Psyc 357 Week 5 - Dementia

Aging on digestive system

Minimal

Tau

Protein making up neurofibrillary tangles. Play role in maintaining stability of microtubules that form internal support structure of axons. Train tracks guiding nutrients form scell body to ends of axon. Tau proteins like railroad ties.

DIet alzheimers

Rich in antioxidants

Brain shrinkage alzheimers

Start with hippocampus, neurons die

Disease rates increasing over time

We are just getting better at diagnosing it

Acetylcholinesterase

alzheimers medications target. Enzyme that normally destroys acetylcholine after release into synaptic cleft. Reduces acetylcholine available to hippocampal neurons, lead to memory loss. Treatment inhibits enzyme. Slow breakdown of acetylcholine, maintain at normal levels.

Polypharmacy

prescribed medications given in too strong a dose or harmful combinations can cause neurocognitive disorder-like symptoms. Take multiple drugs, can be particularly lethal. Older more vulnerable because excretion of medications slower.

Frontotemporal neurocognitive disorder

(FTD): specifically involves frontal lobes of brain. Personality changes such as apathy, lack of inhibition, obsessiveness, addictive behaviors, and loss of judgmeent. Eventually neglect personal habits, lose ability to communicate.

Metabolic syndrome diagnosis requriement

3/5 only

Deceased football players

99% show signs of CTE. Most former offensive or defensive linemen (repeated minor concussions).

CTE study 18 yo deaths

: saw startings of CTE after injury not even concussion. Start as early as 24 hours after injury.

Support for caregivers

: taught ways to promote independence and reduce distressing behaviors in patient, and heandle emotional stress on them.

Caregivers

: the individuals, uusally family, who provide support to people with chronic diseases. Very likely to suffer adverse effects from constant demands placed upon them.

SEcretases

: trim outer part of APP in healthy aging. Flush with neurons outer membrane. IN Alzheimer's, this doesn't work, snip at wrong place.

Charting course of AD

AD brain changes start decades before symptoms show. Memory problems but brain is ok to compensate in midlife. Significant cognitive decline around 75-84 ish, much more than usual aging.

Amyloid hypothesis

AD brain contain increasing numbers of beta amyloid plaques over time. We know they proceed clinical symptoms. Sporadic AD patients have decreased clearance of amyloid. Pressenillin genes abnormally process APP, resulting in 50% increase in beta amyloid peptides, which aggregate for form neuritic plaques. Down's connection. Amyloid is neurotoxic.

Auguste Deter

Alzheimer's diagnosis. In 50s, treated progressive mental deterioration, increasing confusion and memory loss. Noticed odd disorganization of nerve cells in cerebral cortex.

APP Gene

Chromosome 21. Appears to control production of APP, protein that generates beta-amyloid.

Differences between MID and alzheimers

Development of MID more rapid

Epidemiology alzheimers 2 types

Familial: early onset or late onset, estimate that 50% of dominantly inherited disease remains to be mapped. Dominantly inherited, you get the gene you get Alzheimer's. Sporadic: late onset, vast majority, always late onset, multiple genetic and environmental influences, vulnerability genes. Not definitive.

Lifestyle study alzheimers

Follow almost 2000 for 10 years. Examine adherence to Mediterranean diet, exercise,a nd time to incident AD. High diet and physical activity, risk reduction by 35-44%.

Environmental causes of alzheimers

Lifestyle Twin data: if you have a twin you will get it, but might not be same age. Japanese Men move to Hawaii: Japanese men have lower risk of Alzheimer's. If moved to Hawaii, had same risk as everyone else living in Hawaii. Nun Study Mental Activity: some of most powerful evidence. Autopsy, significant number showed no behavioral symptoms but had high percentage of plaques and tangles. Head Injury: severe injuries involving loss of consciousness, causes damage to neurons. Additive w/ ApoE4.

