Dementia

intellectual, loss, aphasia

Dementia

-Progressive impairment in ____________ function with ____ of memory and at least one other cognitive deficit like _______, apraxia, or agnosia 

progressive, delirium, aging, executive, loss, word, visuospatial

Clinical Presentation: Background

-___________ neurocognitive decline

-Rule out acute _________, normal ______, and pseudo dementia 

-________ dysfunction → easy distractibility, impulsivity, mental inflexibility, concrete thought, slowed processing speed, poor planning and organization, or impaired judgement

-Short-term memory ____

-Word-finding difficulty

-Apathy

-__________ dysfunction

-Apraxia

cognitive, mild, biased, impaired, quantifies

Neuropsychological Assessment

-Detecting _______ impairment → Folstein Mini MSE, mini-cog, Montreal Cognitive Assessment (MoCA)

-Important limitations of standard test → insensitive to ____ cognitive impairment, may be _______ negatively by the presence of language or attention problems, and don’t correlate with functional capacity 

-A neuropsychiatric evaluation to enhance localization by defining ________ cognitive domains, _________ the degree of impairment 

cognitive, B12, TSH, HIV

Diagnostic Testing

-Should be measured for any patient with _________ symptoms → serum levels of Vitamin ___, free T4 and TSH, CBC, CMP, lipid panel 

-Consider VRDL/RPR and ___ tests 

new, without, PET, specific, Alzheimer’s, beta-amyloid, decline

Diagnostic Imaging

-Indicated in any patient with a ___, progressive cognitive complaint → brain imaging with MRI/CT ________ contrast

-PET with FDG → doesn’t confirm or exclude any _______ cause of dementia. May be useful in discriminating _________’_ disease vs frontotemporal dementia

-PET imaging with radiolabeled ligand for ____-_______ is highly sensitive to amyloid pathology. May provide positive evidence for Alzheimer disease in a patient with cognitive _______

increasing, 65, younger

Alzheimer Disease (AD)

-Most common dementia, present in up to 50% of patients

-The greatest known risk factor is __________ age

• Majority of patients with Alzheimer’s under __ have younger-onset Alzheimer’s disease

-200,000 Americans under 65 have _______-onset Alzheimer Disease

-Etiology is not very clear, but there may be a family component

shrinkage, ventricles

Alzheimer’s Dementia: Pathophysiology, pt 1 

-__________ of cerebral cortex → temporal, frontal, parietal 

-Enlarged ___________ → hydrocephalus ex vacuo 

plaques, beta-amyloid, APP, between, signaling, angiopathy, fibers, tau, inside, apoptosis

Alzheimer’s Disease: Pathophysiology, Pt. 2

-________ and tangles damage and destroy nerve cells

• Plaques are deposits of a protein fragment called ____-______, which is a byproduct of ___ degradation.

• Builds up in the space ________ nerve cells, creating issues with neuron to neuron __________

• Builds up around brain vessels (amyloid _______)

-Tangles are twisted _______ of a protein called ___

• Builds up ______ cells

• Poor signaling within neuron → __________, for the neuron cannot compensate

remembering, newly, learning, entorhinal, temporal, hippocampus, neocortex, acetylcholine

Alzheimer Disease (AD)

-The most common early symptom of Alzheimer’s is difficulty ____________ _____ learned information

-Alzheimer changes typically begin in the part of the brain that affects _________

-Begins in the __________ region of the medial _______ lobe, spreading to the ____________ later on in progression

-Then moves to the lateral and posterior temporal and parietal _________, causing decreased ___________ neurotransmitter

disrupts, planning, confusion, speaking, decreased, mood

10 Early Signs of Alzheimer Disease

1. Memory loss that _______ daily life

2. Challenges in ________/solving problems 

3. Difficulty completing familiar tasks

4. ___________ with time/place 

5. Trouble understanding visual images/spatial relationships

6. New problems with words in __________/writing 

7. Misplacing things/can’t retrace steps 

8. __________/poor judgement 

9. Withdrawal from work/social activities 

10. Changes in ____ and personality 

disorientation, confusion, suspicions, loss, swallowing

Alzheimer Disease Progression

-As it advances through the brain, it leads to:

• ____________

• Mood/behavior changes

• Deepening __________ about events

• Time and place

• Unfounded ___________ about family, friends, and professional caregiver

• More serious memory ____ and behavior changes

• Difficulty speaking, ___________, and walking

Mild

What stage of Alzheimer’s is this?

