wk 13, lec 1 Flashcards
dementia definition
- Memory impacted most, cant perform daily activities
risk factors for dementia
o Under 45: lower education, less cognitive reserve
o Hearing loss; temporal lobe decrease in volume (hippocampus + entorhinal cortex)
o Traumatic brain injury (TBI): hyperphosphorylated tau
o Hypertension: decreased brain volume, increase white matter
o Alcohol: prolonged abstinence is bad; right sided hippocampal atrophy
o Obesity
o Smoking
o Depression
o Social isolation: social is goof for cognitive reserve
o Physical inactivity: CVD morbidity
o Air pollution: increase AB deposition and amyloid precursor protein
o Diabetes: T2D
pathogenesis of dementia
o Memory impairment: cerebrum, diencephalon and medial temporal lobes
o Impaired language: perisylvian parts of dominant frontal, temporal and parietal lobes
o Loss of reading and calculation: posterior left (dominant) cerebral hemisphere
o Loss of gestures (apraxias): dominant parietal region
o Impaired drawing: parietal lobe on non dominant (right side)
o Behaviour and personality- frontal lobe
degenerative types of dementia
o Cerebral cortex, diencephalon, basal ganglia
o Thalamus and cerebral cortex= memory
o Alzheimers damages hippocampus and cholinergic nuclei
inclusions in dementia
o Intracellular inclusions
o Disrupt normal protein homeostasis
o Stress response inclusions
CHART TO DIFFERENTIATE THE DISEASES
what inclusions are in Parkinson’s and dementia with Lew bodies
alpha synuclein
what inclusions are in frontotemporal dementia
tau
what inclusions in alzheimers
beta amyloid and tau
arteriosclerotic cerebrovascular disease contributing to dementia
- Multiple infarcts to thalami, basal ganglia, brainstem, cerebrum affects motor, sensory and visual
- Recurring strokes cause multi-infarct or vascular dementia (not just the arteriosclerosis)
severe cerebral trauma lesions
- In frontal and temporal poles, corpus callosum and thalamus
- Disrupt white matter; axonal shearing or diffuse axonal injury
- Chronic hydrocephalus
inflammatory conditions can contribute to dementia
- Inflammatory and loss of neurons- syphilis, cryptococcosis, chronic meningitides, viral infections (HIV, herpes)
prions disease
widespread loss of cortical neurons, gliosis, spongiform changes
leukodystrophy
manifests as subcortical dementia; White matter lesion from advances MS, multifocal leukoencephalitis, or vascular dementias
how are proteins impacted in dementia
- Sequester proteins and macromolecules and make them ineffective- physically obstruct axons, dendrites and movement of material in cytoplasm- disrupt homeostasis and protein recycling
- Aggregated proteins form ultrastructural fibrils cytotoxic
- Revolve around proteostasis, folding and degradation of proteins…
what is found in alzheimers
beta amyloid and tau
who does alzheimers occur in
- Most common form of dementia in elders
- Women 2x
most common type of dementia in elders
AD
findings in AD
- Cortical atrophy (parahippocampal region) and hydrocephalus ex vacuo
-neuritic plaques
-neurofibrillary tangles
brain changes in AD
- Gyri narrow, sulci widen, ventricular enlargement, reduced brain weight
neuritic plaques (sensile plaques) in AD
o Affect gray matter, reactive astrocytes and microglia, distorted neuronal processes, beta amyloid plaques
o Quantity and distribution of plaques don’t closely algin with severity
neurofibrillary tangles in AD
o Polymerized tau filamants intracytoplasmically
o Can have these tangles in entorhinal cortex and parahippocampal gyrus and be asymptomatic, years before developing AD
intracellular vs extracellular changes in AD
- Intracellular neurofibrillary tangles with hyperphosphorylated tau
- Extracellular amyloid plaques with beta amyloid core (from amyloid precursor proteins, APP)
3 sites the amyloid precursor proteins undergo hydrolysis in AD
o APP undergo hydrolysis at three sites: alpha, beta and gamma secretase
Alpha secretase produces non-toxic peptides
Beta and gamma secretase generate toxic peptides
which of alpha, beta and gamma secretase; which are toxic and non-toxic
Alpha secretase produces non-toxic peptides
Beta and gamma secretase generate toxic peptides
which ion is impacted in AD
- Toxic polypeptides aggregate extracellular and adhere to AMPA receptors and Ca2+ channels Ca2+ influx
clinical features in AD
o Progressive memory and cognitive decline and language and behavioural alteration
o Common medical complications such as bronchopneumonia, urinary tract infections, and pressure ulcers often contribute to mortality.
