Flashcards in Alzheimer’s: Clinical Features, Aetiology and Drug Treatment Deck (45)
Clinical features of typical AD?
- Impaired episodic memory (recent memories, but older memories spared)
- head turning sign (look to family for reassurance/confirmation)
- difficulty following convos
- word-finding issues
Anatomical location of dysfunction in impaired episodic memory?
- medial temporal lobe
Clinical features of AD as it progresses?
- increasingly impaired executive function
- increasingly impaired attention
- eventual apraxia
Anatomical location of dysfunction in impaired attention in AD
Frontal and parietal atrophy
Clinical features of atypical AD?
(may not have episodic memory issues at presentation, but will get later)
- visuospatial issues (posterior cortical atrophy)
- primary progressive aphasia (asym. left atrophy)
Age of onset in atypical AD?
Younger age of onset
Cognitive issue that impairs function AND affects 2 cognitive domains (1 of which is memory)]- DSM-IV
[NB: dementia is a syndrome- no assumptions on cause]
Most common neurodegenerative dementia?
Criteria for DLB?
Cognitive impairment before/within 1 year of PD symptoms
(2nd most common dementia)
Define Vascular Dementia?
Dementia w/ step-wise deterioration due to multiple small infarcts (cerebrovascular disease)
Features of Fronto-Temporal Lobar Degeneration (FTLD)?
- behavioural changes
- semantic dementia
- progressive non-fluent aphasia
Investigations for AD?
- MMSE/MMSA (Mini Mental State Examination)
- Montreal Cognitive Assessment (MoCA)
- Addenbrookes Cognitive Assessment (ACE)
Purpose of neuropsychological assessment?
- tests multiple cognitive domains
- excludes DDx (e.g. depression)
- establishes baseline
Structural imaging for AD examples?
- Longitudinal imaging studies
What is seen on MRI of AD?
- General atrophy
- hippocampal atrophy
Why do an MRI for AD?
Functional imaging for AD examples?
- Amyloid PET
- FDG PET
- Tau PET
[NB: no validated Tau ligand, would be useful since tau correlates w/ clinical pathology]
AD on CSF analysis results?
Decreased Aβ, increased tau
How to definitively diagnose AD?
Brain biopsy or post-mortem
Overview of microscopic neuropathology of AD?
- intracellular neurofibrillary tangles (tau)
- neuronal loss
Overview of aetiology of AD?
- oxidative stress
- mitochondrial dysfunction
- interaction w/ vascular damage
- amyloid/tau pathology
Describe the amyloid hypothesis
Increased Aβ accumulation -> tau hyperphosphorylation -> neurofibrillary tangle (NFT)
[NB: tau correlates well w/ cognitive deficits in AD]
1st degree relatives have more than 2x lifetime risk of AD
Risk factors of AD?
- Down’s Syndrome
- vascular risk (DM, HTN)
- female >M (2:1)
- trauma (TBI-> inflammation and increased Aβ)
- CTE (dementia pugilistica)
Genetic causes of AD?
- Familial AD (APP, presenilin 1/2)
- APOE (E4- 5x risk homozygote, E2 protective)
- trisomy 21 (100% have AD by 40yrs)
Protective risk factors for AD?
- education (cognitive reserve effect, neuropathology occurs but onset of AD takes longer)
Relationship between AD pathology and AD symptoms?
Pathology starts 10-20 yrs prior to symptoms/diagnosis
Overview of stages of AD development?
Asymptomatic (increased Aβ) -> MCI (even greater Aβ, increased Tau, decreased memory) -> Dementia (A LOT of Aβ, even greater tau, even greater decrease in memory)
What is Mild Cognitive Impairment (MCI)?
Memory/cognitive issues but no functional impairment (not dementia)
Relationship between amnestic and AD?
Amnestic type have increased likelihood of progression to AD