dementia and alzheimers✅

Dementia

global deterioration of intellectual function in the face of unimpaired consciousness

neuropsychological

Most deficits of dementia are found in what objective exam

insight

A key aspect of dementia and the reason all individuals with dementia are brought in my someone else is a loss of

3-object recall

at an interval of 1, 5, and 10 min recall the list of objects you were told to remember (Memory)

serial 7's

ask the patient to subtract serial "7s" from 100, depends on intact working memory in the frontal lobe (Attention and Concentration)

parietal, temporal and frontal

often dementia effects what regions of the brain

visual spatial

This aspect of intelligence is affected by dementia of the parietal lobe

Primitive reflexes

behaviors that return in dementia related to frontal cortex

Anterior Dementia

Behavioural changes/loss of inhibition, antisocial behaviour, facile and irresponsible

Frontotemporal dementia (Pick's), Huntington's disease.

Anterior Dementias occurring in Frontal pre-motor cortex (2)

Posterior dementia

disturbance of cognitive function without marked changes of behaviour

Alzheimer's disease

Posterior Dementia occurring in Parietal and Temporal Lobes

Weeks

Encephalitis progresses in what time frame

Months

Creutzfeld-Jacob's disease progresses in what time frame

years

Normal pressure hydrocephalus's progresses in what time frame

decades

Alzheimer's disease progresses in what time frame

Degenerative

Cause of dementia involving disfunction of neurons and glial in ways we don't understand, include Alzheimer's, Lewis Body dementia, Tauopathies, Huntington's, Parkinson's, Wilson's

Tauopathies

Class of neurodegenerative diseases involving aggregation of abnormal Tau protein (frontal temporal)

Wilson's disease

hepatolenticular degeneration (copper accumulation & decrease in ceruloplasmin)

Structural

Cause of dementia including Normal pressure hydrocephalus, brain tumors, head injuries and subdural hematoma

Cerebrovascular

Cause of dementia including vascular dementia(muti-infarct dementia) and CNS Vasculitis

Infection

Cause of dementia involves rapid degeneration in response to it including Creutzfeld- Jacob Disease, Neurosyphilis, HIV, Viral encephalitis (Herpes)

Toxic/Metabolic

Cause of dementia including drug induced, alcoholism, toxin+heavymetals+CO, vitamin deficiencies, Hypothyroidism, Uremia +dialysis related, Hepatic encephalopathy

B12, Thiamine, and Folate

Vitamin deficiencies associated with dementia

Immune Disorders , and Cancer

Cause of dementia including Lupus, and Paraneoplastic disease

Depression

Highly associated condition with dementia (correlation not causation)

Alzheimer's disease

a progressive and irreversible brain disorder characterized by gradual deterioration of memory, reasoning, language, and, finally, physical functioning

70-80%

Alzheimer's causes what percent of dementia

7-9%

Canadian population over 65 with AD

35.5

Canadian population over 85 with AD

4.5 million

number of people in US and Canada w AD

Symptoms of Alzheimer's

impairment of memory &attention, language & communication, abstract thinking , judgement, personality changes, depression, and visuo-spatial disorientation (difficulty orienting in space)

Sign's of Alzheimer's

motor and gait disturbance, poverty of movement and slowness, falls, problems with bladder and bowel control, seizures(usually occur later)

late 60's or later

Alzheimer's occurs

10%

Familial forms of Alzheimer's account for what percent of cases

90+%

Sporadic forms of Alzheimer's account for what percent of cases

early onset (40-50)

associated timing of familial Alzheimer's

late onset (60+)

associated timing of sporadic Alzheimer's

Presenilin 1 & 2

main susceptible gene for early onset Alzheimer's (APP)

Apolipoprotein E4 gene

main susceptible gene for late early Alzheimer's

Cortical atrophy
Synaptic and neuronal loss
Neurofibrillary tangles (NFTs)
plaques with amyloid core
Amyloid angiopathy

Neuropathological effects of Alzheimer's Disease

beta-amyloid plaques

dense deposits of protein and cellular material that accumulate outside and around nerve cells

neurofibrillary tangles

twisted fibers that build up inside the nerve cell

Amygdala>Hippocampus>Inferior Temporal Lobe> Parietal Lobe > Occipital lobe > Frontal Lobe

Distribution of amyloid deposition in the human brain most to lease

superior temporal lobe, cerebellum, pre and post central gyri

Regions of the brain that are relatively free of amyloid deposition

Amyloid Precursor Protein (APP)

membrane protein that sits in the membrane and extends outward. It is though to be important for neuronal growth, survival, and repair

secretases

cut the APP into fragments, the most important of which for AD is called b-amyloid (beta-amyloid) or Ab

Beta-amyloid

"sticky" so the fragments cling together along with other material outside of the cell, forming the plaques seen in the AD brain and is toxic to neurons

Tau protein

normal role is to aid axonal trafficking of molecules through its association with microtubules
In AD it is abnormally phosphorylated through the action of many kinases causing it to dissociate from microtubules and form paired helical fragments, this deposition impairs axonal transport
Upon cell death these fragments aggregate to produce extracellular neurofibrillary tangles, which may be linked with Aβ

acetylcholine

In AD there is a decrease in chemical messengers in the brain esp.

Occipital, Frontal, and Parietal cortex

Cholinergic Basal Forebrain and its connections project where

amyloid vaccine, secretase inhibitors, anti-amyloid agents, drugs that lower cholesterol

Possible treatments for AD (4)

estrogens, NSAIDs, vasodilators, propentofylline

Unproven treatments for AD (4)

Higher education, Intellectual stimulation, exercise and diet, (red wine)

Non-drug approaches for treating or reducing risk of AD (3+(1))

hippocampus

AD leads to atrophy of what critical brain region in particular

Dementia with Lewy Bodies

dementia involving visual hallucinations, cognitive fluctuations in attention and alertness, and atypical movements (Parkinsonian)

cholinesterase inhibitors, antipsychotic drugs

Treatment for Dementia with Lewy Bodies (2)

loss of pigment is substantia nigra (PD and DLB) and lewy bodies (containing alpha-synuclein protein)

In dementia with lewy bodies 2 pathological signs are

Frontotemporal Dementia (Pick's Disease)

female preponderance and at a younger age than AD,
atrophy of the frontal lobes that eventually progresses to include the temporal lobes,
early personality and behavioral changes (disinhibition, apathy, perseveration, mental rigidity and affective symptoms)
Tau pathology most frequently observed

17

Frontotemporal Dementia (Pick's Disease) has a familial form associated with chromosome __

ALS or Lou Gehrig's disease

Frontotemporal Dementia (Pick's Disease) can be associated with

Vascular Dementia (VaD)

A form of dementia characterized by sporadic, and progressive, loss of intellectual functioning caused by repeated infarcts, or temporary obstructions of blood vessels, which prevent sufficient blood from reaching the brain. (Also called multi-infarct dementia.)

10-15%

Vascular Dementia (VaD) accounts for what percentage of dementia

hypertension and other vascular risk factors

Vascular Dementia (VaD) treatment involves treating