Behavioral Science - dementias (combined lectures) Flashcards by B -

What defines MCI vs normal aging?

MCI must have:
Memory complaint corroborated by an informant
Objective memory impairment for age and education
Preserved general cognition
Normal activities of daily living
Not demented

normal aging:
Difficulty retrieving words and names
Slower processing speed
Difficulty sustaining attention when faced with competing environmental stimuli
Learning something new takes a bigger effort
No functional impairment

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DSM criteria for dementia (Neurocognitive Disorder):

1) decline in memory, complex attention, exec function, learning/memory, language, perceptual/motor, social cognition
2) Cognitive deficits must impact social and occupational function
3) Diagnosis must be made in the presence of intact sensory systems

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two DSM5 suptypes of neurocognitive disorder

Meets 3 criteria (decline, social/ocupational impact, not due to focal neurological defecit in sensory systems)

MAJOR patient not capable of independent living
MINOR capable of independent living

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When does early onset AD present? Late onset?

30 - 60 Yrs of age

>60

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Is early onset AD usually sporadic or familial?

familial (older than 60, cases are much more likely to be sporadic)

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What are the associated genetic mutations in early onset AD? Genetics (sex linked, autosomal, recessive, dominant)?

1- abnormal presenilin 2
14- abnormal presenilin 1
21- abnormal amyloid precursor protein

Autosomal dominant

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What chromosome is APOE4 located on?

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What is AD? How does it usually present clinically?

The most common cause of senile dementia.

presents with deficits in recent memory, progressing to global impairment of cognition.

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What is a hallmark feature of AD suspected to account for clinical symptoms?

Neuronal and synaptic loss affecting cortical and some subcortical areas (e.g. nucleus basalis of Meynert).

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Which type of neuron is thought to contribute to loss of cognitive function in AD?

cholanergic neurons

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What enzymes is responsible for cleaving APP?

beta and gama secretase

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What enzymes is responsible for cleaving APP?

beta and gama secretase

beta secretase is also called BACE1 (Beta-site APP Cleaving Enzyme 1)

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A-beta deposits in cortical and leptomeningeal arteries and arterioles - disease?

cerebral amyloid angiopathy

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development of abnormal proteinaceous (alpha-synuclein) cytoplasmic inclusions

Lewy bodies

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what is Granulovacuolar degeneration (GVD) - what disease?

grainy deposits within neurons surrounded by a clear zone

AD (also lewey body dementia but LBD is often associated with AD hippocampal features)

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what is Granulovacuolar degeneration (GVD) - what disease?

grainy deposits within neurons surrounded by a clear zone

AD (also lewey body dementia but LBD is often associated with AD hippocampal features)

Because of association with other dementias GVD and also Hirano bodies are not considered diagnostically important disease features

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rapid or acute onset dementia, with especially rapid decline in the first few months - overlapping loss of cognitive and motor function, diffuse alpha-synuclein rich cytoplasmic inclusions throughout the brain (cortex and basal ganglia), sometimes cortical atrophy/ventriculomegaly, loss of Ach and DA neurons (in SN not VTA)

Lewy body dementia

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Presinilin (what, where is it?)

component of gamma secretase complex (multimeric transmembrane protein complex responsible for cleaving the membraine associated region of amyloid precursor protein)

forms the catalytic/proteolytic site - mutations of presenlin 2 (chromasome 1) and preseilin 1 (chromasome 4) are involved in familial AD

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Presinilin (what, where is it?)

component of gamma secretase complex (multimeric transmembrane protein complex responsible for cleaving the membraine associated region of amyloid precursor protein)

forms the catalytic/proteolytic site - mutations of presenlin 2 (chromasome 1) and preseilin 1 (chromasome 14) are involved in familial AD

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1st and 2nd greatest risk factors for AD

Age, APOE4

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Which APOE allele is thought to be protective against AD?

APOE 2

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dense central core of compact amyloid, surrounded by a clear zone and a peripheral corona or halo consisting of non-compact amyloid and neurites, including axon terminals

neuritic/senile plaque

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Apple-green birefringence of what stain under polarized light confirms presence of amyloid.

congo red

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stain for neurofibrillary hyperphosphorylated tau tangles

silver

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what is Tau? What is it's function?

microtubule associated protein - stabilizes microtubules

How are neurofibrillary tangles formed?

hyperphosphorilation by microtubule associated kinases result in deassociation with MT fillament, MT depolimerization, and assemblage of hyperphosphorylated tau into paired helical filaments, which bundle to form neurofibrillary tangles

what are neuropil threads?

the dystrophic neurites at the periphery of neuritic plaques - major component is paired helical filaments of hyperphosphorylated tau

What are the gross features of Frontotemporal Lobar Degeneration as seen in frontotemporal dementia?

atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes. has so-called knife edge

what are the common accumulation products seen in frontotemporal lobular dengeneration/frontotemporal dementia?

