occupy over 50% of nursing home beds. More than 2 million persons with dementia live at home.

  • Predictions: 14 million Americans with Alzheimer's by 2050, and more than 18 million people with dementia.

• Vascular Dementia:

  • Second most common type, causally related to cerebrovascular diseases.

  • Hypertension predisposes individuals. Accounts for 15-30% of all dementia cases.

  • Most common in persons between ages 60 and 70, more common in men than women.

  • 10-15% of patients have coexisting vascular dementia and Alzheimer's.

• Other Causes:

  • Each representing 1-5% of all cases: head trauma, alcohol-related dementias, movement disorder-related dementias (Huntington's, Parkinson's).

• Dementia has many causes, necessitating a careful clinical workup.

• Etiology:

  • The most common causes of dementia in individuals older than 65 years of age are (1) Alzheimer disease, (2) vascular dementia, and (3) mixed vascular and Alzheimer disease.

  • Other illnesses that account for approximately 10% include Lewy body dementia, Pick disease, frontotemporal dementias, NPH, alcoholic dementia, infectious dementia, such as HIV or syphilis, and Parkinson disease.

• Many types of dementias evaluated in clinical settings can be attributable to reversible causes, such as metabolic abnormalities (e.g., hypothyroidism), nutritional deficiencies (e.g., vitamin B12 or folate deficiencies), or dementia syndrome caused by depression.

Alzheimer's Disease

• First described by Alois Alzheimer in 1907 in a 51-year-old woman with a 4½-year course of progressive dementia.

• Definitive diagnosis requires neuropathologic examination of the brain, but clinical diagnosis is possible after excluding other causes.

• Genetic Factors:

  • Researchers have progressed with understanding of amyloid deposits.

  • Up to 40% of patients have a family history of Alzheimer's, suggesting genetic involvement.

  • The concordance rate for monozygotic twins is higher than for dizygotic twins (43% vs. 8%).

  • Rare autosomal dominant transmission has been documented.

  • Alzheimer-type dementia has shown linkage to chromosomes 1, 14, and 21.

  • Amyloid Precursor Protein:

    • Gene for APP is on the long arm of chromosome 21. Differential splicing results in four forms of APP.

    • β/A4 protein, the principal constituent of senile plaques, is a 42-amino acid peptide and a breakdown product of APP.

    • Down syndrome (trisomy 21) has three copies of the APP gene.

    • Mutation at codon 717 in the APP gene results in excessive deposition of β/A4 protein.

  • Multiple E4 Genes:

    • People with one copy of gene E4 have Alzheimer's three times more frequently. P

    • eople with two E4 genes have the disease eight times more frequently than those with no E4 gene.

• Neuropathology:

  • Classic gross observation of an Alzheimer brain is diffuse atrophy with flattened cortical sulci and enlarged cerebral ventricles.

  • Pathognomonic microscopic findings are senile plaques, neurofibrillary tangles, neuronal loss (particularly in the cortex and hippocampus), synaptic loss (up to 50% in the cortex), and granulovascular degeneration of neurons.

• Neurofibrillary tangles composed of cytoskeletal elements, primarily phosphorylated tau protein (also occur in Down syndrome, dementia pugilistica, Parkinson-dementia complex of Guam, Hallervorden-Spatz disease, and healthy aging).

• Senile plaques, also referred to as amyloid plaques, more strongly indicate Alzheimer disease (also seen in Down syndrome and, to some extent, in healthy aging).

• Neurotransmitters:

  • Acetylcholine and norepinephrine are likely hypoactive in Alzheimer's.

  • Researchers hypothesize that degeneration of cholinergic neurons is present in the nucleus basalis of Meynert.

• Other Causes:

  • Abnormality in membrane phospholipid metabolism that results in rigid membranes may lead to the development of Alzheimer disease.

  • Excessive stimulation by the transmitter glutamate that may damage neurons.

Familial Multiple System Tauopathy with Presenile Dementia

• A recently discovered type of dementia, familial multiple system tauopathy, shares some brain abnormalities found in people with Alzheimer disease.

• The gene that causes the disorder is likely on chromosome 17.

• The symptoms of the disorder include short-term memory problems and difficulty maintaining balance and walking.

• The onset of the disease is in the 40s and 50s.

• Persons with the disease live an average of 11 years after the onset of symptoms.

