Selected Major Neurocognitive Disorders

Definition: Major Neurocognitive Disorder (NCD)

Previously known as dementia, characterized by memory impairment and cognitive decline; A progressive cognitive decline that interferes with normal social and occupational functions, or with usual ADLs. Group of symptoms (not a disease) causing progressive decline in independence and functionality (decline in greater than or equal to 1 cognitive domain [learning and memory, executive function, complex attention, perceptual-motor, social cognition); Insidious onset; Non neurodegenerative major NCD may be reversible or halted/slowed (vacular); Major NCDs are often indistinguishable form AD and may coexist. May have >1 cause: mixed dementia

Most common causes of NCD are neurodegenerative:

Alzheimer’s disease (AD), frontotemporal, lewy body, parkinson’s disease

Epidemiology

39% of Americans >71 have major NCD; most have AD, accounts for 70% of all cases; >50% of Americans >90 years of age have a major NCD

Alzheimer’s disease prevalence

10.7%

Vascular NCD prevalence

2.4%

Lewy body dementia prevalence

0.1%

Frontotemperol prevalence

0.002%

HAND prevalence

2-14% of those w/HIV

Pathogenesis: Alzheimer’s Disease

Remains unknown; Genetic factors (Amyloid precursor protein, Multiple E4 genes); Neuropathy (diffuse atrophy, amyloid plaques, neurofibrillary tangles); Neurotransmitters (cholinergic deficit, decrease in somatostatin and corticotropin

Pathogenesis: Vascular

Multiple areas of cerebral vascular disease; Primarily small and medium sized vessels, Arterioslerotic plaques or thomboemboli occlude vessels; undergo infarction leading to multiple lesions over wide areas of the brain

Pathogenesis: lewy body

Similar to AD, lewy inclusion bodies in the cerebal cortex

Pathogenesis: Frontotemperol (Pick Disease)

Atrophy in frontal and temperal regions; Neuronal loss; Gliosis: fibrous proliferation of glial cells in injured areas of CNS; Neuronal “Pick bodies”: solitary, roung, argyrophilic inclusions found in the cytoplasm of neurons

Pathogenesis: HAND

Encephalopathy due to infections; Parenchymal abnormalities

Non modifiable risk factors

Age>65; family history; down syndrome; hx of delirium, stroke, neurologic disease, brain trauma; female

Modifiable Risk Factors

HTN, dyslipidemia; cardiovascular disease; peripheral atherosclerosis; Type 2 diabetes and obesity; Lack of physical activity; Brain trauma/head injury; Hearing loss; Depression; Sleep disturbances; Medications (benzodiazepines, anticholinergics, PPIs); Unhealthy diet; Vitamin and nutritional deficiencies (low vitamin D, B-6, B-12, and folate); Excessive alcohol use; Environmental factors (secondhand smoke, air pollution, pesticides)

Prognosis

Poor; Gradual deterioration over 5-10 years, leading eventually to death; Average survival expectation for those w/AD is 8 years (1-21); Mortality 2 times higher than non-demented patients; May be the leading cause of death in the near future

Psychiatric and Neurologic Changes

Personality changes; Hallucinations; Delusions; Mood (depression, anxiety); Cognitive changes (aphasias, apryexias, agnosias; seizures; difficulty abstracting, problem solving, reasoning logivally, making sound judgements), lack of judgement and poor impulse control; Sundowning

RBD

Parasomnia characterized by dream enactment behavior that emerges after a loss of the atonia that occurs in REM sleep. RBD is commonly associated with DLB, occurring in up to 90% of individuals

Clinical Manifestations: Alzheimer’s Disease

Memory impairment (most common initial symptom), declarative episodic memory, difficulty remembering recent conversations, names, or events. Impaired executive function/problem solving, loss of insight. Apathy, social disengagement, irritability, and depression are also often early symptoms. Later symptoms include impaired communication, disorientation, confusion, poor judgement, behavioral changes, and ultimately, difficulty speaking, swallowing, and walking

Clinical Manifestations: Vascular Dementia

Impaired executive function w/slowed thinking or impaired ability to make decisions, plan, or organize may be the initial symptoms. Memory can also be affected, especially when the brain changes of other causes of dementia are present. Depression, lack of motivation, apathy, psychosis w/delusions or hallucinations. Impaired motor function, slow gait and poor balance.

