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dementias Flashcards

1
Q

what are the variants of FTD

A

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

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2
Q

what are the subtypes of dementia?

A

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%)

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3
Q

what are the four proteins implicated in dementia

A

TDP43,
Tau,
Alphasynuclein,
Amyloid

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4
Q

what is the protein pathology of BvFTD

A

50% Tau, 50% TDP43

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5
Q

what are the four subtypes of BvFTD

A

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

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6
Q

what pattern does FUS pathology have?

A

frontal paralimbic atrophy and severe caudate nucleus involvement

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7
Q

what are GRN mutations associated with?

A

asymmetrical frontal, temporal and inferior parietal lobe atrophy

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8
Q

MAPT mutations are associared with what?

A

symmetrical anteromedial temporal lobe and orbitofrontal grey matter atrophy

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9
Q

Microtubule associated protein tau (MAPT) can lead to what?

A

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

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10
Q

progranulin mutations can lead to what?

A

tau negative, ubiquitin, and TDP-43 positive inclusions,

episodic memory deficits (10%-30%)

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11
Q

describe the link between C9orf72 and dementia

A

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.

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12
Q

what does subcortical dementias include?

A

vascular dementia,
DLB,
parkinsons with dementia

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13
Q

what are the symptoms of subcortical dementias

A

slowing, attention and executive function.

Characteristic cognitive features:

set shifting difficulties in PD,

marked slowing in PSP,

Executive difficulties and impaired retrieval in HD

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14
Q

what percentage of MS patients have cognitive dysfunction

A

54 to 65

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15
Q

describe frontotemporal dementia

A

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

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16
Q

what is MCI

A

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

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17
Q

what is the prevalence of depression in MCI and dementia compared to old age?

A

old age: 10-20%

dementia: 9-68% (incidence increases with severity)

MCI: 26-63%

18
Q

what gene is a major risk factor for dementia depression?

A

ApoE-4

19
Q

how do the treatments for depression and dementia overlap?

A

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

20
Q

what are the pharmacological reccomendations for treatment of AD NICE 2011

A

Acetylcholinesterase inhibitors mild-moderate AD:

donepazil, galantamine, rivastigmine.

memantine:

moderate AD who are intolerant to or contraindication to acetylcholinesterase inhibitors

or severe AD

21
Q

what three principles should be followed for pharmacological treatment of AD (NICE 2011)

A

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

22
Q

ICD-10 Depressive disorder

A

depressive symptoms:

depressed mood, anhedonia, reduced energy

two of which should be present for over two weeks

23
Q

what are the difficulties that arise in diagnosing depression in dementia?

A

similar cognitive problems seen in depression (memory, concentration, apathy, exec function, physical complaints)

other causes:

thyroid, weight loss
loneliness, isolation
bereavement

24
Q

what are the features of depression in the elderly?

A 
sadness
fatigue
loss of interest in hobbies
withdrawal
weight loss
sleep disturbances
fixation on death
25
Q

what is vascular cognitive impairment?

A

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

26
Q

what are the leading causes of vascular cognitive impairment?

A

Large artery-multi-infarct dementia

small vessel disease

strategic infarcts

intracranial haemorhage

intracranial vascular malformations

cerebral amyloid angiopathy

CADASIL

cerebral vasculitis

Mitochondrial disease

MoyaMoya

27
Q

definition of vascular dementia?

A

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

28
Q

describe the epidemiology of vascular dementia

A

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

29
Q

describe the differences between VD and AD

A

onset may be abrupt

episodic memory more severely affected in AD

whereas attention/executive function, semantic memroy and visuospacial skills more impaired in VaD

30
Q

name three bedside cognitive assessments for VaD and AD

A

MoCA: montreal cognitive assessment

ACE-R:Addenbrooke’s cognitive examination

MMSE: mini mental state examination

31
Q

what changes occur in MRI for small vessel disease

A

high signal intensity

referred to as:

white matter hyperintensities

32
Q

what four types of infarcts are associated with small vessel disease?

A

med cerebral artery
post cerebral artery
watershed infarcts
lacunar infarcts

33
Q

what did the PROGRESS trials show?

what did Syst-Eur show?

A

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

34
Q

what are strategic infarcts?

A

bilateral thalamic infarcts secondary to AF and embolic stroke

35
Q

what degenerative condition can cause vascular dementia?

A

amyloidosis

deposition of Amyloid beta

vessels friable and bleed or haemmorhage

36
Q

how can vasculitis lead to vascular dementia

A

damaged inflamed blood vessels-local thrombosis and ischaemia

37
Q

how is vascular dementia managed?

A

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

38
Q

PODCAST TRIAL

A

a trial currently being run:

prevention of decline in cognition after stroke trial

intensive versus guideline blood pressure lowering

MMSE, ACE assessments

39
Q

what imaging is useful for vascular dementia?

A

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

40
Q

where could treatment of VaD go in the future?

A

agressive population management of hypertension

screening of stroke patients

early drug treatment of MCI

neurodegeneration (15 decks)

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