• As in patients with Alzheimer disease, tau protein builds up in neurons and glial cells of persons with familial multiple system tauopathy.

• Eventually, the protein buildup kills brain cells.

• The disorder is not associated with the senile plaques seen with Alzheimer disease.

Vascular Dementia

• Vascular dementia is more common in men, especially those with preexisting hypertension or other cardiovascular risk factors.

• The disorder affects primarily small- and medium-sized cerebral vessels, which undergo infarction and produce multiple parenchymal lesions spread over wide areas of the brain.

• The causes of the infarctions can include occlusion of the vessels by arteriosclerotic plaques or thromobemboli from distant origins (e.g., heart valves).

• An examination of a patient may reveal carotid bruits, funduscopic abnormalities, or enlarged cardiac chambers.

• Binswanger Disease:is characterized by the presence of many small infarctions of the white matter that spare the cortical regions previously considered a rare condition.

Frontotemporal Dementia (Pick Disease)

• In contrast to the parietal–temporal distribution of pathologic findings in Alzheimer disease, Pick disease is a preponderance of atrophy in the frontotemporal regions.

• These regions also have neuronal loss, gliosis, and neuronal Pick bodies, which are masses of cytoskeletal elements.

• Pick bodies are seen in some postmortem specimens but are not necessary for the diagnosis.

• The cause of Pick disease is unknown.

• Characterized by personality and behavioral changes, with relative preservation of other cognitive functions, and it typically begins before 75 years of age.

Lewy Body Disease

• Lewy body disease is clinically similar to Alzheimer disease.

• However, it commonly presents with hallucinations, parkinsonian features, and extrapyramidal signs.

• Lewy inclusion bodies are in the cerebral cortex (Fig. 3-5).

• The exact incidence is unknown.

• These patients often have Capgras syndrome (reduplicative paramnesia) as part of the clinical picture.

Huntington and Parkinson Disease

• Huntingtons and Parkinson both affect the basal ganglia, commonly associated with dementia and depression.

• Psychomotor slowing and difficulty with complex tasks affect Huntington Disease but memory, language, and insight remain relatively intact in the early and middle stages of the illness. 20-30% of patients with Parkinson also have dementia.

HIV-Related Dementia

• Encephalopathy in HIV infection is associated with dementia and is called acquired immune deficiency syndrome (AIDS) dementia complex, or HIV dementia.

• Patients infected with HIV experience dementia at an annual rate of approximately 14 percent.

• An estimated 75 percent of patients with AIDS have involvement of the CNS at the time of autopsy.

• The development of dementia in people infected with HIV parallels the appearance of parenchymal abnormalities in MRI scans.

• Cryptococcus or Treponema pallidum can cause other infectious dementias.

Head Trauma-Related Dementia

• Can be a sequela of head trauma. the symptoms include emotional lability, dysarthria, and impulsivity. the S(punch-drunk syndrome (dementia pugilistica) occurs in boxers after repeated head trauma over many years. It also occurs in professional football players who developed dementia after repeated concussions over many years. Mrs. S, 75 years of age, was brought to the emergency department after being found wandering her neighborhood in a confused and disoriented state.

Amnestic Disorders due to Another Medical Condition

• Amnestic disorders primarily impair memory, though other cognitive declines may occur.

• The Synopsis authors find amnestic disorder a clinically useful term, but DSM-5 codes it as a neurocognitive disorder due to another medical condition.

• The core deficit is the inability to create new memories.

• Three etiologies:

  • Caused by a general medical condition (e.g., head trauma).

  • Substance-induced persisting amnestic disorder (e.g., carbon monoxide poisoning, chronic alcohol consumption).

  • Amnestic disorder not otherwise specified (etiology unclear).

Diagnosis

• Impairment in learning new information or recalling previously learned information.

• Significant impairment in social or occupational functioning.

• Caused by a general medical condition (including physical trauma).

• May be transient (hours or days) or chronic (weeks or months).

• Substance-Induced Persisting Amnestic Disorder:

  • Symptoms causally related to substance use.

  • DSM-5 refers to specific substance-related disorders: alcohol-induced, sedative/hypnotic/anxiolytic-induced, or other/unknown substance-induced.

Clinical Features and Subtypes

• Central Symptom: Memory disorder

  • Anterograde amnesia: Inability to learn new information.

