dementias Flashcards
what are the variants of FTD
behavioral variant (BvFTD-50%),
language varients (semantic dementia, primary non fluent aphasia, logophenic aphasia)
FTD-MND,
Movement disorder plus dementis (Cortico basal syndrome, progressive supranuclear palsy (PSP)
PDD & DLB
what are the subtypes of dementia?
Alzheimer’s disease (62%),
Vascular dementia (17%),
mixed dementia (AD & VaD) 10%,
Dementia with Lewy bodies (DLB-4%),
Frontotemporal Dementias (2%)
parkinsons dementia (2%)
others (3%)
what are the four proteins implicated in dementia
TDP43,
Tau,
Alphasynuclein,
Amyloid
what is the protein pathology of BvFTD
50% Tau, 50% TDP43
what are the four subtypes of BvFTD
1) temporal dominant subtype associated with MAPT mutations,
2) temporofrontoparietal subtype associaed with GRN mutations but also corticobasal degeneration,
3) frontal dominant, 4) frontotemporal subtypes
what pattern does FUS pathology have?
frontal paralimbic atrophy and severe caudate nucleus involvement
what are GRN mutations associated with?
asymmetrical frontal, temporal and inferior parietal lobe atrophy
MAPT mutations are associared with what?
symmetrical anteromedial temporal lobe and orbitofrontal grey matter atrophy
Microtubule associated protein tau (MAPT) can lead to what?
dementia-dominant phenotype with behavioral changes such as dis-inhibition and obsessive compulsive behavior,
a parkinsonism-dominant phenotype with CBS or PSP like syndromes.
Patients may develop language problems eg mild semantic impairment
progranulin mutations can lead to what?
tau negative, ubiquitin, and TDP-43 positive inclusions,
episodic memory deficits (10%-30%)
describe the link between C9orf72 and dementia
cooper-knock et al 2012: dementia was present in 35% of patients or close family members with C9ORF72 mutation
based on diagnosis established retrospectively with clinical case notes.
what does subcortical dementias include?
vascular dementia,
DLB,
parkinsons with dementia
what are the symptoms of subcortical dementias
slowing, attention and executive function.
Characteristic cognitive features:
set shifting difficulties in PD,
marked slowing in PSP,
Executive difficulties and impaired retrieval in HD
what percentage of MS patients have cognitive dysfunction
54 to 65
describe frontotemporal dementia
personality and behavior change followed by breakdown in attention and executive function
characteristic features:
Progressive Non-fluent Aphasia: reduced fluency, agrammatical speech, impaired repetition, intact comprehension,
sparing of memory and visuo-spatial functions
Semantic dementia/progressive fluent aphasia:
anomia,
impaired comprehension, sparing of episodic memory,
visual problem, solving and visuo-spacial function
what is MCI
a syndrome defined as:
cognitive decline greater than expected for an individual’s age and education but does not interfere notable with activities of daily life
amnesic type: 10-15% convert to AD
what is the prevalence of depression in MCI and dementia compared to old age?
old age: 10-20%
dementia: 9-68% (incidence increases with severity)
MCI: 26-63%
what gene is a major risk factor for dementia depression?
ApoE-4
how do the treatments for depression and dementia overlap?
treating depression often improves short term memory
augmentation of cholinesterase inhibitors with SSRI may improve ADLs and global functioning in patients with AD
Donepezil delays progression to AD in MCI subjects with depressive symptoms
what are the pharmacological reccomendations for treatment of AD NICE 2011
Acetylcholinesterase inhibitors mild-moderate AD:
donepazil, galantamine, rivastigmine.
memantine:
moderate AD who are intolerant to or contraindication to acetylcholinesterase inhibitors
or severe AD
what three principles should be followed for pharmacological treatment of AD (NICE 2011)
diagnosis and treatment by a dementia specialist
continued only when haveing a worthwile effect on: cognitive, global, functional or behavioural symptoms
review every 6 months
ICD-10 Depressive disorder
depressive symptoms:
depressed mood, anhedonia, reduced energy
two of which should be present for over two weeks
what are the difficulties that arise in diagnosing depression in dementia?
similar cognitive problems seen in depression (memory, concentration, apathy, exec function, physical complaints)
other causes:
thyroid, weight loss
loneliness, isolation
bereavement
what are the features of depression in the elderly?
sadness fatigue loss of interest in hobbies withdrawal weight loss sleep disturbances fixation on death
what is vascular cognitive impairment?
impairments of memory, language, praxis and spatial orientation secondary to vascular brain pathology
covers:
cognitive impairment no dementia (CIND)
vascular dementia (VaD)
mixed alzheimer’s disease with a vascular component
what are the leading causes of vascular cognitive impairment?
Large artery-multi-infarct dementia
small vessel disease
strategic infarcts
intracranial haemorhage
intracranial vascular malformations
cerebral amyloid angiopathy
CADASIL
cerebral vasculitis
Mitochondrial disease
MoyaMoya
definition of vascular dementia?
DSM-IV: cognitive deficit in more than 2 domains,
focal neurological symptoms and/or signs
impaired social functioning
good sensitivity but low specificity
NINDS-AIREN: research criteria- uses CT/MRI and differentiates possible and probably VD
describe the epidemiology of vascular dementia
2nd most common dementia
1-2% over 70
further 1-2% mixed AD and VD
commoner in men
commoner in SE asian and carribean
25% post stroke after 1 year
incidence of dementia 9 times higher in those who have had a stroke
describe the differences between VD and AD
onset may be abrupt
episodic memory more severely affected in AD
whereas attention/executive function, semantic memroy and visuospacial skills more impaired in VaD
name three bedside cognitive assessments for VaD and AD
MoCA: montreal cognitive assessment
ACE-R:Addenbrooke’s cognitive examination
MMSE: mini mental state examination
what changes occur in MRI for small vessel disease
high signal intensity
referred to as:
white matter hyperintensities
what four types of infarcts are associated with small vessel disease?
med cerebral artery
post cerebral artery
watershed infarcts
lacunar infarcts
what did the PROGRESS trials show?
what did Syst-Eur show?
perindopril + indapamide OD 43% reduction in incidence of stroke and reduced incidence of cognitive decline in those who had a stroke
50% risk reduction incident dementia
what are strategic infarcts?
bilateral thalamic infarcts secondary to AF and embolic stroke
what degenerative condition can cause vascular dementia?
amyloidosis
deposition of Amyloid beta
vessels friable and bleed or haemmorhage
how can vasculitis lead to vascular dementia
damaged inflamed blood vessels-local thrombosis and ischaemia
how is vascular dementia managed?
general dementia management:
referral to community services, legal, ethical provisions (eg driving, competency)
secondary vascular prevention: antiplatelets, statins, antihypertensives
cognitive enhancers: galantamine licensed for mixed VD and AD
PODCAST TRIAL
a trial currently being run:
prevention of decline in cognition after stroke trial
intensive versus guideline blood pressure lowering
MMSE, ACE assessments
what imaging is useful for vascular dementia?
diffusion tensor imaging (DTI) - abnormalities in white matter structure and provides models of brain connectivity
arterial spin labeling (ASL) evaluate cerebral blood flow
measures of global cerebral atrophy and White matter volume changes
where could treatment of VaD go in the future?
agressive population management of hypertension
screening of stroke patients
early drug treatment of MCI
