Major/Mild Neurocog D/O due to Alzheimer's Disease

Question 1

criterion A for M/M NCD due to alzheimers disease

Answer 1

criteria are met for major or mild NCD

Question 2

criterion B for M/M NCD due to alzheimers disease

Answer 2

there is INSIDIOUS onset and GRADUAL progression of impairment in one or more cognitive domains

(for major NCD, two domains must be impaired)

Question 3

criterion C for M/M NCD due to alzheimers disease

Answer 3

criteria are met for either probably or possible alzheimers disease (see next cards)

Question 4

for major NCD, when is probably Alzheimers disease diagnosed

Answer 4

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)

Question 5

for mild NCD, how do you diagnose probable alzheimer’s disease

Answer 5

if there is evidence of a causative alzheimers disease genetic mutation from either genetic testing or family history

Question 6

for mild NCD, how do you diagnose possible alzheimers disease

Answer 6

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

Question 7

what are the core features of M/M NCD due to alzheimers disease, beyond the NCD syndrome

Answer 7

insidious onset

gradual progression of cognitive and behavioural symptoms

Question 8

what is the typical presentation of M/M NCD due to alzheimers disease

Answer 8

amnestic

(i. e with impairment in memory and learning)
* unusual non-amnestic, i.e with visuospatial and logopenic aphasic variants, do exist

Question 9

how does NCD due to alzheimers disease typically manifest in the mild NCD phase

Answer 9

typically with impairment in memory and learning, sometimes accompanied by deficits in executive function

Question 10

how does NCD due to alzheimers disease typically manifest in the major NCD phase

Answer 10

visuospatial/perceptual motor ability and language will also be impaired (particularly when NCD is moderate to severe)

Question 11

what cognitive domain tends to be preserved until late in the course of M/M NCD due to alzheimers disease

Answer 11

social cognition and procedural memory (dancing etc)

Question 12

in specialty clinical settings, what % of individuals with major NCD due to alzheimer’s disease will have behavioural and psychological manifestations

Answer 12

80%

*these behavioural and psychological symptoms are as, or more, distressing than cognitive manifestations are are frequently the reason WHY CARE IS SOUGHT

Question 13

what psychological manifestation is often seen at the mild stage, or the mildest level of major NCD due to alzheimer’s disease

Answer 13

depression and/or apathy

Question 14

what behavioural or psychological manifestations are common with moderately severe major NCD

Answer 14

psychotic features

irritability

agitation

combativeness

wandering

Question 15

what neurological manifestations can be observed late in the illness of NCD due to alzheimers disease

Answer 15

gait disturbance

dysphagia

incontinence

myoclonus

seizures

Question 16

what is the prevalence of overall dementia

Answer 16

in developed countries:

5-10% in 7th decade–> rises to 25% thereafter

Question 17

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?

Answer 17

7% between ages 65-74

53% between ages 75-84

40% after age 85

Question 18

what % of all dementias (major NCDs) are attributable to alzheimers disease

Answer 18

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

Question 19

what is the mean survival after diagnosis of M/M NCD due to alzheimers disease

Answer 19

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

Question 20

what often happens to those in late stage of alzheimer’s disease

Answer 20

they are eventually mute and bedbound

Question 21

what is the most common cause of death in those who survive the full course of M/M NCD due to alzheimers disease

Answer 21

aspiration

Question 22

when is the onset of most symptoms of M/M NCD due to alzheimers disease

Answer 22

either or ninth decade of life

Question 23

how old are those in whom early onset forms of M/M NCD due to alzheimers disease are seen

Answer 23

fifth or sixth decade of life

*these are typically related to known causative mutations

Question 24

does the course of the disease differ between early and late onset variants of M/M NCD due to alzheimers disease

Answer 24

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

Question 25

list risk factors for M/M NCD due to alzheimers disease

Answer 25

1. environmental
   - -TBI raises risk
2. genetic
3. 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

Question 26

what is the strongest risk factor for M/M NCD due to alzheimers disease

Answer 26

age

Question 27

list the genetic mutations associated with M/M NCD due to alzheimers disease

Answer 27

1. polymorphism apolipoprotein E4
   - -increases risk and decreases age of onset, especially in homozygous people
2. there are also extremely rare causative alzheimer’s genes
3. those with trisomy 21 develop alzheimer’s if they survive to midlife

Question 28

what are the neuropathological hallmarks of Alzheimers disease

Answer 28

1. cortical atrophy
2. amyloid-predominant neuritic plaques
3. tau-predominant neurofibrillary tangles
   * may be confirmed via postmortem histopathological examination

Question 29

what are the known causative alzheimers genes (mutations in which cause alzheimers disease)

Answer 29

1. amyloid precursor protein (APP)
2. presenilin 1 (PSEN1)
3. presenilin 2 (PSEN2)
   * may be involved in early onset cases with autosomal dominant inheritance

Question 30

can apolipoprotein E4 serve as a diagnostic marker?

Answer 30

no–it is only a risk factor and neither necessary nor sufficient for disease occurrence

Question 31

which alzheimers causative gene has commerically available testing

Answer 31

PSEN1

Question 32

which neuropathological change occurs early in the disease course of alzheimers? why is this relevant?

Answer 32

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

Question 33

what signs on an MRI may suggest (but cannot confirm) alzheimers

Answer 33

signs of neuronal injury, such as hippocampal and temporoparietal cortical atrophy

Question 34

what signs on a fluorodeoxyglucose PET scan may suggest (but cannot confirm) alzheimers

Answer 34

temporoparietal hypometabolism

Question 35

what signs on CSF analysis may suggest (but cannot confirm) alzheimers

Answer 35

elevated total tau and phospho-tau levels

Question 36

ddx for M/M NCD due to alzheimers disease

Answer 36

1. other neurocognitive disorders
2. other concurrent, active neurological or systemic illness
3. MDD

Question 37

which other NCD may share many features with M/M NCD due to alzheimers disease

Answer 37

vascular NCD–> usually vascular has a history of stepwise decline, associated temporally with CVAs etc, but when there isnt, it can shrae many features