3 stages of AD
presymptomatic
mild cognitive impairment
AD
- Presymptomatic: accumulation of extracellular beta amyloid and tau tangles in hippocampus and temporal cortex; no cognitive impairment
- Mild cognitive impairment (MCI): not affecting ADL; low levels of CSF beta amyloid 1-42 or elevated amyloid load on PET scan
- AD: neurophysiological evaluation
what are the accumulates in picks disease (frontotemporal dementia) and how does it differ from alzheimers
- Accumulate tau (NOT beta amyloid- so differentiate from AD)
what are the changes seen in picks disease (frontotemporal lobe dementia) to functioning and how does it differ than alzheimers
- Also starts with disruptive and inappropriate behaviour (not memory like AD)
causes of picks (frontotemporal dementia)
- Majority are sporadic, but also 40% have hereditary component
2nd most common cause of early onset dementia < 65 years old
Pick disease (frontotemporal lobe dementia; FTLD)
knife edge atrophy in Pick disease (frontotemporal lobe dementia; FTLD)
- Cortical atrophy in frontotemporal regions, reduced and thin silvers gyri
changes in Pick disease (frontotemporal lobe dementia; FTLD)
- Loss of neurons and astrogliosis
what are picks bodies
- Residual neurons are argentophilic (silver) and tau-immunoreactive round cytoplasmic inclusions = Picks bodies
3 subtypes of Pick disease (frontotemporal lobe dementia; FTLD)
- behavioural variant
- Primary progressive aphasia (PPA) – semantic variation
- Primary progressive aphasia nonfluent/agrammatic variant
Behavioural variant (bvFTD) of Pick disease (frontotemporal lobe dementia; FTLD)
Apathy, disinhibition, impaired judgement, loss of empathy, eating disorders
Compromised insight, compulsive behaviours, depression
o Primary progressive aphasia (PPA) – semantic variation of Pick disease (frontotemporal lobe dementia; FTLD)
Decline in capacity to comprehend words, objects, individuals, and emotions
o Primary progressive aphasia nonfluent/agrammatic variant of Pick disease (frontotemporal lobe dementia; FTLD)
Impaired motor speech and word generation
Motor neuron disease can accompany any of the subtypes
progression of Pick disease (frontotemporal lobe dementia; FTLD)
3-10 years leads to death
2 types of lewy body dementia
Parkinson and dementia (PDD) or Lewy body disease (LBD)
what do Parkinson and dementia (PDD) or Lewy body disease (LBD) both have
o alpha synuclein aggregates in neurons and glia= synucleopathies
o both have executive, attentional, visuospatial deficits
o episodic memory is relatively preserved
o prodromal phase of mild cognitive deficits
what is relatively perserved in Lewy body dementia
episodic memory
aggregate in Lewy body dementai
alpha syncline
what is absent in Lewy body dementia
- Lewy body inclusions and absence or limited # of neurofibrillary tangles and amyloid plaques
factors for Lewy body dementia
- Genetic and environmental factors
lewy bodies
intraneuronal cytoplasmic inclusion of straight neurofilaments
o Bodies contain epitopes recognized by antibodies against phosphorylated and non-phosphorylated neurofilament proteins ubiquitin and alpha synuclein
Lewy body found in
brainstem, substantia nigra, amygdala, cingulate gyrus, neocortex
3 stages of Lewy body dementia
- Brainstem predominant
- Transitional limbic
- Diffuse neocortical
what does the cholinergic deficit in Lewy body dementia cause
inattention, character fluctuations and visual hallucinations
progression of Lewy body dementia vs Parkinson dementia
LBD- - Get motor and dementia at the same time or dementia before the motor
- Affect ADL from cognitive decline more than Parkinson’s
PD- - Motor symptoms first and then get dementia
brain areas in parkinson
- Limbic and cortical areas
what symptoms in Parkinson’s
- Non motor (constipation and hyposomnia) then anxiety, depression, REM sleep behaviour disorder, parkinsonism then dementia
diagnose Lewy body dementia
- Diagnosis: Psychosis, visual hallucinations, REM sleep disorder, parkinsonism
early sign of Lewy body dementia
- REM sleep behaviour disorder is often prodromal (early sign)
which dementia do you get - Anosmia (loose smell)
Lewy body dementia
what must occur to have vascular dementia
- 1+ symptomatic strokes
- Asymptomatic vascular lesions
stroke impact on cognition
- ½ stroke survivors have cognitive impairment
large vs small cerebral strokes and vessel disease
- Large cerebral strokes
o Symptomatic strokes, ischemic or hemorrhagic damage the cerebral cortex, white matter, and infratentorial structures - Cerebral small vessel disease
o Lack of symptoms
o Arteriosclerosis and cerebral amyloid angiopathy (beta amyloid plaques on walls)
vascular dementia influence on concurrent brain pathologies
o BBB compromised; infiltrate neurotoxic or inflammatory agents
hearing impairment and dementia
- Sensorineural hearing loss in elders
- Mild cognitive impairment and AD
4 theories of hearing impairment and dementia
o Increased cognitive load (more effort to process speech)
o Changes in brain structure and function (decrease brain volume and primary auditory cerebral cortex)
o Common pathological conditions; degenerate stria vascularis, lose hair cells, primary afferent neurons
o Social disengagement and isolation
traumatic brain injury and dementia
- Cerebrovascular dysfunction
gut microbiome and dementia
- Obesity, diabetes, cancer, autoimmune, depression
- Beta amyloid, tau phosphorylation, neuroinflammation, neurotransmitter dysregulation, oxidative stress
Which of the following neurodegenerative diseases is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain?
- A) Vascular dementia
B) Lewy body dementia
C) Frontotemporal dementia
D) Alzheimer’s disease
D) Alzheimer’s disease
Which type of dementia is associated with motor symptoms such as tremors, rigidity, and bradykinesia?
- A) Alzheimer’s disease
B) Vascular dementia
C) Lewy body dementia
D) Parkinson’s dementia
D) Parkinson’s dementia
Which type of dementia is associated with a gradual decline in cognitive function due to multiple small strokes or impaired blood flow to the brain?
A) Alzheimer’s disease
B) Vascular dementia
C) Lewy body dementia
D) Frontotemporal dementia
E) Parkinson’s dementia
B) Vascular dementia