Clinical Manifestations: Lewy Body

Symptoms common in AD. Core clinical features: Cognitive fluctuations, visual hallucinations (up to 70% of patients), rapid eye movement (REM) sleep behavior disorder (RBD), and parkinsonism. Symptoms may differ dramatically hourly or from day to day. Postural instability and falls, transient, LOS, syncope, autonomic dysfunction, hypersomnia, hyposmia, elaborate, specific, and systemic delusions, apathy, anxiety, depression

Clinical Manifestations: Frontotemporal dementia

Behavioral variant: Marked changes in personality and behavior (early symptom) w/disinhibition, apathy, and loss of empathy, compulsive behaviors, decreased/loss of insight, and/or difficulty with producing or comprehending language. Unlike alzheimer’s, memory is typically spared in the early stages of disease. Primary progressive aphasia: Early, progressive, language disturbance, functional impairment, motor speech deficit, apraxia, social comportment, memory, visual spatial skills, and other cognitive abilities are typically preserved at the time of presentation. While patients usually retain some insight, they may seem inappropriately unconcerned.

Clinical Manifestations: HAND

Substantial memory deficits, impaired executive functioning, poor attention and concentration, mental slowing, and apathy. Lack of motivation, irritable mood, sleeplessness, weight loss, restlessness, and anxiety. Slowness of movement and giat. Impaired savcadic eye movements, marked difficulty with smooth limb movement (especially in the lower extremities), dysdiadochokinesia, hyperreflexia, and frontal release signs such as grasp, root, snout, and glabellar reflexes

Common Noncognitive Behavior Symptoms: Change in mood

Happens especially early, is frequent, examples are anxiety, depression, and mania

Common Noncognitive Behavior Symptoms: Changes in thinking

Early and late; happens frequently; examples suicidal ideation, delusions, hallucinations

Common Noncognitive Behavior Symptoms: changes in Activity

Early and late; happens frequently; Examples are apathy, agitation/aggression, wandering, disordered eating behavior, sexually inappropriate behavior, sleep/activity cycle disruption

Assessment of Major NCD

No simple reliable test for diagnosing dementia at an early stage; Thorough physical and neurological evaluation must be done; Evaluate mental status (short, long-term memory, problem solving, depression)

Initial Assessment

Conduct psychiatric evaluation with specific focus on: History, family member accounts, and functional status; Screening questions and screening tools: Montreal Cognitive Assessment (MOCA), PHQ-2; History of present illness, focus on: Family, friend, caretaker reports; Past medical history; Physical examination: neurological ecam, focus on parkinsonism (cogwheel rigidity tremors), gait abnormalities or slowing eye movements; Mental status exam: short and long term memory, problem solving, depression; Substance use/abuse, especially alcohol; Thorough medication review; Always assess for suicide ideation, plan, and intent

Diagnostic Workup: Physical and mental eval: Labs

CMP, CBC, UA w/culture; TSH; Vit D, B12, folate

Diagnostic Workup: Physical and mental eval: Neuroimaging

Obtain head CT or MRI for acute onset cognitive impairment or rapid neurological deterioration

DSM-5-TR criteria Major vs Minor NCG: Major: A and B

Significant cognitive decline in one or cognitive domains, based on: 1. concern about significant decline, expressed by individual or reliable informant, or observed by a clinician. 2. Substantial impairment, documented by objective cognitive assessment. B. Interference with independence in everyday activities

DSM-5-TR criteria Major vs Minor NCG: Mild: A and B

A. Modest cognitive decline in one or more cognitive domains based on: concerns about mild decline, expressed by individual or reliable informant, or observed by a clinician. 2. Modest impairment, documented by objective cognitive assessment. B. No interference with independence in everyday activities, although these activities may require more time and effort, accommodation, or compensatory strategies.

DSM-5-TR criteria Major and Minor NCG: C, D, E

C. Not exclusively during delirum. D. Not better explained by another mental disorder. E. Specify one or more etiologic subtypes “due to”: Alzheimer’s disease, Cerebrovascular disrder (Vascular Neurocognitive Disorder), Frontotemporarl Lobe Degeneration (Frontotemporal Neurocognitive Disorder); Dementia with Lewy Bodies (NCD with Lewy Bodies); Parkinson’s disease; Huntington’s disease; Traumatic brain injury; HIV infection; Prion disease; Another medical condition; Multiple etiologies

Differential Diagnosis

Delirium; Depression; Cerebrovascular accident (CVA); Structural brain pathology-tumor, malformation, subacute stroke; Obstructure sleep apnea; Thyroid disorders; Drug interactions or adverse effects; Schizophrenia

Prevention of Dementias: Modify risk factors: May prevent or delay up to 40% of dementia

