Dementia Overview and Pathophysiology
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Questions and Answers

What is the observed effect of consuming over 21 units of alcohol per week on dementia risk?

  • It reduces the risk of dementia-related memory decline.
  • It has no impact on dementia risk.
  • It is linked to a 10% decrease in dementia risk.
  • It is associated with a 17% increase in dementia risk. (correct)

Which factor has been linked to a decrease in the risk of dementia for smokers?

  • Increased exposure to second-hand smoke
  • Ceasing smoking, even in later years (correct)
  • Maintaining a consistent smoking habit
  • Switching to vaping alternatives

How does social isolation specifically affect the risk of developing dementia?

  • Isolation decreases cognitive reserves.
  • It has no relation to dementia risk.
  • It increases social interaction opportunities.
  • Reduced social contact raises the risk of dementia. (correct)

What role does obesity play in the risk of dementia?

<p>Higher BMI is connected to an increased risk of developing dementia. (A)</p> Signup and view all the answers

What implication does physical inactivity have in the context of dementia?

<p>It can be both a consequence and a contributing factor of dementia. (A)</p> Signup and view all the answers

How does depression relate to the onset of dementia?

<p>Early depressive symptoms may emerge from neurodegenerative changes. (A)</p> Signup and view all the answers

What is a key pathological feature of Alzheimer's disease?

<p>Accumulation of proteins such as β-amyloid and tau (D)</p> Signup and view all the answers

What impact does air pollution have in relation to dementia?

<p>Airborne pollutants expedite neurodegenerative processes. (D)</p> Signup and view all the answers

Which demographic is most affected by Alzheimer's disease?

<p>Women aged 85 and above (D)</p> Signup and view all the answers

What is suggested about the relationship between diabetes and dementia?

<p>Type 2 diabetes poses a distinct risk for the onset of dementia. (C)</p> Signup and view all the answers

What kind of dementia syndrome is typically associated with adult forms of leukodystrophy?

<p>Subcortical dementia syndrome (A)</p> Signup and view all the answers

What is the primary cellular dysfunction in neurodegenerative diseases?

<p>Disruption of proteostasis (B)</p> Signup and view all the answers

What is the primary consequence of protein aggregation in neurodegenerative diseases?

<p>Obstruction of axons and dendrites (C)</p> Signup and view all the answers

What morphological changes occur in the brains of individuals with Alzheimer's disease?

<p>Narrowing of gyri and widening of sulci (A)</p> Signup and view all the answers

Which condition is NOT typically associated with extensive white matter lesions?

<p>Creutzfeldt-Jakob disease (C)</p> Signup and view all the answers

What primarily characterizes the clinical progression of Alzheimer's disease?

<p>Gradual and progressive memory loss (A)</p> Signup and view all the answers

What characterizes Lewy bodies in terms of structural composition?

<p>Straight neurofilaments measuring 7–20 nm, surrounded by amorphous material. (D)</p> Signup and view all the answers

Which areas of the brain are primarily affected in Lewy Body Dementia?

<p>Substantia nigra, amygdala, cingulate gyrus, and neocortex. (D)</p> Signup and view all the answers

What are the three progressive stages of Lewy Body Disease, according to formal criteria?

<p>Brainstem predominant, transitional limbic, diffuse neocortical. (B)</p> Signup and view all the answers

Which feature is NOT commonly associated with the presentation of Parkinson’s disease as it relates to Lewy Body Dementia?

<p>Visual hallucinations as a primary symptom. (D)</p> Signup and view all the answers

What is a prominent neurochemical deficit observed in most patients with Dementia with Lewy Bodies?

<p>Cholinergic deficit linked to the basal forebrain. (B)</p> Signup and view all the answers

How does cognitive decline in Lewy Body Disease compare to that in classic Parkinson's disease?

<p>It extends to daily living activities, affecting more than typical PD symptoms. (D)</p> Signup and view all the answers

What primary diagnostic criteria are associated with Dementia with Lewy Bodies?