  • Retrograde amnesia: Inability to recall previously remembered knowledge.

  • Results in significant social or occupational problems.

• Amnesia can begin at the point of trauma or include a period before the trauma.

• Memory loss can occur during the physical insult itself (e.g., cerebrovascular event).

• Short-term and recent memory is usually impaired.

  • Patients struggle to remember recent events, like what they ate or where they are.

• Orientation to person is usually preserved, but orientation to place and time may be lost.

• Remote events/overlearned information usually remain intact.

• Immediate memory (e.g., repeating six numbers) remains intact.

• Improvement may involve a gradual shrinking of the time with memory loss or gradual overall memory improvement.

• Onset can be sudden (trauma, cerebrovascular events, neurotoxic chemicals) or gradual (nutritional deficiency, cerebral tumors).

• Amnesia can be of short duration.

• Other cognitive impairments suggest dementia or delirium rather than isolated amnestic disorder.

• Subtle or gross personality changes can occur, such as apathy, lack of initiative, agitation, or excessive friendliness.

• Patients may appear bewildered, confused, and confabulate to cover their confusion.

• Patients typically lack insight into their neuropsychiatric condition.

Cerebrovascular Diseases

• Posterior cerebral and basilar arteries, and their branches, affect the hippocampus.

• Infarctions rarely limited to hippocampus; often involve occipital or parietal lobes.

• Common symptoms: focal neurologic signs involving vision or sensory modalities.

• Bilateral medial thalamus involvement associated with amnestic disorders.

• Rupture of anterior communicating artery aneurysm can cause infarction of basal forebrain, leading to amnestic disorders.

Multiple Sclerosis

• Plaques in brain parenchyma, particularly temporal lobe and diencephalic regions, can cause memory impairment.

• Memory impairment occurs in 40-60% of patients.

• Digit span memory is typically normal.

• Immediate and delayed recall are impaired.

• Memory impairment can affect verbal and nonverbal material.

Korsakoff Syndrome

• Amnestic syndrome caused by thiamine deficiency.

• Commonly associated with chronic alcohol use disorder.

• Other causes: starvation, gastric carcinoma, hemodialysis, hyperemesis gravidarum, prolonged IV hyperalimentation, gastric plication.

• Often associated with Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia).

• Neuropathologic findings: hyperplasia of small blood vessels, hemorrhages, hypertrophy of astrocytes, subtle changes in neuronal axons.

• Amnestic syndrome accompanies or follows untreated Wernicke encephalopathy in approximately 85% of cases.

• Patients display lack of initiative, diminished spontaneity, and lack of interest/concern (frontal lobe-like changes).

• Executive function deficits on neuropsychological tasks (attention, planning, set-shifting, inferential reasoning) consistent with frontal pattern injuries.

• Not a pure memory disorder, but a paradigm for amnestic syndrome presentations.

• Onset can be gradual.

• Recent memory more affected than remote memory, but this is variable.

• Confabulation, apathy, and passivity are often prominent.

• Treatment (thiamine) may prevent additional symptoms but seldom reverses severe amnestic symptoms.

• Approximately 1/3 to 1/4 of patients recover completely, and approximately 1/4 show no improvement.

Alcoholic Blackouts

• Persons with severe alcohol abuse may experience alcoholic blackouts.

• Awareness of being unable to remember a period during intoxication.

• Specific behaviors (hiding money, provoking fights) may be associated with blackouts.

Electroconvulsive Therapy (ECT)

• Associated with retrograde amnesia for several minutes before treatment and anterograde amnesia after treatment.

• Anterograde amnesia usually resolves within 5 hours.

• Mild memory deficits may remain for 1 to 2 months after a course of ECT.

• Symptoms resolve entirely 6 to 9 months after treatment.

Head Injury

• Can result in dementia, depression, personality changes, and amnestic disorders.

• Amnestic disorders commonly associated with retrograde amnesia leading up to the traumatic incident and amnesia for the incident itself.

• Severity of brain injury correlates with the duration and severity of the amnestic syndrome.

• Best correlate of eventual improvement: degree of clinical improvement in amnesia during the first week after regaining consciousness.

Transient Global Amnesia

• Abrupt loss of the ability to recall recent events or remember new information.

• Mild confusion and lack of insight.

