MCI and Alzheimer's Disease Flashcards
Alzheimer’s disease (AD)
progressive, degenerative brain disorder with no known cure that results in generalized cerebrocortical dysfunction and dementia, typically characterized by anterograde amnesia that is eventually accompanied by other cognitive deficits (language, executive function/attention, processing speed, and visuospatial skills)
- neuropsychological deficits must reflect a significant decline from premorbid functioning and interfere with an individual’s ability to perform ADLs
Mild cognitive impairment (MCI)
considered a prodromal phase prior to AD onset
consists of relatively isolated cognitive impairment beyond that seen in normal aging.
Do not drastically interfere with individuals ADLs
Mild Cognitive Impairment (MCI) Classifications
Amnestic MCI, Single Domain - Most common presentation and most likely to progress to AD;
focal memory impairment (verbal episodic memory usually affected first) in the absence of other gross cognitive impairments
Amnestic MCI, Multiple Domain - Impairment in memory plus at least one other cognitive domain
such as language, executive function, or visuospatial skills
Non-Amnestic MCI, Single Domain - Impairment in a cognitive domain other than memory, such as
executive function, visuospatial processing, or language.
Non-Amnestic MCI, Multiple
Domain - Impairment in several cognitive domains other than memory, but not to the extent that meets criteria for dementia.
Diagnostic classification/billing classification term for Mild cognitive impairment (MCI)
mild neurocognitive disorder
biomarker classification system of Alzheimer’s disease
collectively referred to as the
“AT(N)” (amyloid, tau, neurodegeneration) system
amyloid, tau, and other measures of neurodegeneration (i.e., currently based upon structural MRI, PET, and/or CSF amyloid/tau)
Alzheimer’s neuropathology
The lesions of AD consist of synaptic and neuronal loss associated with:
- progressive deposition of amyloid in the form of diffuse neuritic plaques,
- accumulation of tau in the form of neurofibrillary tangles and neuropil threads.
Follows a temporal-to-frontal spread and eventually involves multiple brain systems
- hippocampus and entorhinal
cortex are implicated in the early stage of the disease temporal lobe and association areas where most atrophy occurs in many cases
Primary motor, visual, auditory, and somatosensory cortices, as well as aspects of subcortical structures, tend to be relatively unaffected until quite late in the disease process.
Alzheimer’s risk factors
- Age (typically over 65) is the single largest known risk factor for AD.
- first-degree family
member with AD increases risk - Early-onset familial AD has been implicated with a mutation in identified genes on chromosomes 1 (Presenilin
2 gene), 14 (Presenilin 1 gene), and 21 (APP gene). - poorly controlled diabetes
- moderate to severe traumatic brain injury
Age of Alzheimer’s diagnosis
average age at diagnosis is
approximately 75 years
up to 50% of individuals over age 85 meet criteria for AD
While less common, AD can occur in much younger individuals, sometimes with an onset between age 50 and 65.
<5% of patients with AD are believed to have a familial variant of the disease, which have early-onset (40-60 age) and have more rapid decline
Diagnosis of Alzheimer’s requires:
MRI (or PET, which helps differentiate AD from FTD) biomarker/blood chemistry
neurologic exam neuropsychological evaluation clinical history
Cognitive abilities typically resistant to aging
- vocabulary and verbal skills; reading ability
- simple attention and concentration
- basic arithmetic problem solving
- recognition memory and recall of the gist of stories
- remote memory (i.e., recall from many years ago)
Stages of Alzheimer’s Disease
- Prestage: Mild Cognitive Impairment
- four subtypes, do not interfere with ADLs (MCI to dementia ~10%/year) - Stage 1 (1-3 years): Memory impairment, dysnomia/word finding and naming difficulties, lack of awareness
- may develop symptoms of depression or anxiety - Stage 2 (2-10 years): Amnesia, aphasia, visuospatial deficits, personality/emotional changes
- increasing poor episodic memory and rapid forgetting but intact remote memory
- misplacing things common d/t topographic disorientation and visuospatial
- may need assistance with complicated tasks (e.g., operating appliances and managing finances) - Stage 3 (8-12 years): Severe dementia, global aphasia, mutism
- profound cognitive impairments requiring 24-hour assistance
- behavioral abnormalities (e.g., hallucinations and nighttime wandering) - Stage 4: Severe dementia and complete dependence
- disoriented and no longer capable of following basic routines
- hallucinations and incontinence - Stage 5: Severe disability
- noncommunicative and difficulty chewing/swallowing -> muscle wasting
- increased vulnerability to pneumonia and other illnesses
Alzheimer’s disease rule outs
Vascular cognitive impairment (VCI) - more likely to have rapid onset of symptoms, stepwise symptom progression (though this is not always the case), or symptoms occur within 3 months of an identified cerebrovascular event
Lewy body disease (LBD) - mild memory deficits + visuospatial impairment with extrapyramidal symptoms, visual hallucinations, REM sleep behavior disorder, and/or fluctuating symptoms
Frontotemporal disease (FTD) - personality/behavioral changes most prominent early
- behavioral variant - presents with pronounced behavioral disturbances
- language variant - presents with pronounced language and semantic knowledge deficits
Parkinson’s disease
Normal pressure hydrocephalus
Delirium - d/t urinary tract infections, medication effects, metabolic issues
Alzheimer’s disease neuropsychological expectations
Tests of episodic memory (verbal learning/delayed recall), language (confrontation naming/word list generation), and EF (cognitive flexibility) most sensitive to differentiating AD from normal aging
Memory - typically first symptoms (rapid forgetting, intrusion errors during recall, heightened recency recall effects, impaired recognition)
- delayed verbal recall tends to be most sensitive
- anterograde > retrograde memory loss initially, then retrograde loss temporal gradient with older autobiographical memories better persevered
Intelligence - crystalized abilities normal during early stages (sight word reading, vocabulary)
Attention - basic attention (digit span forward) intact in early stages
Language - word finding difficulties, phonemic/semantic paraphasic errors on confrontation naming early. Echolalia and mutism in later stages.
