PSYC20006 Lecture Notes - Lecture 12: Amyloid Precursor Protein, Senile Plaques, Acalculia
12 Jun 2018
School
Department
Course
Professor
Lecture 12 - Thursday 6 April 2017
PSYC20006 - BIOLOGICAL PSYCHOLOGY
LECTURE 12
DISORDERS OF MEMORY - ALZHEIMER’S DISEASE
WHAT IS ALZHEIMER’S DISEASE?
•Alzheimer (1907, 1911)
•Commonest of primary dementing illnesses
•Autopsy studies report that approx. 50% of all dementias are AD
•Disease process operates directly on neuronal tissue, rather than damage somewhere else that
impacts neuronal function (Eg. Damage to endocrine system)
•Problem of ageing population
•~ 2% (65-70)
•~ 20% (>80)
•Eventually become dependent and enter supported accommodation
•After WW2 there was a population explosion in the Western World. This group is now the Baby
Boomers. They are now eligible for dementing illnesses.
DIAGNOSIS OF ALZHEIMER’S DISEASE
•Definitive diagnosis of AD can only be made on pathology (autopsy)
•In life – can only diagnose Dementia of the Alzheimer Type (DAT)
AETIOLOGY OF ALZHEIMER’S DISEASE
•Majority arise sporadically
•ApoE (late onset AD). Doesn’t guarantee you will get it; just increases risk of so.
•Rare early onset autosomal dominant cases:
•Mutations in 3 genes: amyloid precursor protein (APP), presinilin 1 (PSEN1), presenilin 2
(PSEN2)
•All alter production of amyloid β (Aβ) peptide – principal component of senile plaques
•Individuals with Down’s syndrome are unusually prone to developing AD
•Typically occurs much earlier (~ 40’s)
•No precipitating factors known
•Can have sudden decompensation
CLINICAL FEATURES
•What does it look like
•Onset is insidious
•1-2 years prior to diagnosis
•Course: slow deterioration
•Years
•Occasionally see plateaus in deterioration
•Death: M = 8.5 yrs after onset (range: 2-20 yrs)
PHASES OF DISEASE PROGRESS
•3 main phases in disease progress
PHASE ONE
•Lasts 2-3 years
•Failing memory (amnestic presentation)
•Muddled inefficiency in Activities of Daily Living (ADL)s
•Spatial disorientation
•Mood disturbance can occur (agitated or apathetic)
Lecture 12 - Thursday 6 April 2017
PSYC20006 - BIOLOGICAL PSYCHOLOGY
PHASE TWO
•More rapid progress of deterioration
•Intellect and personality deteriorate
•Focal symptoms appear (dysphasia, dyspraxia, agnosia and acalculia)
•Agnosia is like the guy in the man who mistook his wife for a hat.
•Acalculia is loss of understanding of numbers and arithmetical processes basically.
•Disturbance of posture and gait, increased muscle tone
•Delusions/hallucinations can occur
PHASE THREE
•Terminal stage
•Profound apathy, become bed ridden
•High level round the clock care needed.
•Eventually lose neurological function. Bodily wasting occurs
MCKHANN et al. CRITERIA
•Working party developed operational criteria for making diagnosis of AD
•Probable AD
•Possible AD
•Definite AD
PROBABLE AD
•Probable AD requires deficits in 2 or more areas of cognition
•Amnestic presentation: most common
•Non amnestic presentations: Language, Visuospatial, Executive dysfunction
•Language is very common dysfunction to have.
•Progressive worsening of memory and/or other cog. Functions.
•Deterioration is occurring over time.
•No disturbance of consciousness
•Onset between 40 and 90
•In the absence of other causes
•Biomarkers; blood tests etc. Presence of biomarkers increase likelihood of AD, but absence of
relevant biomarkers doesn’t mean it’s not AD.
POSSIBLE AD
•Possible AD is the same dementia syndrome but with variations. Different symptoms or onset or
time of onset etc.
•Made on the basis of dementia syndrome if have variations in onset, presentation or clinical
course
•Can be made in the presence of another disorder, which is not considered to be the cause of the
dementia
DEFINITE AD
•Definite AD is histopathological evidence of AD obtained from biopsy or autopsy.
PATHOLOGY OF ALZHEIMER’S DISEASE
•Grossly atrophied brain
•Affects frontal and temporal lobes > parieto- occipital regions
•Extensive degeneration of neurons
•Hippocampi and amygdala. Amnesial-temporal structures
•Accompanying glial cell proliferation
•Extensive amounts of senile plaques
Document Summary
What is alzheimer"s disease: alzheimer (1907, 1911, commonest of primary dementing illnesses, autopsy studies report that approx. 50% of all dementias are ad: disease process operates directly on neuronal tissue, rather than damage somewhere else that impacts neuronal function (eg. Damage to endocrine system: problem of ageing population, ~ 2% (65-70, ~ 20% (>80, eventually become dependent and enter supported accommodation, after ww2 there was a population explosion in the western world. Diagnosis of alzheimer"s disease: definitive diagnosis of ad can only be made on pathology (autopsy, in life can only diagnose dementia of the alzheimer type (dat) Aetiology of alzheimer"s disease: majority arise sporadically, apoe (late onset ad). Clinical features: what does it look like, onset is insidious, 1-2 years prior to diagnosis, course: slow deterioration, years, occasionally see plateaus in deterioration, death: m = 8. 5 yrs after onset (range: 2-20 yrs) Phases of disease progress: 3 main phases in disease progress.