• Clear sensorium.

• Occasionally, inability to perform some well-learned complex tasks.

• Episodes last from 6 to 24 hours.

• Incidence: 5-10 cases per 100,000 persons per year; for patients older than 50, as high as 30 cases per 100,000 persons per year.

• Pathophysiology is unknown, but it likely involves ischemia of temporal lobe and diencephalic brain regions.

• SPECT studies show decreased blood flow in temporal and parietotemporal regions, particularly in the left hemisphere.

• Almost universally complete improvement.

• Approximately 20% may have a recurrence, and approximately 7% may have epilepsy.

• Fewer patients have diabetes, hypercholesterolemia, and hypertriglyceridemia, but more have hypertension and migrainous episodes compared to TIAs.

Pathology and Laboratory Examination

• Quantitative neuropsychological testing can aid diagnosis.

• Standardized tests assess recall of well-known events/figures.

• Performance varies among individuals with amnestic disorder.

• Subtle deficits in other cognitive functions may occur.

• Memory deficits predominate in the mental status examination.

• No specific diagnostic features detectable on imaging studies (MRI, CT).

• Damage of midtemporal lobe structures is typical (enlargement of the third ventricle or temporal horns or structural atrophy).

Differential Diagnosis

• Obtain patient history, complete physical examination, and appropriate lab tests.

Dementia and Delirium

• Distinguished from delirium by the absence of disturbance of consciousness and preservation of other cognitive domains.

Normal Aging

• Minor memory impairment may accompany healthy aging.

• Diagnosis requires significant impairment in social or occupational functioning to exclude normal aging.

Dissociative Disorders

• Patients more likely to have lost orientation to self.

• May have more selective memory deficits.

• Often associated with emotionally stressful life events.

Factitious Disorders

• Inconsistent results on memory tests.

• No evidence of identifiable cause.

• Evidence of primary or secondary gain.

Course and Prognosis

• Depends on etiology and treatment.

• Generally, a static course with little improvement or progression.

• Exceptions: acute amnesias (transient global amnesia) and head trauma (improves steadily).

• Amnesia secondary to brain tissue destruction (stroke, tumor, infection) is irreversible but static once the disease process is halted.

Treatment

• Primary approach: treat the underlying cause.

• Supportive prompts regarding date, time, and location can reduce anxiety.

• Psychotherapy (cognitive, psychodynamic, or supportive) may help patients incorporate the amnestic experience into their lives.

Psychotherapy

• Psychodynamic interventions may be of value for brain insults.

• First phase: clinicians are a supportive auxiliary ego.

• Second phase: patients become angry and feel victimized; clinicians must contain projections.

• Third phase: integrative; clinicians help patients form a new identity and grieve lost faculties.

• Denial is common; clinicians must be sensitive and avoid blunt confrontations.

• Help patients accept cognitive limitations bit by bit.

• Help patients forgive themselves and others involved.

• Evaluate preexisting personality disorders.

• Cognitive rehabilitation centers promote recovery from brain injury.

Epidemiology

• No adequate studies report on incidence or prevalence.

• Most likely to see with alcohol use disorders and head injury.

• Frequency related to chronic alcohol abuse has decreased and frequency related to head trauma has increased.

Etiology

• Major neuroanatomical structures: diencephalic (thalamus), midtemporal lobe (hippocampus, mamillary bodies, amygdala).

• Usually results from bilateral damage, but some cases involve unilateral damage.

• Left hemisphere may be more critical than the right.

• Frontal lobe involvement can result in confabulation and apathy.

• Potential causes:

  • Thiamine deficiency, hypoglycemia, hypoxia (including carbon monoxide poisoning), and herpes simplex encephalitis damage the temporal lobes.

  • Tumors, cerebrovascular diseases, surgical procedures, or multiple sclerosis plaques involve the diencephalic or temporal regions.

  • Seizures, ECT, and head trauma.

  • Transient global amnesia is presumed to be a cerebrovascular disorder involving transient impairment in blood flow through the vertebrobasilar arteries.

• Many drugs, including nonprescription drugs, are associated with amnesia.

  • Benzodiazepines, especially with alcohol.

  • Triazolam can cause anterograde amnesia at higher doses or when combined with alcohol.

Neurocognitive and Other Psychiatric Disorders due to a General Medical Condition

• Mental disorders ultimately share an aberration in brain function.

