neurodegeneration and dementia

Question 1

features shared by NDD

Answer 1

progressive - once disease process has begun it continues relentlessly
fatal outcome
associtaed with aging
degeneration of neurones - dysfunction and cell death

Question 2

many of these diseases are caused by

Answer 2

abnormal accumulation of proteins in the CNS

mostly unknown causes - genetic and environmental factors

Question 3

common pathological factors

Answer 3

cmmonest in old age
each disease affects specific neuronal groups
clinical features relate to the anatomy and function of the affected areas
atrophy of affected areas with disease progression - seen on imaging or macroscopically at PM
regional pattern of atrophy may be pathognomonic in some cases

Question 4

microscope appearance of NDD

Answer 4

histopathology shows neuronal loss with variable gliosis
microscopy may show distinctiive cellular inclusions containing specific proteins in either neurones of glial cells eg. NFT, lewy bodies

Question 5

cortical degenerations

Answer 5

alzhiemer disease
frontotemporal lobar degeneration
dementia with lewy bodies

Question 6

akinetic movement disorders

Answer 6

parkinsons disease
progressive supranuclear palsy
corticobasal degeneration
multiple ssystem atrophy (striatonigral degeneration)

Question 7

hyperkinetic syndroms

Answer 7

huntington disease

choreoarthritis

Question 8

cerebellar ataxis

Answer 8

inherited and sporadic

Question 9

diseases of motor systems

Answer 9

motor neurone disease

hereditary spastic paraperesis

Question 10

autonomic disorders

Answer 10

parkinosns disease

multiple system atrophy (shy-drager syndrome)

Question 11

hippocapmus diseases

Answer 11

congnitive changes, memory, behaviour, language

Question 12

basal ganglia diseases

Answer 12

movement disorders
hypokinetic
hyperkinetic

Question 13

cerebellum diseases

Answer 13

ataxia - psinocerebellar ataxia

Question 14

motor system diseases

Answer 14

weakness, difficulty swallowing, respiration, amyotropic lateral sclerosis

Question 15

protein accumulation

Answer 15

Ab amyloid - alzhiemers
Tau - pick disease (3 repeat) or others with 4 repeats
alpha-synuclein
TDP-43
polyglutamine repeat expansions - huntington disease
SOD1, TDP-43
prions

Question 16

dementia

Answer 16

an acquired progressive global impairment of intellect, memory and personality, without impairment of consciousness

Question 17

the definition of dementia excludes

Answer 17

acute confusional state
impairment of consciousness
delirium or depression
mental impairment due to maldevelopment of the brain or due to a brain insult during development

Question 18

main causes of demntia

Answer 18

alziemerhs
dementia with lewy bodies
frontotemporal lobar degeneration
vescular pathology

Question 19

alzheimers disease

Answer 19

progressive and inevitably fatal within 5-15 years
immidiate cause of death often terminal infection eg. pneumonia
3rd most common death in developed world (after vascular disease and cancer)

Question 20

ealry onset alzheimers

Answer 20

<65 yo

Question 21

gold standard for alzeimhers diagnossis

Answer 21

post mortem pathology

Question 22

changes in the brain

Answer 22

reduction in size and atrophy
ventricle increases in size due to decrease volume of white matter
sulci appear expanded and gyri are narrowed
reduced cerebral weight
atrophy of medial temporal lobe

Question 23

histopathological features of alzheimers

Answer 23

amyloid b-protein accumulation - cortical neuritic plaques and cerebral amyloid angiopathy
tau accumulation - neurofibrillary tangles, plaque - associated dystrophic neurites and neuropil threads

Question 24

the amyloid hypothesis

Answer 24

abnormal accumulation of amyloid b protein through to play a key role in initiating and perpetuating the neurotoxic events that culminate in dementia (by reduced clearance rather than increased production
released into the ECS where it aggregates to form plaques and accumulates in vessel walls as CAA

Question 25

genetic risks for alzheimers

Answer 25

ApoE4 allele is the only recognised risk factor familial form - mutations in presenilin 1 or presenilin 2 leading to early onset alzheimers trisomy 21 - alzheimers by 35yrs

Question 26

diagnostic criteria fro AD

Answer 26

ABC score thal phase - of amyloid plaques (beta-amylloid stain) braak stage - of neurofibillary tangles (tau AT8 stain) CERAD stage of neuritic plaques (bielschowsky stain)

Question 27

frontotemporal lobar degeneration (FTLD)

Answer 27

pathological correlate of FTD progressive frontal lobe dysfunction that may be followed by temporal lobe symptomatology behaviour and language problems precede memory problems onset younger than for alzheimers

Question 28

FTLD is divided by

Answer 28

divided into several subgroups that are distinguished according to type of protein deposited on immunohistochemistry (Tau, TDP-43, FUS, UPS)

Question 29

FTLD macroscopic

Answer 29

severe frontotemporal atrophy variable other findings pallor of pigmented nuclei in the brainstem in some entities

Question 30

NDD with clinical features of parkinsonism

Answer 30

several different disease affecting the same circuitries in the network of neurones in the brain can result n similar clinical findings many of these movement disorders are sassociated with dementia only able to be distinguished on neuropathological examination

Question 31

clinical features of parkinosnism

Answer 31

``` head bent forward tremors of the head mask-like facial expression drooling rigidity stooped posture weight loss tremor akinesia loss of postural reflexes done demineralization shuffling and propulsive gait bradykinesia pill-rolling tremor festinant gait ```

Question 32

causes of parkinsonism

Answer 32

``` parkinsons disease dementia with lewy bodies multiple system atrophy tauopathies trinucleotide repeat diseases symptomatic parkinsomism - toxic eg. carbon monoxide, carbon sulphide, manganese drug induced - butyrophenones, phenotiazines, fluraridine, reserpine vascular parkinonsim ```

Question 33

synucleinopathies

Answer 33

alpha-synuclein found to be major component in several cytoplasmic inclusions protein involved in synaptic transmission

Question 34

dementia with lewy bodies

Answer 34

2nd most common dementia, 10-25% of cases fluctuating cognitive impairment, visual hallucinations, parkinsonism autonomic dysfunction sleep difficulty - REM sleep behaviour disorder depression apathy DLB = cognitive impairment first, movement later

Question 35

huntington disorder

Answer 35

``` AD movement disorder - hyperkinetic degeneration of the striatum relentless progression CAG trinucleotide repeat anticipation ```

Question 36

progression of huntington disorder

Answer 36

early cognitive symptoms, mood disorder progression to severe dementia death in 15 years on average

Question 37

the prion hypothesis

Answer 37

PrPc is a normal cellular tranmembrane protein of uncertain function prion disease is due to an abnormally folded form of the protein (PrPsc) with has a tendancy to aggregate in the ECS and causing spongiform change

Question 38

creutzfelt jakob disease

Answer 38

most common prion disease myoclonus and characteristic EEG changes occur late can be inherited as AD trait, can bbe acquired by tranmission or occur spontaneosly

Question 39

tranmission of cruetzfelt jakob disease

Answer 39

person to person tansmission requires parenteral innoculation of infected tissue (iatrogenic) - incubation period ranges from years to decades

Question 40

diagnosis of cruetzfelt jakob disease

Answer 40

requires histology

Question 41

CJD autopsiess

Answer 41

requires special decontamination procedurres | needs full PPE and self contained breathing devices

Question 42

CJD histology

Answer 42

microscopic vacuolaton of gray matter - spongiform change extra cellular accumulation of protease resistant peptide (PrP - prio protein) neuronal loss and gliosis