Caregiver strategies

Max patients independence for as long as possible. Reduce/eliminate frequency of actions like wandering or being aggressive with behavioral strategies - ignore behaviors to not reinforce. Operate to strict daily schedule. Identify situations where patient becomes disruptive, identify aspects of situation, modify.

Environmental contributions alzheimers

Nuns: despite appearance of plaques and tangles on autopsy, many didn't show symptomatic deficits. Higher mental activity in early adulthood seemed to protect form signs of cognitive decline later in life despite changes in brain. Exercise - Japan study, highly active older adult lower rate of alzheimers

Severity of Amyloid plaquest

ONly weakly associated with severity of disease

Genes in Alzheimers (3)

Presenilin (PS1 & 2), APP Gene, ApoE Abnormalities

Vascular neurocognitive disorder risks

Similar to cardiovascular

Amyloid Plaques

abnormal deposits of protein fragments. Insoluble. Beta-amyloid-42 (42 amino acids). From fragments cut off of APP.

Delirium

acute cognitive disorder, temporary confusion. Cause by disease of heart and lung, infection, or malnutrition. Sudden onset. Require immediate medical attention. Many causes. Most cases subside within days. If misdiagnosed with dementia, lose treatment op. Institutionalized settings: onset associated wtih presence of pain and use of antipsychotic meds.

Wernicke's diesease

acute condition, caused by chronic alcohol abuse. Delirium, eye movement disturbances, difficulties maintaining balance and movement, deterioration of nerves to hands and feet. Treat w/ vitamin B1.

Steps in formation of beta amyloid plaque

as it is being made, APP sticks through membrane. Enzymes cleave beta-amyloid protein, releasing it into the space outside the neuron. Clumps of beta-amyloid collect and begin to form a plaque.

Baptists vs Taoists

baptists beta amyloid, do research, get grants. Taoists quiet, neuroscience, more clinically, why aren't we looking at tao, neurofiblular tangles.

Top five ways to shorten life in order

be overweight, drink and drive, not eatin fruits and vegetables, be sedentary, smoking.

Psychosocial treatments

behavioral methods to reduce problematic behaviors and maintain independence. Memory aids, structure daily activities, envionrmental control, don't quiz; do rely on past. Education - routine, guilt, take precautions, ask for help. REDUCE CAREGIVER BURDEN.

Decorticate posturing

brain damaging. Tua football player injury. Had minor concussion 5 days prior too.

Genetic theoyr alzheimers

certain families more prone for early onset alzheimers. Study DNA. Lots of genes potential for increasing likelihood.

Tau in Alzheimers

changes chemically, loses ability to separate and support microtubules. Wind around each other. May eventually lead to death of neuron.

Down's Syndrome and Alzheimers

chromosome 21, also in Alzheimer's, if people with Down's syndrome live long enough then they will get Alzheimer's.

ApoE Abnormalities

chromosome19. Vulnerability. ApoE binds to beta amyloid and may lead to plaques. Three allelic variations (E2, E3 (most common), E4). E2E2 might even protect, manage lipids in effective way, not much beta amyloid. E4 alleles most interested in.

Older adults depression

cognitive changes mimicking alzheimers. Confusion, distraction, irritable outbursts. Also may be in conjunction with dementia. Treatable.

Dementia

common speech to refer to loss of cog abilities. Interferes with normal activities. Not a disease, just a descriptive term.

Issue with amyloid hypothesis

decades of research, gotten us like nowhere. Too many mouse models, too much research on amyloid.

Highly educated after diagnosis

decline much faster. Because have to be 1.5 sd below average to be diagnosed, so just happen to be further in disease before diagnosed.

Caregiver burden

describes stress that caregivers experience in daily management of afflicted relative . Higher rates of depression, stress, and isolation for caregivers.

Risks for Alzheimers

family history of dementia, down's syndrom, Parkinsons, mother > 40, head trauma with loss of consciousness, history of depression. NSAID or statin is reduced risk- must be inflammatory process.