• Differential diagnosis should include general medical conditions and substance use.

• Medical conditions can cause mental syndromes across the spectrum of diagnostic categories.

Epilepsy

• Most common chronic neurologic disease; affects approximately 1% of the U.S. population.

• Psychiatric concerns: epileptic diagnosis in psychiatric patients, psychosocial ramifications, and psychological/cognitive effects of anticonvulsants.

• 30-50% of persons with epilepsy have psychiatric difficulties.

• Most common behavioral symptom: change in personality.

• Psychosis and violence are less common than previously believed.

Definitions

• Seizure: transient paroxysmal pathophysiologic disturbance of cerebral function caused by a spontaneous, excessive discharge of neurons.

• Epilepsy: chronic condition characterized by recurrent seizures.

• Ictus (ictal event): the seizure itself.

• Nonictal periods: preictal, postictal, and interictal periods.

• Ictal symptoms depend on the brain origin and spread of activity.

• Ictal event influences interictal symptoms, as do other neuropsychiatric/psychosocial factors.

Classification

• Two major categories: partial and generalized.

  • Partial seizures: involve epileptiform activity in localized brain regions.

  • Generalized seizures: involve the entire brain.

Generalized Seizures

• Generalized Tonic-Clonic Seizures:

  • Loss of consciousness, generalized tonic-clonic movements, tongue biting, and incontinence.

  • Postictal state characterized by a slow, gradual recovery of consciousness and cognition.

  • Recovery ranges from minutes to hours; presents as a gradually clearing delirium.

  • Psychiatric problems involve helping patients adjust to a chronic neurologic disorder and assessing the cognitive/behavioral effects of anticonvulsant drugs.

• Absence Seizure (Petit Mal):

  • Brief disruptions of consciousness without convulsive movements.

  • Begins in childhood (5-7 years) and typically ceases by puberty.

  • EEG produces a characteristic pattern of three-per-second spike-and-wave activity.

  • Adult-onset can present as sudden, recurrent psychotic episodes or deliriums.

  • Symptoms may include a history of falling or fainting spells.

Partial Seizures

• Simple (without alterations in consciousness) or complex (with an alteration in consciousness).

• Complex partial seizures also known as temporal lobe epilepsy, psychomotor seizures, and limbic epilepsy.

• Affect approximately 3 of 1,000 persons.

• About 30% of patients have a major mental illness, such as depression.

Preictal Symptoms (Auras)

• Autonomic sensations (fullness in the stomach, blushing, changes in respiration).

• Cognitive sensations (déjà vu, jamais vu, forced thinking, dreamy states).

• Affective states (fear, panic, depression, elation).

• Automatisms (lip-smacking, rubbing, chewing).

Ictal Symptoms

• Brief, disorganized, and uninhibited behavior.

• Rarely organized, directed violent behavior.

• Cognitive symptoms include amnesia for the time during the seizure and resolving delirium after the seizure.

• Seizure focus can be found on EEG in 25-50% of patients.

• Multiple normal EEGs do not exclude a complex partial epilepsy diagnosis.

• Long-term EEG recordings (24 to 72 hours) can help detect a seizure focus.

Interictal Symptoms

• Personality Disorders.

• Most frequent psychiatric abnormalities reported in patients with epilepsy of temporal lobe origin.

• Common features: religiosity, heightened experience of emotions, and changes in sexual behavior.

• Relatively rare in its complete form.

• Striking religiosity: increased participation in religious activities, concern for moral and ethical issues, preoccupation with right and wrong, and interest in global and philosophical concerns.

• Viscosity of personality: conversation is slow, serious, ponderous, pedantic, overly replete with nonessential details, and often circumstantial.

• Hypergraphia: speech tendencies mirrored in writing; considered virtually pathognomonic for complex partial epilepsy.

• Changes in sexual behavior: hypersexuality, deviations in sexual interest, such as fetishism and transvestism, and, most commonly, hyposexuality.

• Psychotic Symptoms

• Interictal psychotic states are more common than ictal psychoses.

• Schizophrenia-like interictal episodes can occur.

• Estimated 10% of patients with complex partial epilepsy have psychotic symptoms.

• Risk factors include female gender, left-handedness, the onset of seizures during puberty, and a left-sided lesion.