Visuospatial - early: may have deficits in geographical orientation, spatial perception, and design copy (visual attention, scanning, and discrimination intact until middle/late stages)
EF - difficulties with flexibility, reasoning, judgment
Sensorimotor - decline in later stages, including ideomotor apraxia (impaired performance of skilled gesture on verbal command/imitation)
Emotion/Personality - do not become apparent until middle/late stages, including anxiety, suspiciousness, apathy/lack initiation, socially withdrawn
Sundowning
Behavioral changes that can occur in the late afternoon or evening in people with dementia, which can include increased confusion, agitation, aggression, hallucinations, paranoia,
increased disorientation, or pacing/wandering.
Parkinsonian signs of late stages Alzheimer’s disease
rigidity, gait disturbance,
and bradykinesia
Memory functions that are typically impaired in early-stage Alzheimer’s disease
episodic memory
semantic memory
visual memory
procedural memory is not usually affected
Medication considerations for Alzheimer’s disease
acetylcholine inhibitors - may improve initially and decline at a slower pace
tricyclic antidepressants - avoid; they may cause side effects which negatively affect memory
SSRIs - are often the preferred antidepressant for people with AD and depression because they have a lower risk of causing interactions with
other medications.
Alzheimer’s disease has been described as a disease of…
association cortices
Neuronal degeneration has been found to be greatest in the medial temporal lobe and heteromodal association areas,
with sparing of the primary sensory and motor cortices until later in the disease process. Most vulnerable are the cortico-cortical projections, disruption of which can contribute to degradation of the hippocampal formation and subsequent memory impairment.
Early Alzheimer’s disease should be suspected if the family complains of significant changes in the patient’s…
capacity to function in unfamiliar settings
In patients with Alzheimer’s disease, cholinesterase inhibitors given in the early stages of illness may delay…
nursing home placement
What is the apolipoprotein E pattern would be most suggestive of Alzheimer’s disease?
ε3 and ε4
Early-onset dementia is typically associated with:
more rapid decline
Which neuropathological change shows the strongest relationship with cognitive decline in Alzheimer’s disease?
Tau
The average age of onset for Alzheimer’s disease is approximately ?? years old.
75
What neuropathological change correlates best with severity of cognitive impairment in patients with Alzheimer’s dementia?
synaptic loss.
Amyloid plaque occurs primarily before observed cognitive changes. Severity of cognitive decline is associated with synaptic loss, as well as neurofibrillary tangles
ApoE ε4
The ε4 allele of the Apolipoprotein E (APOE) gene is the strongest genetic risk factor for late onset Alzheimer’s disease. Carriers of 1 e4 allele have an increased risk compared to general population, and those with two copies of the e4 allele are at greatest risk
What chromosome appears to be related to the development of amyloid plaques?
Chromosome 21, which is also involved in Down syndrome
Features of multiple system atrophy:
degenerative neurological condition that typically involves autonomic dysfunction (incontinence or orthostatic hypotension) and cerebellar syndrome (e.g., gait ataxia), hence multiple systems
Individuals with latent herpes simplex virus (HSV) infection are at increased risk for ?? later in life:
Alzheimer’s disease
On average, how many causes of DEMENTIA are reversible?
5%
Alzheimer’s vs depression
Cognitive deficits in depression are less severe than AD
Depressed patient are less likely than AD to show impaired naming ability, verbal fluency, and visuospatial ability
Depressed patients exert less effort and may complain more about their cognitive difficulties than AD
What disorder is closely linked to degeneration of (muscarinic) acetylcholine synthesizing neurons in the basal forebrain?
Alzheimer’s (specifically, muscarinic acetylcholine)
Does depression increase or decrease with severity of dementia?
Decreases
Which area of memory is found to be most intact in normal aging?
Remote memory
Most common neurologic manifestation of HIV:
emotional lability and delirium associated with HIV-associated dementia
apolipoprotein E e4 allele (APOE4) is associated with the severity of the severity of which two dementias?
Alzheimer’s
Lewy body
The gene Apolipoprotein E (APOE) is encoded on what chromosome?
19