*FTLD-Tau (Numerous tau containing neurons) Most common *FTLD-TDP (TAR-DNA binding protein 43) FTLD-FUS and other (less common)

Relative to AD what is the onset profile for FTD?

Earlier onset compared to AD

What are Pick bodies? What diseases are they associated with? Where are they seen?

intraneuronal inclusions of Tau AD and FTD Dentate gyrus of hippocampus

What are the stages of AD?

asympomatic, podromal (early, possible disease sympotms),

What are early cognitive symptoms of AD?

Trouble keeping appointments Difficulty finding words Misplacing objects

What are early functional symptoms?

Difficulty driving Difficulty selecting clothes Missing appointments Problems at work

cognitive retardation from primary depression and dementia differ in that depressed patients usually 1 2 3

Demonstrate less motivation during cognitive testing Express cognitive complaints that exceed measured deficits Maintain language and motor skills

What are the indications for neuroimaging in a suspected demented patient? 1 2 3

Focal findings on exam Rapid onset/decline Falls, head trauma by history

What are 3 common features seen in both vascular dementia and AD?

Lacunar infarcts, small vessel disease white matter

Compared to AD, memory loss in FTD occurs earlier or later in the disease course?

later! (earlier onset in FTD and more rapid progression, but behavioral/emotional changes, not memory impairments, are not the initial clinical findings)

Are cholinesterase inhibitors useful for FTD?

What medication can help with behavioral control in FTD patients?

(anticonvulsants) Divalproex or valproic acid

Are SSRIs used for FTD?

yes - for irratability, depression, impulsive behaviors

Can atypical atipsychotics be used?

Yes, carefully

What are the most common pharmacologic treatments for AD?

Cholinergic therapy. | NMDA receptor antagonists

Are current pharmacologic treatments disease modifying based on biomarkers (CSF-Tau Amyoid/FDG-PET?)?

no - for management of cognitive/behavioral symptoms symptoms

Degeneration of ______ results in "Inwide-spread" of acetylchoiline deficiency in AD

the basal nucleus of Meynert

memory deficits in AD are thought to be caused by_____?

Loss of Ach neurons

Which class of agents and which drugs in particular are used to address consequences of degeneration in the basal nucleus of Meynert in AD?

anticholinergic agents donepezil rivastigmine galantamine

What drug is FDA approved for treatment of severe AD?

donepezil - AChE inhibitor - metabolized by CyP450 - side effects are nausia, vomiting, sleep disturbance

What neurodegenerative disease is memantine used for an why (pathophysiology of neuronal death/ drug MOA)?

AD - because loss of cholanergic neurons and symptoms cascade is thought to be caused by glutamatergic excitotoxicity thinking is that excess glutamate signaling results in excess Ca 2+ influx into cytoplasm and activation of signalling pathways that lead to increased expression of phosphatases/kinases, which in turn disrupt microtubule stabiizing proteins and form intracellular filament aggregates that alter metabolic function and damage mitochondria triggering apoptosis memantine is an NMDA receptor antagonist

Can memantine be used alongside donepezil?

yes - combo of AChE blocker + NMDA blocker is most beneficial

which antidepressants are used for AD?

sertraline and venlafaxine

What anxiolytics are used for AD?

buspirone and lorazepam.

what antipsychotics are used for AD?

risperidone and haloperidol

Multi-infarct dementia

diffuse small infarctions that result from small vessel disease and lead to neuronal death and cognitive decline feature of vascular dementia

what are the common histologic features of vascular dementia?

diffuse lacunar infarcts caused by hypertension related small vessel pathology white matter pathology neuronal death cerebral amyloid angiopathy

What is a leukoencephalopathy? What type of dementia is it commonly associated with?

broad term that describes any disease that affects brain white matter (leuko = white) common in vascular dementia

What vessel branches are particularly susceptible to hypertensive small vessel pathology?

branchges of lenticulostriate arteries that supply basal ganglia and internal capsule

what form of dementia can result from arteriosclerosis of small arteries?

subcortical dementia

what are features of subcortical dementia

Cognitive slowing. Impaired problem solving. Visuospatial abnormalities. Disturbances of mood and affect

How common is vascular dementia relative to other dementias?