Mild cognitive impairment (MCI)

form of neurocognitive disorder signifies individual may be at risk for developing Alzheimers.

Amyloid Precursor Protein

forms beta amyloid. Found naturally in brain. As manufactured, embeds in neurons membrane. Small part in, larger part outside.

Reversible neurocognitive disorders

from presence of medical condition that affects but doesn't destroy brain tissue. If medical condition not treated, permanetn damage maybe.

NINCDS-ADRDA Criteria

gold standard for diagnosing Alzheimers. National institute... Criteria based on medical and neuropsychological screening ttests, behavioral ratings, and mental status measures. 85-90% accurate in later stages.

Psychological symptoms of Alzheimer's

gradually over time. Early, occasional loss of memory for recent events or familiar tasks. Changes in personality and behaviour eventually evident. Most advanced, lose ability to perform simplest functions. Rate of progression varies, usually 4.2(m)-5.7(w) years survive after diagnosis.

Diagnosis of Alzheimer's

hard to diagnose. Majority that we used to call Alzheimer's are actually mixed dementia. Definitive Alzheimer's can't be diagnosed until after death. Up until that, can only have probable or possible Alzheimer's. Also biomarkers (cerebrospinal fluid, MRI) but usually just for research.

Subdural haematoma

head injury cause. Blood clot that creates pressure on brain tissue. Surgical intervention can releive.

Korsakoff syndrome

if WErnickes disease not treated. Chronic form.

Other genes modifying risk of E4

klvs clotho modifier, erase downside of ApoE4. Expensive and hard to get tested.

Big pharma alzheimers

lose a fortune of money. Can do it in a mouse but when go to humans, it doesn't work.

Neurocognitive disorder

loss of cognitive function severe enough to interfere with normal daily activities and social relationships.

Neurofibrillary tangles

made of tau proteins. Tau maintains microtubules within axons. Tangles form when tau changes chemically and can no longer support the microtubules. Leads to collapse of transport system within neuron. Malfunctions in communication between neurons, neuronal death. CLose correlation between tau in brain and amount of cognitive correlation.

Amnesia

main symptom is profound memory loss. May be unable to remember info after damage (anterograde) or prior to damage (retrograde). Caused by chronic substance use, medications, toxins, trauma to head, loss of oxygen, std.

Multifactorial Threshold model

many common alleles with 'low' penetrance. Most people will have several risk alleles. They are additive (multiplicative). Many additive environmental factors. Genes and environment → liability. Once liability reaches a certain value (threshold) a disease process begins.

Neurological impact of COVID

may cause bump in dementia because increased brain atrophy in some individuals.

Aricept and Ebixa

moderate to advanced alzheimers. Block glutamate from interacting with NMDA receptors, reduce toxicity of excess glutamate.

Presenilin Genes

most familial cases. PS1 chromosome 14, defect then mean age of onset 45, 50-80% early onset. PS2 defect chromosome 1, mean onset 52. Autosomal dominant transmission, if defect WILL get it. Columbian family. Leads APP to increase its productino of beta-amyloid.

Parkinsons disease

motor disturbances, tremors, speech impediments, slowing of movement, muscular rigidity, shuffling gait, postural instability. Neurocognitive during later stages. SOme alzheimers get parkinsons symptoms. Survive 10-15 years after symptoms.

Alzheimer's disease

neurocognitive disorder. Suffers from progressive and irreversible neuronal death. One type of dementia.

Aducanumab

new drug for Alzheimer's. Acetylcholinesterase inhibitor. Currently approved in US. INjection every 4 weeks, MRI to watch out for hemoraghing. 56,000$ a year. Canada says don't recommend approval.

Treatment parkinsons

no cure. Medications treat symptoms. Levodopa (over years loses effect). High frequency deep brain stimulation of subcortical movement areas.

