AD diagnosis and markers Flashcards
(9 cards)
Criteria for AD diagnosis
- Insidious onset; symptoms develop gradually over months - years
- Cognition is worsening, from report or observation
- Cognitive impairment in one of two categories
1. Amnestic presentation: Most common, main impairment is in memory
- Nonamnestic or atypical presentation: Main impairment is in language (word finding difficulties) or EF or visuospatial function
- For both categories; there should be disorders in other cognitive functions as well.
In DSM 5
Major neurocognitive disorder
- Significant cognitive decline from previous level of performance based on
report patient or informant AND clear objective deficits (>2 SD below appropriate norm population) - Cognitive deficits sufficient to interfere with independence
- Cognitive deficits do not exclusively occur in context of delirium
- Cognitive deficits can not be attributed to Axis 1 disorder (e.g. depressionor schizophrenia)
Differentials
Other degenerative disorders
- Eg Parkinson’s, Lewy Body disease
Medical/psych conditions
- Eg. tumor, depression
Reversible conditions
Eg encephalitis (brain inflammation, fast onset), B12 deficiency
Uncertainty of diagnosis
Definite diagnosis is only possible post-mortem
- plaques and tangles can only be confirmed microscopically, when alive they use biomarkers to assess
Only proven post mortem if:
- the person met clinical and cognitive criteria of probable AD during life
- there’s AD pathology present in the brain
Ante mortem diagnosis:
- Probable AD; meets criteria for AD, no evidence of alternative reason for symptoms
- possible AD: progressive decline uncertain, negative biomarkers and mixed presentation.
Biomarkers
Can help with the certainty of diagnosis.
Negative biomarkers are an indicator of AD
- Low CSF Abeta; low levels of amyloid beta in the cerebrospinal fluid
- Elevated tau in CSF
- Amyloid beta imaging in PET (red/yellow = high concentration of amyloid
- Decreased fluorodeoxy-glucose (DFG) uptake on PET; less neuronal activity so less brain matabolism
- Disproportionate brain atrophy in temporal lobe (in particular hippocampus)
Risk factors
Age (0.5-1% of 60-64 yr olds, 10-30% of 85+)
Family history
- Causative genes
- Susceptible genes
Sex (women to men is 2:1, cognitive impairments also more severe in women)
Health; TBI, obesity, smoking, diabetes, chronic stress, alcohol, inactivity etc
Causal Genes
3 known: mutations of amyloid precurser protein gene, Presenilin 1 and 2 gene
Person w the mutation will develop AD if they live until middle or old age.
Account for 5% of AD cases
All mutations are associated with early onset dementia
Susceptibility genes
Genetic mutations that increase the risk of AD.
*Not all people with AD carry the gene
Best known: APOE gene. has different forms (E2, E3, E4).
- E2 reduces risk for AD
- E4 increases risk for late onset AD
Reasons for sex difference
Genetic;
- APOE4 allele; women have 4x higher risk
Hormones;
- Changes in oestrogen levels
- hormonal replacement therapy is mid life can reduce risk BUT after menopause it can increase the risk
Reserve;
Women were not allowed to do shit so they may have lower reserve
