What are some properties of AD?
- Most common dementing illness
- 50% of all primary dementing illnesses are AD
- Age biggest risk factor
- 65-70: 2%
- 80: 20%
- Problems of ageing population
Diagnosis of Alzheimer’s Disease?
- Definite AD: Pathology
- Can only diagnose Dementia of the Alzheimer Type (DAT)
- DAT: Typical pattern of symptoms of Alzheimers
When does AD rise? What are some genetic markers of early onset?
Onset
- Majority arise Sporadically
- Age major risk factor
Early onset (Genetic)
- Autosomal dominant:
- Amyloid precursor protein (APP)
- Presinilin 1 (PSEN1)
- Presenilin 2 (PSEN2)
- Alters production of amyloid β (Aβ) peptide
- Principal component of senile plaques
- Alters production of amyloid β (Aβ) peptide
Other than genetic marks, what are some groups of people who are more vulnerable? What are the factors?
- Down syndrome
- Occurs earlier 40s
- No precipitating/cause factors known
- Head injury has some evidence
- Can have sudden decompensation
- Other event (like a stroke) triggers AD
Clinical Features of DAT: Onset and Course?
Onset
- Insidious (1-2 years prior to diagnosis)
Course
- Slow deterioration over years (M = 8.5 years to death)
- Occasional plateaus in deterioration
Clinical Features of DAT: Phases?
Phase 1
- 2-3 years
Phase 2
- Rapid deterioration
Phase 3
- Terminal Stage
Clinical Features of DAT: Phase 1?
- Failing memory
- Amnestic presentation
- Most Common
- MTL
- Muddled inefficiency in daily activites
- Spatial disorientation
- Don’t know how to get home
- Mood disturbance
- Agitated or apathetic
Clinical Features of DAT: Phase 2?
- Intellect and personality deteriorate
- Focal symptoms
- Dysphasia, dyspraxia, agnosia and acalculia, wernicke
- Temporal
- Dysphasia, dyspraxia, agnosia and acalculia, wernicke
- Disturbance of posture and gait, increased muscle tone
- Delusions/hallucinations can occur
Clinical Features of DAT: Phase 3?
- Profound apathy
- Bed ridden
- Eventually lose neurological function
- Bodily wasting occurs
What is Probable AD?
- Deficits in 2 or more areas of cognition
- Amnestic presentation
- Most common
- Nonamnestic presentations
- Language, Visuospatial, Executive dysfunction
- Amnestic presentation
- Progressive worsening of memory/cognitive functions
- No disturbance of consciousness
- Onset between 40 and 90
- Absence of other causes
- Biomarkers
What is Possible AD?
- Made on the basis of dementia syndrome, however…
- Variation in onset, presentation, or clinical course
- Presence of another disorder, not considered causing dementia
What is Definite AD?
Histopathological evidence of AD obtainedfrom biopsy or autopsy
What is the pathology of AD?
- Intensity of these features correlate closely with dementia severity
- Grossly atrophied brain - whole brain shrunken
- Frontal and temporal lobes > parieto-occipital regions
- Note: This a different pattern
- Frontal and temporal lobes > parieto-occipital regions
- Extensive degeneration of neurons
- Gilal cell proliferation
- Extensive senile plaques and neurofibrillary tangles
What is the Course of neuropathological changes? What is the key criteria for getting a dementia diagnosis?
- Commence in MTL
- Spread to Temporal
- Spread to Parietal
- Spread to Frontal
(MTL > Temporal > Parietal > Frontal)
Note: Must see functional impact for dementia diagnosis
Clinical pattern of cognitive impairment in DAT: Amnesia?
Intially what happens, when MTL impairs?
- Anterograde memory:
- Impaired new learning
- Impaired delayed recall
- Impaired recognition memory
- Retrograde memory
- Intact for remote memories
- Reduced for recent retrograde memories
Clinical pattern of cognitive impairment in DAT – Amnesia?
What happens when spread posteriorly to posterior temporal cortex and parietal cortex?
Temporal
- Wernicke-type aphasia (Word salad. Gramatical/Fluent but content-less)
Parietal
- Visuospatial deficits and topographical disorientation
- Dyspraxia, agnosia and acalculia
Clinical pattern of cognitive impairment in DAT – Amnesia. What happens when spread to frontal lobe?
- Executive Dysfunction
- Apathy (most common)
- Agitation
How do we treat AD? What cannot be done in AD?
- Work by trying to re-balance the action of acetylcholine
- This only helps in maintain AD
- Improve quality of life, not length of life
- This only helps in maintain AD
- No treatment to stop disease
- No clear evidence that anything prevents AD (Diet, Exercise, etc)
AD vs Normal Ageing?
- Pathological changes are considerably greater in AD
- Cognitive function in DAT is significantly impaired relative to same-aged peers
Case study of AD: MK. What does she have initially (Not the assessment)?
- Increasingly forgetful in last 2-3 years
- Diabetes and hypertension,
- Depression (anti-depressent had no effect)
- Low average premorbid intellect
Could be: DAT, Depression, or just worried
Case study of AD: MK. Initial Assessment?
Mild Cognitive Impairment. No Progression
Frontal: ok
- Intact frontal lobe function (spread to frontal)
- Attention and speed of information processing
Parietal: ok
- Intact visuospatial skills (No spread to parietal)
- No language deficits (No spread to temporal)
Memory: no
- Memory impairment
- Impaired relational learning (Amnesia type)
- Impaired recall and recognition (No encoding)
Case study of AD: MK. Assessment 2?
DAT. Shows progression and functional impact.
Frontal: ok
- Intact frontal lobe function (spread to frontal)
- Attention and intellect
Parietal: no (Change from intial assessment)
- Subtle visuospatial deficit (spread to parietal)
- Deficit in language (spread to temporal)
- Wenicke-type aphasia
Memory: no
- Memory impairment (Unchanged from initial assessment)
- Impaired relational learning (Amnesia type)
- Impaired recall and recognition (No encoding)