Apolipoprotein E gene

one of prime genes thought to be involvedin late onset familial pattern. Chromosome 19. ApoE.

Onset & Course of Alzheimer's

onset early (40-65) or late 66+. ONset mild, course is steady deterioration. Body gradually sinks into coma and death.

Diagnosis of Neurocognitive disorder symptoms

process of exclusion. Amnesia: unwinds in time. Memory from recent events go first. Aphasia: loss of language ability. Misnaming, getting in wrong class. Apraxia: loss of ability to carry out coordinated movement. Like putting coat on toddler. Agnosia: loss of ability to recognize familiar objects.

Chronic traumatic encephalopathy

progressive degenerative neurological process found in some athletes who sustain multiple conclusions and sub-concussive blows. Characterized by cerebral atrophy and increased levels of tau protein, as well as dementia and, in some cases, depression. Evidence as early as 18.

Vascular neurocognitive disorder

progressively lose cognitive functioning as result of damage to arteries supplying brain. Multi-infarct dementia: most common form of vascular neurocog disorder. Caused by transient ischemic attacks. Number of minor strokes occur in which a clogged or burst artery interrupts blood flow to brain. Over time, progressive damage.

ApoE

protein that carries cholesterol through body, and binds to beta-amyloid, possibly play role in plaque formation.

Normal-pressure hydrocephalus

rare. Cognitive impairment, dementia, urinary incontincence, difficulty walking. Obstruction in flow of cerebrospinal fluid, accumumlates in brain. Early treatment divert fluid away.

Dementia rates in Europe and US

rates falling. Maybe because of less smoking, cardiovascular disease, cerebrovascular disease. However, subsequent generations have higher obesity and diabetes so will raise again.

Treatment alzheimers

really try to delay onset. Measures based on clinical judgement and cognitive perofrmance, instead of mortality. Anticholinesterases: decreases cholinesterases, allow more acetylcholine remain in brain. Memantine: block glutamate receptors, which reduces neuronal death. Temporarily provide modest relief for symptoms (memory/behavioral problems), do not treat underlying causes, only modestly effective at best, side effects of GI, nausea, vomitting. Countries start to pull out and not want to pay.

Pick's disease

relatively rare. Severe atrophy of frontal and temporal lobes. DIstinct from frontaltemporal because also accumulates unusual protein deposits (pick bodies). Symptoms disorientation an dmemory loss in early stages, eventually to pronounced personality changes, loss of social constraints. Eventually mute, immobile, incontinent.

Neurocognitive disorder w/ lewy bodies

similar to alzheimers in sumptoms. Fluctuate in severity, at least early on. Also confusion and hallucinations.

Second impact syndrome

still some swelling from first concussion, then when get more there is nowhere for the brain swelling to go, it goes into spinal column and can kill you.

Lewy bodies

tiny spherical structures consisting of deposits of protein found in dying nerve cels in damaged regions deep within brains of people with parkisnons.

Nun study

track nuns across lifespan, look at writings from beginning, then look at brains at death. Could tell even in 20s and 30s, in early writings, could predict who develop alzheimers. Chart life of Alzheimer's.

Issues with Alzheimer's Prevalence Rates

vary widely. Some have other cognitive disorders. Some include all some just alzeimers. Etc. There are other factors interfering. Educational influences.

Diagnosis of neurocognitive disorder

when signficant and progressive cognitive decline in one or more areas including social cognition, memory, aphasia (loss of planguage ability), apraxia (can't carry out coordinated movements), agnosia (loss of ability to recognize familiar objects), and disturbance in executive functioning. Process of exclusion. ONly autopsy reveal for sure.

Cognitive reserve

why can some brains get pathology but not show symptoms? Overall breain size, regional brain size, dendritic branching, neuyronal integrity, neuronal efficiency, adaptability, education, intelligence?? More to lose before symptoms emerge. None provide definitive measure, but all potentially useful.

Death once diagnosed

within 15 years, it's terminal