Dementia

Seite 1

Alzheimer’s

Clinical features:

Cognitive difficulties

Apathy

Impairment of learning and memory

Wandering

Irritability

Delusions

Neuropathology:

Amyloid plaques – cleavage of normal APP protein, leads to

formation of plaques

Cortical atrophy

Neurofibrillary tangles

Genetics:

Early onset form is typically familial, inherited in an autosomal dominant manner (late onset

is multifactorial)

Genes involved: APP, PS1, PS2

Alzheimer’s brains stain to show accumulation of mutant tau

protein

Clinical Features:

Behavioural and personality changes

Loss of insight, loss of inhibition, loss of taste

Executive function deficits

Language compromised

Loss of short-term memory

Physical symptoms similar to Parkinson’s or Motor Neuron

Disease - some people have MND as well

Two subtypes: behavioural subtype (early disinhibition,

socially inappropriate, impulsive etc) and primary progressive aphasia (starts

with loss of language ability)

Genetics:

Can be caused by various genes can be familial (most) or

sporadic (few)

If inherited, typically in an autosomal dominant manner

CADASIL

Hereditary stroke disorder

Caused by mutation in the NOTCH3 gene

Autosomal dominant inheritance

Clinical features:

Migraines and transient ischemic attacks (typical age of

onset 40-50)

MRI can detect changes before symptoms

Associated w/ dementia

Seizures, depression, manic episodes

Motor disability – pseudobulbar palsy (inability to control

facial movements), tetraplegia (partial or total loss of control of limbs and

torso)

MRI findings:

Myelin loss

Penetrating white matter

Anterior temporal lobes most severely affected region

Clinical features:

Motor – tremor, slowness of movement, rigidity

Neuropsychiatric – executive dysfunction, high risk of

dementia (6x), depression, anxiety, apathy, delusions

Inheritance:

Familial form can be dominant or recessive inheritance

Accounts for 4% of dementia

15% cases are familial, rest are sporadic

Early onset (

PARK1 mutation in autosomal dominant families

PARK2 mutation in autosomal recessive families (often

consanguineous)

PARK8 – most common autosomal dominant gene

PARK6 – autosomal recessive

Alzheimer's

frontotemporal dementia

CADASIL

parkinson's