• Psychotic symptoms classically appear after a long duration of epilepsy and personality changes.

• Most characteristic symptoms are hallucinations and paranoid delusions.

• Patients usually remain warm and appropriate in affect.

• Thought disorder symptoms involve conceptualization and circumstantiality.

• Violence

• Episodic violence has been a problem in some patients with epilepsy, especially epilepsy of temporal and frontal lobe origin.

• The extreme rarity of violence as an ictal phenomenon.

• Mood Disorder Symptoms

• Less common than schizophrenia-like symptoms.

• Tend to be episodic and appear most often when epileptic foci affect the temporal lobe of the nondominant cerebral hemisphere.

Diagnosis

• Maintain a high level of suspicion.

• Consider the possibility of an epileptic disorder even in the absence of classic signs and symptoms.

• Another differential diagnosis to consider is psychogenic nonepileptic seizures (previously called pseudoseizures).

• Consider the appearance of new psychiatric symptoms as possibly representing an evolution in their epileptic symptoms.

• Evaluate patient's compliance with the anticonvulsant drug regimen.

• Obtain results of one or more EEG examinations.

• Four characteristics should be cause for clinician to be suspicious of the possibility of epilepsy:

• Abrupt onset of psychosis in a person previously regarded as psychologically healthy

• Abrupt onset of delirium without a recognized cause

• A history of similar episodes with an abrupt onset and spontaneous recovery

• A history of previous unexplained falling or fainting spells

Treatment

• First-line drugs for generalized tonic–clonic seizures are valproate and phenytoin.

• First-line drugs for partial seizures include carbamazepine, oxcarbazepine, and phenytoin.

• Ethosuximide and valproate are first-line drugs for absence (petit mal) seizures.

• Carbamazepine and valproic acid may help control the symptoms of irritability and outbursts of aggression, as do the typical antipsychotic drugs.

• Psychotherapy, family counseling, and group therapy may be useful.

• Clinicians should be aware that many antiepileptic drugs cause mild to moderate cognitive impairment.

Brain Tumors

• Can cause virtually any psychiatric symptom or syndrome.

• Tumors cause fewer signs/symptoms than cerebrovascular diseases.

Clinical Features, Course, and Prognosis

• Mental symptoms occur in approximately 50% of patients with brain tumors.

• Tumors in frontal or limbic brain regions account for 80% of mental symptoms.

• Meningiomas cause focal symptoms by compressing a limited region of the cortex, gliomas are likely to cause diffuse symptoms.

Cognition

• Impaired intellectual functioning often accompanies the presence of a brain tumor, regardless of its type or location.

Language Skills

• Disorders of language function may be severe, mainly if tumor growth is rapid.

Memory

• Memory loss is a frequent symptom of brain tumors.

• Patients with brain tumors exhibit an amnestic syndrome and retain no memory of events that occurred since the illness began.

Perception

• Prominent perceptual defects are often associated with behavioral disorders.

Awareness

• Alterations of consciousness are common late symptoms of increased intracranial pressure caused by a brain tumor.

• Tumors arising in the upper part of the brainstem can produce akinetic mutism.

Colloid Cysts

• Colloid cysts located in the third ventricle can exert physical pressure on structures within the diencephalon and produce such mental symptoms as depression, emotional lability, psychotic symptoms, and personality changes.

• Classic associated neurologic symptoms are position-dependent intermittent headaches.

Head Trauma

• Can result in dementia due to head trauma or to mental disorder not otherwise specified due to a general medical condition (e.g., postconcussional disorder).

Pathophysiology

• Common clinical situation; an estimated 2 million incidents involve head trauma each year.

• Most commonly occurs in people 15 to 25 years of age and has a male-to-female predominance of approximately 3 to 1.

• Gross estimates based on the severity of the head trauma suggest that virtually all patients with severe head trauma, more than half of patients with moderate head trauma, and about 10 percent of patients with mild head trauma have ongoing neuropsychiatric sequelae resulting from the head trauma.

• Head trauma can be divided grossly into penetrating head trauma (e.g., trauma produced by a bullet) and blunt trauma, in which there is no physical penetration of the skull. Blunt trauma is far more common than penetrating head trauma.