<p>Marked fluctuations in cognition and well-formed visual hallucinations. (D)</p> Signup and view all the answers

In the context of Lewy Body Demetia, which cognitive deficits are typically observed?

<p>Executive, attentional, and visuospatial deficits. (B)</p> Signup and view all the answers

Which symptom is NOT commonly associated with individuals suffering from a behavioral variant disorder?

<p>Hyperactivity (C)</p> Signup and view all the answers

What characterizes the primary progressive aphasia semantic variant?

<p>Decline in comprehension of meanings (C)</p> Signup and view all the answers

Which of the following statements about Lewy Body Dementia (LBD) is incorrect?

<p>It is associated with numerous neurofibrillary tangles. (D)</p> Signup and view all the answers

Which factor is NOT believed to contribute to the development of Lewy Body Dementia (LBD)?

<p>Lifestyle choices (A)</p> Signup and view all the answers

Which feature differentiates Pick disease from Alzheimer's disease?

<p>Onset in mid-adult life (A)</p> Signup and view all the answers

Individuals with which variant of primary progressive aphasia have noticeable motor speech impairment?

<p>Nonfluent/agrammatic variant (D)</p> Signup and view all the answers

What is the typical progression timeline for symptomatic sporadic Pick disease?

<p>Consistently within 3-10 years (D)</p> Signup and view all the answers

What is a common behavioral symptom associated with Lewy Body Dementia?

<p>Visual hallucinations (B)</p> Signup and view all the answers

What characterizes arteriolosclerosis?

<p>Thickening of arterioles due to plasma protein infiltration (C)</p> Signup and view all the answers

Which statement accurately reflects the consequences of concurrent cerebrovascular and neurodegenerative lesions?

<p>The resulting cognitive and functional decline exceeds expectations based on each disease mechanism separately. (D)</p> Signup and view all the answers

Which of the following contributes significantly to brain atrophy in the elderly?

<p>Sensorineural hearing loss (C)</p> Signup and view all the answers

What role may the blood-brain barrier play in dementia when cerebrovascular and neurodegenerative processes coincide?

<p>It may allow neurotoxic or inflammatory agents to infiltrate the brain. (B)</p> Signup and view all the answers

In the context of hearing impairment, how is cognitive decline measured according to the study mentioned?

<p>With a 10 dB increase in hearing loss as a baseline (C)</p> Signup and view all the answers

What is a feature of cerebral amyloid angiopathy?

<p>Deposition of β-amyloid in the walls of small cerebral vessels (C)</p> Signup and view all the answers

How do cerebrovascular diseases impact the clearance of pathogenic molecules in the brain?

<p>They disrupt perivascular drainage pathways, impairing clearance. (B)</p> Signup and view all the answers

What is the relationship between hearing loss and cognitive decline in elderly populations?

<p>Cognitive decline occurs with both clinical and subclinical levels of hearing impairment. (D)</p> Signup and view all the answers

What aspect of hearing impairment significantly impacts cognitive processes such as working memory?

<p>Elevated cognitive load due to processing difficulties (C)</p> Signup and view all the answers

Which brain structures are notably impacted by chronic hearing impairment?

<p>Frontal lobe and hippocampus (B)</p> Signup and view all the answers

How can social disengagement due to hearing loss affect cognitive health?

<p>It may trigger negative biological mechanisms. (B)</p> Signup and view all the answers

What is a shared neurodegenerative process observed in both hearing loss and cognitive impairment?

<p>Degeneration of the stria vascularis and alterations in neurotransmitter release (A)</p> Signup and view all the answers

Which condition is linked to prolonged neurodegenerative processes resembling Alzheimer's disease following trauma?

<p>Mild recurrent traumatic brain injury (TBI) (D)</p> Signup and view all the answers

What contributes significantly to the onset of dementia following traumatic brain injury (TBI)?

<p>Cerebrovascular dysfunction (CVD) (C)</p> Signup and view all the answers

What common effect does hearing loss have on communication that can lead to cognitive disorders?

<p>Challenges in effective communication (B)</p> Signup and view all the answers

What is a potential biological consequence of social isolation resulting from hearing impairment?