Most common after Alzheimer’s

Progression of vascular dementia is usually _____

Step-wise - but can be abrupt after CVA

what is a common association with vascular dementia?

cardiovascular risk factors - atherosclerosis, hypertension, hyperlipidemia, diabetes

T/F “Mixed” dementia with AD or Lewy Body is not unusual

true

T/F emotional lability (inapropriate ouburst of crying/laughing) is a common feature of subcortical vascular dementia

true

T/F first line pharmacologic treatment for vascular dementia is anticholanergic agents

false! cholinesterase inhibitors are used to increase Ach | donepezil, glalantamine, rivastigmine

T/F exercise (both physical and mental) is useful in treatment of vascular dementia

true

T/F a "Mediterranean" diet is recommended for prevention/treatment of vascular dementia

true

T/F focus of vascular dementia is control of cardiovascular risk factors

true

what primary sporadic diseases are caused by intracellular missaccumulation of pre-synaptic protein alpha-synuclein?

parkinsons disease lewy body dementia

what is the site of apearance of lewy bodies in lewy body dementia vs parkinsons disease

``` LBD = cortex Parkinsons = SN ```

What are the cardinal symptoms are parkinsons disease?

``` resting tremor, difficulty initiating movement (akinesia), slowed movement (bradykinesia), rigidity, shuffling gait postural instability. ```

parkinsons disease ever associated with dementia

yes, occasionally (probably underdiagnosed)

Pallor of substantia nigra with degeneration and loss of pigmented dopaminergic neurons of substantia nigra pars compacta (SNpc) that contain eosinophilic inclusions called lewy bodies what disease?

parkinsons

palor of substantia nigra with degeneration or loss of substantia nigra pars compacta without lewy bodies is seen in what disease?

cortical basal degeneration or progressive cerebral palsy

What are the 2 features necessary for making histologic diagnosis of parkinsons disease?

palor of substantia nigra with lewy bodies!

what is more common fronto temporal dementia or lewy body dementia?

lewy body dementia (3rd most common)

T/F dual diagnosis of AD and LBD is possible

true

T/F lewy body dementia can be associated with little or no atrophy

true

What is a hallmark and distinctive feature of lewy body dementia?

visual hallucinations with significant cognative fluctuations from day to day

T/F antypsychotic drugs are used to address conitive/behavioral fluctuations in LBD

False! antipsychotics are contraindicated due to increased sensitivity

What drug is used to treat REM sleep disorder in LBD?

clonazepam

what is the diagnostic criterion used to difference between LBD and PD?

uses time frame of appearance of parkinsonian symptoms

Onset of dementia within 12 months of parkinsonism

LBD

Onset of dementia more than 12 months after the diagnosis of PD

PD (w/ dementia)

what is the Mini Mental Status Examination (MMSE)?

Standardized 30 point rating scale that SCREENS (does not diagnose) for dementia

What factors can influence the MMSE results?

age, education, ethnicity

T/F a higher number (1-30) indicates more severe cognitive impairment

False low numbers are worse

how is the MMSE result categorized?

normal mild moderate severe

MMSE of 20-10

possible moderate dementia

What are early behavioral symptoms?

Subtle changes in personality Social withdrawal Depression

MMSE score categorizing possible severe dementia

Cognitively normal person's MMSE score

30-27

possible mild dementia MMSE score

30-20

T/F MMSE scores can be used to discern the type of dementia

False - only severity

What are the 5 categories of the MMSE?

``` Orientation Registration Attention and Calculation Recal Language ```

What is the MoCA?

Montreal cognitive assessment Standardized 30 point rating scale Screening tool … NOT a diagnostic tool Not specific for dementia type Scoring- can be impacted by age, education, ethnicity

What is different about the MoCA and MMSE

Catagories and scoring MoCA is more sensitive

What are the catagories of the MoCA?

``` Misuospatial/executive naming memory attention language abstraction delayed recal orientation (optional) ```

Is it possible to get a 30 on the MMSE and still have dementia?

yes (mild 30-20) -- also test is NOT diagnostic

What is the mini-cog? How is it performed? Interpreted?

stripped down version of MMSE As Pt. to repeat 3 unrelated words (mushroom cannon flamingo) then ask them to draw a clock showing a particular time then ask to repeat words Interpretation is subjective - if they have some difficulty on either they probably have some degree of cognitive impairment

What is the scoring system on the MoCA?

Normal >26 Mild 18-26 Moderate 10-17 Severe

What is included on the MoCA that is missing from MMSE?

assessment of executive function

How does the MoCA assess working memory?

ask Pt. to repeat reverse number sequences

What categories are functional assessment divided into?

ADLs - activities of daily living IADLs - instrumental activities of daily living (allow people to engage with their environment and facilitate daily needs)

ADL or IADL? ``` Dressing Eating Ambulating Toileting Hygiene ```

ADL ``` D E A T H ```

ADL or IADL? ``` Shopping Housekeeping Accounting Food Preparation Transportation ```

IADL ``` S H A F T ```