• Motor vehicle accidents account for more than half of all the incidents of blunt CNS trauma; falls, violence, and sports-related head trauma account for most of the remaining cases

Symptoms

• Cognitive impairments: decreased speed in information processing, decreased attention, increased distractibility, deficits in problem-solving and in the ability to sustain an effort, and problems with memory and learning new information.

• Behavioral sequelae: depression, increased impulsivity, increased aggression, and changes in personality.

Treatment

• Initiate treatment with psychiatric agents in lower dosages than usual, and they should be titrated upward more slowly than usual.

Demyelinating Disorders

• Include multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), metachromatic leukodystrophy, adrenoleukodystrophy, gangliosidoses, subacute sclerosing panencephalitis, and Kufs disease.

• All can be associated with neurologic, cognitive, and behavioral symptoms.

Multiple Sclerosis

• Consists of multiple episodes of symptoms related to multifocal lesions in the white matter of the CNS.

• Estimated prevalence of MS in the Western Hemisphere is 50 per 100,000 people.

• The disease is much more frequent in cold and temperate climates than in the tropics and subtropics and more common in women than in men.

• The onset occurs between the ages of 20 and 40 years.

• Neuropsychiatric Symptoms: cognitive and behavioral.

• Although evidence indicates that patients with MS experience a decline in their general intelligence, memory is the most commonly affected cognitive function.

• The behavioral symptoms associated with MS are varied and can include euphoria, depression, and personality changes.

• Depression, however, is common; it affects 25 to 50 percent of patients with MS and results in a higher rate of suicide than is seen in the general population.

• Personality changes are also frequent in patients with MS; they affect 20 to 40 percent of patients and often include irritability or apathy.

Amyotrophic Lateral Sclerosis

• ALS is a progressive, noninherited disease of asymmetrical muscle atrophy.

• It begins in adult life and progresses over months or years to involve all the striated muscles except the cardiac and ocular muscles.

• In addition to muscle atrophy, patients have signs of pyramidal tract involvement.

• The illness is rare and occurs in approximately 1.6 persons per 100,000 annually.

• A few patients have concomitant dementia.

• The disease progresses rapidly, and death generally occurs within 4 years of onset.

Infectious Diseases

Herpes Simplex Encephalitis

• Most common type of focal encephalitis and most commonly affects the frontal and temporal lobes.

• The symptoms often include anosmia, olfactory and gustatory hallucinations, and personality changes and can also involve bizarre or psychotic behaviors.

Rabies Encephalitis

• The incubation period for rabies ranges from 10 days to 1 year, after which symptoms of restlessness, overactivity, and agitation can develop.

Neurosyphilis

• Neurosyphilis (also known as general paresis) appears 10 to 15 years after the primary Treponema infection.

• Since the advent of penicillin, neurosyphilis has become a rare disorder, although AIDS is associated with reintroducing neurosyphilis into medical practice in some urban settings.

• Neurosyphilis generally affects the frontal lobes and results in personality changes, the development of poor judgment, irritability, and decreased care for self.

Chronic Meningitis

• Becoming more common than earlier because of the immunocompromised condition of people with AIDS.

• The usual causative agents are Mycobacterium tuberculosis, Cryptococcus spp., and Coccidioides spp.

• The usual symptoms are headache, memory impairment, confusion, and fever.

Lyme Disease

• Lyme disease is caused by infection with the spirochete Borrelia burgdorferi transmitted through the bite of the deer tick (Ixodes scapularis), which feeds on infected deer and mice.

• A characteristic bull’s eye rash occurs at the site of the tick bite followed shortly after that by flulike symptoms.

• Such patients may get an erroneous diagnosis of a primary depression rather than one secondary to the medical condition.

Prion Disease

• Group of related disorders caused by a transmissible infectious protein known as a prion.

• Included in this group are Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker disorder (GSS), fatal familial insomnia (FFI), and kuru.

Etiology

• Prions are mutated proteins generated from the human prion protein gene (PrP), located on the short arm of chromosome 20.

• Some mutations are both fully penetrant and autosomal dominant and account for inherited forms of prion disease.

Creutzfeldt–Jakob Disease

• Ranges from one to two cases per 1 million persons a year worldwide.

• Neuropsychiatric signs and symptoms consist of ataxia, chorea, strabismus, delirium, and dementia.

