Major/Mild Neurocog D/O due to Alzheimer's Disease Flashcards
criterion A for M/M NCD due to alzheimers disease
criteria are met for major or mild NCD
criterion B for M/M NCD due to alzheimers disease
there is INSIDIOUS onset and GRADUAL progression of impairment in one or more cognitive domains
(for major NCD, two domains must be impaired)
criterion C for M/M NCD due to alzheimers disease
criteria are met for either probably or possible alzheimers disease (see next cards)
for major NCD, when is probably Alzheimers disease diagnosed
if EITHER the following is present:
C–> evidence of a causative Alzheimer’s genetic MUTATION from family history or genetic testing
D–> all THREE of the following are present:
a) clear evidence of decline in MEMORY AND LEARNING and at least one other cognitive domain (based on detailed history or serial neuropsychological testing)
b) STEADILY progressive, gradual decline in cognition, without extended plateaus
c) NO evidence of mixed etiology (i.e absence of other neurodegenerative or cerebrovascular disease, or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline)
* otherwise, only POSSIBLE alzheimer’s disease should be diagnosed (if neither of the above is present)
for mild NCD, how do you diagnose probable alzheimer’s disease
if there is evidence of a causative alzheimers disease genetic mutation from either genetic testing or family history
for mild NCD, how do you diagnose possible alzheimers disease
if there is NO evidence of a causative alzheimer’s disease genetic mutation and all THREE of the following are present:
a) clear evidence of a decline in MEMORY and LEARNING
b) STEADILY progressive, gradual decline in cognition, without extended plateaus
c) no evidence of mixed etiology
d) not better explained by cerebrovascular disease, another neurodegenerative disease or another neurological or systemic disease
what are the core features of M/M NCD due to alzheimers disease, beyond the NCD syndrome
insidious onset
gradual progression of cognitive and behavioural symptoms
what is the typical presentation of M/M NCD due to alzheimers disease
amnestic
(i. e with impairment in memory and learning)
* unusual non-amnestic, i.e with visuospatial and logopenic aphasic variants, do exist
how does NCD due to alzheimers disease typically manifest in the mild NCD phase
typically with impairment in memory and learning, sometimes accompanied by deficits in executive function
how does NCD due to alzheimers disease typically manifest in the major NCD phase
visuospatial/perceptual motor ability and language will also be impaired (particularly when NCD is moderate to severe)
what cognitive domain tends to be preserved until late in the course of M/M NCD due to alzheimers disease
social cognition and procedural memory (dancing etc)
in specialty clinical settings, what % of individuals with major NCD due to alzheimer’s disease will have behavioural and psychological manifestations
80%
*these behavioural and psychological symptoms are as, or more, distressing than cognitive manifestations are are frequently the reason WHY CARE IS SOUGHT
what psychological manifestation is often seen at the mild stage, or the mildest level of major NCD due to alzheimer’s disease
depression and/or apathy
what behavioural or psychological manifestations are common with moderately severe major NCD
psychotic features
irritability
agitation
combativeness
wandering
what neurological manifestations can be observed late in the illness of NCD due to alzheimers disease
gait disturbance
dysphagia
incontinence
myoclonus
seizures
what is the prevalence of overall dementia
in developed countries:
5-10% in 7th decade–> rises to 25% thereafter
according to US census data, what % of those diagnosed with alzheimer’s disease are between:
ages 65-74?
ages 75-84?
ages 85 or older?
7% between ages 65-74
53% between ages 75-84
40% after age 85
what % of all dementias (major NCDs) are attributable to alzheimers disease
60% to over 90% depending on setting and diagnostic criteria
*mild NCD due to alzheimers is likely to represent a substantial fraction of MCI as well
what is the mean survival after diagnosis of M/M NCD due to alzheimers disease
10 years
*this reflects the advanced age of those diagnosed rather than the course of the disease–> some people can live as long as 20 years post diagnosis
what often happens to those in late stage of alzheimer’s disease
they are eventually mute and bedbound
what is the most common cause of death in those who survive the full course of M/M NCD due to alzheimers disease
aspiration
when is the onset of most symptoms of M/M NCD due to alzheimers disease
either or ninth decade of life
how old are those in whom early onset forms of M/M NCD due to alzheimers disease are seen
fifth or sixth decade of life
*these are typically related to known causative mutations
does the course of the disease differ between early and late onset variants of M/M NCD due to alzheimers disease
no–> symptoms and pathology do not differ markedly
BUT–> those diagnosed with early onset variants are more likely to survive the full course of the disease whereas older people generally have other comorbidities
list risk factors for M/M NCD due to alzheimers disease
- environmental
- -TBI raises risk - genetic
- physiological
- -multiple vascular risk factors influence risk for alzheimers and may act by increasingn cerebrovascular pathology or also through direct effects on alzheimer’s pathology
what is the strongest risk factor for M/M NCD due to alzheimers disease
age
list the genetic mutations associated with M/M NCD due to alzheimers disease
- polymorphism apolipoprotein E4
- -increases risk and decreases age of onset, especially in homozygous people - there are also extremely rare causative alzheimer’s genes
- those with trisomy 21 develop alzheimer’s if they survive to midlife
what are the neuropathological hallmarks of Alzheimers disease
- cortical atrophy
- amyloid-predominant neuritic plaques
- tau-predominant neurofibrillary tangles
* may be confirmed via postmortem histopathological examination
what are the known causative alzheimers genes (mutations in which cause alzheimers disease)
- amyloid precursor protein (APP)
- presenilin 1 (PSEN1)
- presenilin 2 (PSEN2)
* may be involved in early onset cases with autosomal dominant inheritance
can apolipoprotein E4 serve as a diagnostic marker?
no–it is only a risk factor and neither necessary nor sufficient for disease occurrence
which alzheimers causative gene has commerically available testing
PSEN1
which neuropathological change occurs early in the disease course of alzheimers? why is this relevant?
amyloid beta-42 deposition in the brain occurs early
we care because amyloid based tests such as amyloid imaging on brain PET scans and reduced levels of amyloid beta-42 in the CSF may have diagnostic value
what signs on an MRI may suggest (but cannot confirm) alzheimers
signs of neuronal injury, such as hippocampal and temporoparietal cortical atrophy
what signs on a fluorodeoxyglucose PET scan may suggest (but cannot confirm) alzheimers
temporoparietal hypometabolism
what signs on CSF analysis may suggest (but cannot confirm) alzheimers
elevated total tau and phospho-tau levels
ddx for M/M NCD due to alzheimers disease
- other neurocognitive disorders
- other concurrent, active neurological or systemic illness
- MDD
which other NCD may share many features with M/M NCD due to alzheimers disease
vascular NCD–> usually vascular has a history of stepwise decline, associated temporally with CVAs etc, but when there isnt, it can shrae many features