-Problems coming up with the right word or name

-Trouble remembering names when introduced to new people

-Challenges performing tasks in social or work settings

-Forgetting material that one has just read

-Losing or misplacing a valuable object

-Increasing trouble with planning or organizing

Moderate

What stage of Alzheimer’s Disease is this?

-Forgetfulness of events or about one’s own personal history

-Feeling moody or withdrawn, especially in socially or mentally challenging situations

-Being unable to recall their own address or telephone number 

-Confusion about where they are or what day it is 

-The need for help choosing proper clothing

-Trouble controlling bladder and bowels 

-Changes in sleep patterns, such as sleeping during the day

-An increased risk of wandering and becoming lost

-Personality and behavioral changes 

Severe

What stage of Alzheimer’s Disease is this?

-Need round-the-clock assistance with daily activities and personal care

-Lose awareness of recent experiences as well as of their surroundings

-Experience changes in physical abilities

-Have increasing difficulty communicating

-Become vulnerable to infections

cholinesterase, progression, symptomatic, diarrhea, cardiac, EKG

Alzheimer Disease Treatment: First Line Therapy

-_____________ inhibitors are first-line therapy for Alzheimer’s disease

• Donepezil, rivastigmine, galantamine

-They do not prevent disease ______________

-Provide modest, ______________ treatment for cognitive dysfunction

-ADRs → nausea and ________ are common. Syncope and _______ dysrhythmia are uncommon but more serious. Order ___ before and after starting therapy in patients with cardiac disease or a history of syncope

Memantine, combination, neurons, vascular

Alzheimer Disease: Treatment

-_____________ → NMDA receptor antagonist that works well in _____________ with cholinesterase inhibitors 

-Moderate to severe disease → can restore physiologic function of _________ to improve symptoms, as well as protects from further damage (especially in __________ dementia)

amyloid, beta, mild, modest

Alzheimer Disease Treatment

-_________ targeted therapies → Lecanamab, Donanemab

-Recombinant monoclonal antibodies directed against amyloid ____

-Indicated only in patients with ____ cognitive impairment/mild dementia

-Efficacy is ______; need to weigh risks of ADR

E, functional, cognitive

Alzheimer’s Disease Treatment: Antioxidants

-Vitamin _ at a dose of 2000 IU per day confers a modest benefit in delaying __________ progression in patients with mild to moderate

-Selegiline has some benefit in the treatment of _________ benefits ± behavior and mood

admission, avoided, delirium

Dementia Patients Need to Stay Home

-_____________ to the hospital should be _________ due to increased risk of developing hospital-acquired __________

behavioral, Citalopram, Trazodone, antihistamines, apathy

Alzheimer Dementia: Treatment of Mood and Behavioral Disturbance

-Agitation

• ___________ interventions are the first line → reorientation and distraction from anxiety-provoking stimuli

• ____________ or low doses of an atypical antipsychotic → caution in patient’s with a fall risk

-Insomnia

• _____________ at bedtime prn

• Don’t use _____________ or benzodiazepine medications → can worsen cognition and precipitate delirium

-______

• Psychostimulants may help, but may also increase CV risk and agitation

post-stroke, speaking, headache, numbness

Vascular Dementia: Background

-Sudden ____-______ change in thinking and perception may include:

• Confusion

• Disorientation

• Trouble _________ or understanding speech

• Physical stroke symptoms (sudden _________)