Maintain systolic BP of 130< mmHG (antihypertensive treatment for HTN is the only known effective preventive medication for dementia); Encourage use of hearing aids for hearing loss, reduce hearing loss by protection of ears from excessive noise exposure; Reduce exposure to air pollution and second-hand tobacco smoke; Prevent head injury; Limit alcohol use: <10 drinks/week for females and <15 drinks/week for males; Avoid smoking uptake and support smoking cessation to stop smoking; Reduce exposure to air pollution, such as exhaust from heavy traffic; Reduce obesity and the linked condition of diabetes; Make healthy food choices: Mediterranean diet; Sustain midlife and later life physical activity; Correct sleep; Stay socially connected; Reduce stress; Treat depression

Non-pharmacologic treatment

Support caregiver and support family in realistic goal setting; maintain functional ability; pet therapy; music; aromatherapy (lemon balm or lavender); calm, slow approaches, well-lit areas w/out shadows; Ongoing assessment of capacity; Advance care planning: start early; Address safety: driving, falls, wandering, becoming lost, cooking

APA new guideline on antipsychotics in dementia-2016:

Antipsychotics when agitation and/or psychosis “is severe, dangerous, and/or causing signifiant distress to the patient”; Best evidence: modest support- risperidone for psychosis/agitation and olanzapine/aripiprazole for agitation

Pharmacologic Treatment: Cognitive Enhancers: Cholinesterase Inhibitors can delay onset of NCBS, but:

Common: GI symptoms, insomnia, vivid dreams, fatigue, increased urination, cramps; Uncommon: syncope, bradycardia, confusion, depression, agitation, GI bleed; Caution with liver/gastric disease, COPD, bradycardia, sick sinus sydnrome, inadequate supervision

Pharmacologic Treatment: Cognitive Enhancers: Memantine can mildly reduce agitation for some, but:

more common: headache, constipation; uncommon: confusion; agitation can occur early, but is infrequent

Pharmacologic Treatment: Cognitive Enhancers: Cholinesterase inhibitors meds: Specific agents

Donepezil, Rivastigmine, Galantamine ER

Pharmacologic Treatment: Cognitive Enhancers: Cholinesterase inhibitors meds: Evidence says

Modest benefits in cognition, ADLs, caregiver burden, questionable benefits for NCBS

Pharmacologic Treatment: Cognitive Enhancers: NMDA receptor antagonist: specific agents

Nameda (memantine) or Namenda XR

Pharmacologic Treatment: Cognitive Enhancers: NMDA receptor antagonist: Evidence says

Modest benefits in cognition, ADLs, caregiver burden, possible mild benefit for NCBS

Medications with evicence of benefit for NPS of MNCD

Citalopram (5-10 mg); Risperidone (0.25 mg to 1 mg); Olanzapine (1.25-5 to 10 mg); Aripiprazole (5 mg to 15 mg); Haloperidol (0.25-0.5 mg to 2 mg); Donepezil (5 mg to 10 mg); Memantine monotherapy (10 mg) memantine + donepezil (5 mg TID)

Medications: Typical Antipsyhotics: syndromes

psychosis, agitation, aggression

Medications: Typical Antipsyhotics: usual agents

haloperidol, perphenazine, trifluoperazine

Medications: Typical Antipsyhotics: Evidence says

Not safer or better than atypicals -EPS including TD, sedation, weight, anticholinergic, hypotension, less metabolic syndrome, no less mortality

Medications: Typical Antipsyhotics: suggested use

0.5 to 2 mg/d can be used for acute sedation; not recommended

Medications: Atypical Antipsychotics:Syndromes

Psychosis, agitation, aggression

Medications: Typical Antipsyhotics: Aripiprazole

May have modest benefit for agitation/pschosis; begin with 2 mg/d increase as high as 10 mg/d

Medications: Typical Antipsyhotics: Risperidone

May have modest benefit for agitation/psychosis; begin with 0.25 mg/d; increase as high as 2 mg/d

Medications: Typical Antipsyhotics: Quetiapine

Questionable evidence; begin with 12.5 mg/d; increase as high as 200 mg/d

Medications: Typical Antipsyhotics: Olanzapine

Questionable; begin with 2.5 mg/d increase as high as 15 mg/d

Medications: Typical Antipsyhotics: brexpiprazole

Investigational evidence; 0.5-2 mg/d in testing

Medications: Typical Antipsyhotics: Clozapine

Inadequate data; begin with 6.25 mg/d; increase up to 300 mg/d

Medications: Antidepressants