<p>Increased transcription of pro-inflammatory genes (C)</p> Signup and view all the answers

Flashcards

Prion diseases

Neurodegenerative diseases causing widespread neuronal loss, gliosis, and spongiform changes, leading to cognitive dysfunction.

Leukodystrophy

Neurological disorders characterized by subcortical dementia, with symptoms focused in the frontal lobes.

Protein aggregation

The clumping of proteins, hindering cell function and homeostasis.

Proteostasis

The cellular process that maintains protein balance.

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Alzheimer's Disease (AD)

Most common form of dementia, marked by amyloid and tau protein buildup, and characterized by progressing memory loss and cognitive decline.

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Cortical atrophy

Loss of brain matter in the outer layer of the brain.

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β-amyloid and tau

Abnormal proteins that accumulate in the brain in Alzheimer's disease, contributing to the disease's pathology.

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Hydrocephalus ex vacuo

Brain swelling due to shrinking of brain tissue (cortical atrophy) in the absence of excess fluid or disease.

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Alcohol Consumption and Dementia Risk

High alcohol consumption (over 21 units per week) and prolonged abstinence are linked to a 17% increased risk of dementia compared to moderate drinking.

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Obesity and Dementia

Higher Body Mass Index (BMI) is strongly associated with a greater risk of dementia.

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Smoking and Dementia Risk

Quitting smoking, even later in life, reduces dementia risk. Exposure to secondhand smoke increases memory decline, especially with longer exposure.

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Depression and Dementia

Depression can be a symptom of early-stage dementia, or conversely, dementia can cause depression.

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Social Isolation and Dementia

Social isolation raises the risk of dementia. Social interaction protects against dementia.

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Physical Inactivity and Dementia

Lack of exercise can be both a result and a cause of dementia, especially in those with cardiovascular issues.

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Air Pollution and Dementia

Air pollutants speed up neurodegenerative processes by affecting the circulatory system and brain tissue, possibly exacerbating dementia.

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Diabetes and Dementia Risk

Type 2 diabetes increases the risk of dementia.

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Behavioral Variant of FTD

A type of frontotemporal dementia characterized by personality and behavioral changes, including apathy, disinhibition, and impaired judgment.

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Semantic Variant PPA

A type of primary progressive aphasia causing difficulty understanding the meaning of words, objects, people, and emotions.

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Nonfluent/agrammatic PPA

A type of primary progressive aphasia marked by difficulty in generating words, potentially with motor speech impairment.

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Lewy Body Dementia (LBD)

A neurodegenerative disease characterized by Lewy bodies (alpha-synuclein aggregates) in cortical neurons, causing dementia, often with parkinsonian symptoms.

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Pick Disease

A frontotemporal dementia (FTLD) type clinically manifesting with primary syndromes like behavioral variant, semantic variant PPA, and nonfluent/agrammatic variant PPA.

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Parkinson's Disease Dementia (PDD)

Parkinson's disease that progresses to include dementia, a symptom of Lewy Body Dementia.

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Dementia with Lewy Bodies (DLB)

A Lewy body dementia form characterized by dementia, but without prominent early Parkinsonian symptoms

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Frontotemporal Dementia (FTD)

A group of neurodegenerative disorders, primarily affecting the frontal and temporal lobes, and often categorized into Behavioral Variant, Semantic Variant, and Nonfluent/agrammatic PPA.

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Arteriolosclerosis

Thickening of small arteries due to infiltration of plasma proteins into the vessel wall.

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Cerebral Amyloid Angiopathy

Accumulation of β-amyloid peptide in the walls of small brain arteries, causing damage to their structure.

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Synergy of Brain Pathologies

When both cerebrovascular and neurodegenerative diseases affect the brain, the resulting cognitive decline is worse than the sum of their individual effects.

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Blood-Brain Barrier Compromise

Damage to the protective barrier between blood and brain allows neurotoxic substances to enter, potentially worsening cognitive decline.

