Dementia

Alzheimer’sClinical 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 geneAutosomal 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