• Difficulty walking

• Poor balance

• ___________ or paralysis on one side of the face or body

Asian, intracranial, increasing, hypertension

Vascular Dementia

-Vascular dementia is more common in _______ countries due to higher prevalence of ____________ atherosclerosis 

-Rates of vascular dementia are __________ in developing countries due to vascular risk factors like ____________, hypercholesterolemia, and diabetes mellitus 

underlying, Alzheimer’s

Vascular Dementia Management

-Treat the _________ disease → HTN, hyperlipidemia, or diabetes

-No drugs specifically for vascular dementia → _________’_ drugs do not show benefit

visual, Parkinsonism, rapid, sleepiness

Dementia with Lewy Bodies (DLB)

-______ hallucinations

-_____________

-Fluctuating alertness

-Neuroleptic sensitivity

-_____ eye movement (REM) sleep behavior disorder (RBD)

-Hyposomnia and excessive daytime ____________

-Delusions related to persecution, invasion, and person or place identity

brainstem, substantia, orthostatic, parkinsonism, intraneuronal, synuclein, PAS, antibodies

Dementia with Lewy Bodies: Pathophysiology

-Both PDD and DLB may be accompanied or preceded by symptoms referable to __________ pathology below the ________ nigra:

• Constipation, _________ lightheadedness (distinguish from __________ if present), depression/anxiety, and REM sleep behavior disorder 

-Neuropathy: Lewy bodies are ____________ cytoplasmic inclusions composed of abnormal a-__________ protein

• Intraneuronal cytoplasmic inclusions stain with periodic acid-Schiff (___)

• Now identified with __________ to the presynaptic protein, a-synuclein 

behavioral, Cholinesterase, parkinsonism, atypical, melatonin

Dementia with Lewy Bodies: Management

-Symptomatic management (no disease modifying effects)

• Start with __________ interventions

• ___________ inhibitors are first-line therapy

• ± Memantine

-Don’t use antipsychotics → exacerbation of __________, confusion

• If must be used only give _________ in tiny doses

-REM sleep disorder → low dose ________ or clonazepam

behavior, comprehending, memory, judgement, behavior

Frontotemporal Dementia: Background

-Younger patients (40-60 years)

-Deterioration in __________, personality, and/or difficulty with producing or ___________ language

-Less likely to begin with _______ problems

-More likely to present with difficulties with ___________, mood, executive control, movement, and __________

tau, TDP43

Frontotemporal Dementia: Etiology

-There are a number of different diseases that cause frontotemporal degenerations

-The two most prominent are:

• Group of brain disorders involving the protein ___

• Group of brain disorders involving the protein called _____

• These are why PET scans can be helpful 

behavior, SSRI, antipsychotic, cholinesterase

Frontotemporal Dementia Management

-No current FDA approved treatment

-________ therapy → speech and psychiatric behavior therapy

-Pharmacologic symptom management → ____ for behavior problems, atypical __________ for agitation

-____________ inhibitors are not given for frontotemporal dementia, for they may worsen behavioral symptoms

MDD, caudate, personality, progressive, HIV, liver

Additional Differential Diagnoses to Consider

-Pseudodementia → often co-existing ___

-Huntington’s Disease (______ degeneration) → progressive dementia with _________ changes and choreoathetosis

-Creutzfeldt-Jacob Disease → rapidly __________ dementia

-AIDS Dementia Complex → dementia and focal neurological symptom in ___+ person

-Wilson’s Disease → executive dementia with psychotic disturbances, movement disorder and _____ dysfunction

quickly, months, prion, Hashimoto, paraneoplastic 

Rapidly Progressive Dementia

-When dementia develops ________, with obvious decline over a few weeks to a few ______, we need to rule out the following:

• (1) _____ disease

• (2) Infection

• (3) Toxins

• (4) Neoplasms

• (5) Autoimmune/inflammatory disease → corticosteroid-response (__________) encephalopathy, antibody-mediated _____________ syndromes