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β-Amyloid Clearance Disruption

Brain's ability to remove harmful β-amyloid is hindered, potentially due to impaired vascular motion, contributing to cognitive decline.

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Sensorineural Hearing Loss (SNHL)

Age-related decline in hearing caused by damage to the inner ear or auditory nerve.

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SNHL and Cognitive Decline

Hearing loss is linked to cognitive decline, even at subclinical levels.

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Brain Atrophy Connection

Cognitive decline, MCI, AD, and hearing loss all contribute to brain shrinking.

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Lewy Body Dementia

A neurodegenerative disease characterized by the presence of Lewy bodies, protein deposits found in brain cells, affecting cognitive function, movement, and behavior.

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Lewy Body

A microscopic cluster of protein (mostly alpha-synuclein) found within brain cells, often associated with Lewy Body Dementia and Parkinson's disease.

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Alpha-Synuclein

A protein that, when misfolded and aggregated, contributes to the formation of Lewy bodies, a key feature of Lewy Body Dementia.

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Stages of Lewy Body Dementia

Lewy Body Dementia progresses through 3 stages: 1) Brainstem predominant, 2) Transitional limbic, and 3) Diffuse neocortical, affecting different brain regions.

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PDD (Parkinson's Disease Dementia)

A type of Lewy body dementia where cognitive decline occurs later, after motor symptoms like tremors and slow movements.

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DLB (Dementia with Lewy Bodies)

A type of Lewy Body dementia where cognitive decline is prominent and evident earlier, accompanied by visual hallucinations, sleep disturbances, and other behavioral symptoms.

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Cholinergic Deficit

A deficiency of acetylcholine, a neurotransmitter essential for memory and cognitive function, common in Lewy Body Dementia.

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Fluctuating Cognition

A characteristic feature of Lewy Body Dementia where mental abilities can change rapidly and significantly over short periods.

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Cognitive Load and Hearing Loss

Hearing loss increases the brain's effort to process speech, leading to possible structural changes and neurodegeneration. This may impact other cognitive areas like working memory.

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Brain Changes in Hearing Loss

Hearing loss is tied to a decrease in brain volume, especially in areas responsible for sound processing. Reduced activation of auditory pathways and atrophy of frontal lobe and hippocampus also occur.

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Shared Neurodegenerative Process

Both hearing loss and dementia can be traced back to a shared degeneration in the aging brain. This includes loss of hair cells, neurons, and changes in neurotransmitter function.

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Social Isolation and Hearing Loss

Communication difficulties from hearing loss can lead to social withdrawal, a risk factor for dementia. Reduced social stimulation and increased inflammation contribute to this link.

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TBI and Dementia Connection

Severe traumatic brain injury, especially repeated mild injuries, can trigger prolonged neurodegenerative processes, potentially leading to dementia.

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Cerebrovascular Dysfunction and TBI

Cerebrovascular dysfunction (CVD) plays a crucial role in the development of dementia following TBI. This highlights the connection between blood flow problems and brain degeneration.

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Post-traumatic Dementia

While TBI often leads to neurodegeneration, specifically pinpointing types of dementia in clinical practice remains a challenge.

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TBI and Alzheimer's

Neurodegeneration following TBI can resemble features of Alzheimer's Disease, suggesting a possible connection between TBI and this specific type of dementia.

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Study Notes

Dementia Overview

  • Dementia is a decline in cognitive ability over time, hindering daily activities. Memory loss is often the initial symptom.
  • Dementia involves significant cognitive impairment, impacting routine tasks.
  • Cellular inclusions and extracellular protein accumulation are common features, accompanied by glial and microglial activation.

Learning Outcomes

  • Students will review pathophysiology and risk factors of dementia (Alzheimer's, Vascular, Lewy Body, Frontotemporal, Parkinson's).
  • They will evaluate evidence on hearing impairment as a modifiable dementia risk.
  • A hypothesis for the pathophysiology of traumatic brain injury and its relationship to dementia will be developed.
  • The connection between gut microbiome and dementia pathophysiology will be critically evaluated.