Immune Disorders

HIV Infection and AIDS

• HIV is a retrovirus related to the human T-cell leukemia viruses (HTLV) and to retroviruses that infect animals, including nonhuman primates.

• HIV- 1 is the causative agent for most HIV-related diseases; HIV-2, however, seems to be causing an increasing number of infections in Africa.

• The Centers for Disease Control and Prevention guidelines for the prevention of HIV from infected to uninfected persons

  • Protecting a partner during any sexual activity by taking appropriate precautions

  • For IV drug abusers, enrolling or continuing in programs to eliminate the abuse of IV substances

Clinical Features

• The most common infection in persons affected with HIV who have AIDS is Pneumocystis carinii pneumonia, which is characterized by a chronic, nonproductive cough and dyspnea

Treatment

• Antiretroviral agents have many adverse effects. We should take caution when prescribing psychiatric drugs to persons taking protease inhibitors.

• Individual therapy may be either short term or long term and may be supportive, cognitive, behavioral, or psychodynamic.

Autoimmune Receptor-Seeking Disorders

• A group of autoimmune receptor-seeking disorders exists that causes encephalitis that mimics schizophrenia.

• Among those is anti-NMDA (N-methyl D-aspartate)-receptor encephalitis that causes dissociative symptoms, amnesia, and vivid hallucinations.

Endocrine Disorders

Thyroid Disorders

• Serious psychiatric symptoms include impairments in memory, orientation, and judgment, manic excitement, delusions, and hallucinations.

Parathyroid Disorders

• Dysfunction of the parathyroid gland results in the abnormal regulation of calcium metabolism.

Adrenal Disorders

• Excessive quantities of cortisol produced endogenously by an adrenocortical tumor or hyperplasia (Cushing syndrome) lead to a secondary mood disorder, a syndrome of agitated depression, and often suicide.

  Metabolic Disorders

Hepatic Encephalopathy

• Severe hepatic failure can result in hepatic encephalopathy, characterized by asterixis, hyperventilation, EEG abnormalities, and alterations in consciousness.

Hypoglycemic Encephalopathy

• Hypoglycemic encephalopathy can be caused either by excessive endogenous production of insulin or by excessive exogenous insulin administration.

Acute Intermittent Porphyria

• The porphyrias are disorders of heme biosynthesis that result in excessive accumulation of porphyrins.

Nutritional Disorders

Thiamine Deficiency

Cobalamin Deficiency

• Deficiencies in cobalamin (vitamin B12) arise because of the failure of the gastric mucosal cells to secrete a specific substance, intrinsic factor, required for the normal absorption of vitamin B12 in the ileum.

Toxins

• Environmental toxins are becoming an increasingly severe threat to physical and mental health in contemporary society.

Mercury

• Inorganic mercury poisoning results in the “mad hatter” syndrome, with depression, irritability, and psychosis.

• Associated neurologic symptoms are headache, tremor, and weakness.

Lead

• Lead poisoning occurs when the amount of lead ingested exceeds the body’s ability to eliminate it.

Manganese

• Early manganese poisoning (sometimes called manganese madness) causes symptoms of headache, irritability, joint pains, and somnolence.

Arsenic

• Chronic arsenic poisoning most commonly results from prolonged exposure to herbicides containing arsenic or from drinking water contaminated with arsenic.

Mild Cognitive Impairment

• Mild cognitive decline not warranting the diagnosis of dementia but with preserved basic activities of daily living.

Definition

• Proposed by the Mayo Clinic Alzheimer’s Disease Research Center:

  1. Memory complaint

  2. Memory impairment for age and education

  3. Preserved general cognitive function

  4. Intact activities of daily living

  5. Not demented

Clinical Presentation

• The clinical picture of MCI is a function of the criteria used to define it. Memory impairment is necessary but has been challenging to quantify.

Assessment

• Brief mental status instruments (e.g., the Mini-Mental State Examination) are relatively insensitive for the detection of memory problems in MCI.

Course and Prognosis

• Typical rate at which MCI patients progress to dementia of the Alzheimer type is 10-15% per year.

Treatment

• There are no FDA-approved treatments for MCI at this time.

Epidemiology and Etiology of MCI

• The recognition that Alzheimer disease pathology may exist in the brain long before the presence of clinical symptoms led to the focus on preclinical stages to characterize initial impairments that are associated with an increased risk of progression to Alzheimer disease.