Risk Factors

  • Early Life (under 45): Lower education levels impact cognitive reserve.
  • Midlife (45-65): Risk factors like hearing loss, hypertension, alcohol use, smoking, and social isolation contribute to cognitive reserve.
  • Later Life (over 65): Physical inactivity, diabetes, and air pollution further contribute to cognitive decline.

Dementia - Pathophysiology

  • Pathological anatomy: Dementias often have widespread, complex pathology making localization and quantification challenging.
  • Memory impairment: Extensive disease in brain areas crucial for memory (diencephalon, medial temporal lobes) is a key feature.
  • Language impairment: Damage to the dominant cerebral hemisphere (especially frontal, temporal, and parietal lobes) disrupts language function.
  • Reading and Calculation: Posterior part of the left cerebral hemisphere is essential for these tasks.
  • Executive Function: Frontal lobe degeneration impairs behavior modulation and stability of personality.
  • Lesions (general): Located in the convolutions (especially frontal and temporal poles), corpus callosum, and the thalamus.

Dementia - Pathophysiology of Degenerative Types

  • Clinical manifestation: Determined by the location and extent of the cerebral disease. The diencephalon and basal ganglia are sometimes implicated alongside the cerebral cortex.
  • Thalamic degenerations: Can affect memory, due to the integral connections with the cerebral cortex.
  • Alzheimer's Disease: ẞ-amyloid and tau protein accumulation are central. Initially, hippocampus, then the basal frontal cortex and memory decline increases significantly.

Dementia - Pathophysiology - Biochemistry of Proteins

  • Intracellular inclusions: Often deeply intertwined with neurodegenerative disorders, representing early histologic abnormalities.
  • Protein homeostasis: Disruption of normal protein homeostasis likely plays a central role in the progression of neurodegenerative disorders.
  • Compromised cellular proteins: Inclusions signify compromised native cellular proteins and their stress response conjugates.
  • Stress response activation: Cells activate stress responses to damage. The presence of stress responses doesn't pinpoint the cause of damage but rather the cellular response to it.

Dementia - Pathophysiology - Proteostasis

  • Proteostasis disorders: Disorders of protein synthesis, folding, trafficking, aggregation, disaggregation, and degradation are widely implicated in neurodegenerative diseases.
  • Toxic Fibrils: Aggregated proteins can form toxic fibrils, perpetuating and intensifying cellular stress.

Dementia Categories

  • Alzheimer's Disease (AD): Characterized by the accumulation of ß-amyloid and tau proteins, resulting in gradual and progressive cognitive decline, including memory loss.
    • Significant concern in the elderly (over 50%), with prevalence increasing above 85.
  • Frontotemporal Dementia (FTLD): Typically characterized by abnormal tau accumulation without ß-amyloid. The initial presentation often features disruptive and inappropriate behaviors.
  • Lewy Body Dementia (LBD): Includes Parkinson's Disease Dementia (PDD) or Dementia with Lewy Bodies (DLB) and demonstrates widespread cortical engagement with Lewy Bodies, lacking neurofibrillary tangles and amyloid plaques.
  • Vascular Dementia: A condition with cognitive decline related to multiple strokes or diminished blood flow.

Hearing Impairment & Dementia

  • Hearing impairment in the elderly is often age-related (sensorineural hearing loss) affecting auditory function and different ways dependent on the affected part of the pathway.
  • Hearing loss and subsequent cognitive decline is often associated with brain atrophy which includes structural changes, and a reduction in overall brain volume.
  • Cognitive load increases with hearing loss. Individuals need to exert more cognitive effort processing and understanding speech leading to relevant brain changes.
  • Social isolation may arise from communication challenges, impacting cognition and increasing pro-inflammatory markers.

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Description

This quiz explores the intricacies of dementia, focusing on its cognitive decline and various types such as Alzheimer's and Vascular dementia. Students will analyze risk factors, including the role of hearing impairment and gut microbiome in dementia pathophysiology. Prepare to deepen your understanding of how early and midlife factors contribute to cognitive impairment.

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