M9 - Cognition, Dementia, and Implications for Physical Activty

cognitive function

mental processes that allow us to

• think

• learn

• utilize language

• reason

• attention and concentration

• visiospatial functioning

cognitive decline

reduction or deterioration in cognitive functions

• naturally occurs w/ age

• rapid decline in later age (>70)

  • evidence unclear as to what age decline begins (20, 30, 50, 60?)

age and disease

age is a risk factor / associated w/ other age-related conditions

• CVD

• poor mental health

• low levels of PA

• hypercholesterolemia

crystallized intelligence

accumulated knowledge across one’s lifespan (knowledge, facts, verbal skills)

• reflects long-term memory

fluid intelligence

ability to reason, solve new problems, think abstractly without relying on prior knowledge (executive function, processing speed, psychomotor ability…)

• reflects processing speed and working memory

Harada CN et al 2013

found that normal cognitive aging (natural decline) does not result in inability to perform ADLs

• however, some may find complex cognitive tasks (e.g. driving) to be impaired

  • reductions in visual and attentional processing, visual perception, executive function, episodic and working memory

cognitive aging variability

There is large individual variability in the degree of cognitive change with age — not everyone experiences the same rate or pattern of decline.

• Contributing factors to cognitive aging include:

  • Genetics (~60%) — strong heritable influence on cognitive performance.

  • Medical conditions — e.g., cardiovascular disease, diabetes, hypertension.

  • Sensory deficits — such as hearing or vision loss, which can indirectly impair cognition.

  • Lifestyle factors — physical activity, diet, social engagement, education, and mental stimulation all play protective roles.

activities associated with higher cognitive function

activities associated with higher cognitive function in older adults

1. Intellectually engaging activities

• puzzles, reading, using computer, board games, musical instruments

2. Physical activities

• exercise, especially ones that improve CV health

• gardening, dancing

3. Social engagement

• travel, cultural events

• socializing w/ friends and family

cognitive retraining

mental exercises and strategies designed to improve or maintain specific cognitive skills

• e.g. strategies to improve memory, reasoning, speed of processing

Willis et al 2006

found that cognitive retraining in healthy older subjects resulted in improvements on cognitive tests and carrying out ADLs

• effects can last for years and show that mental abilities can be strengthened through practice, even in later life

cognitive impairment

general term describing any measurable decline in one or more cognitive functions (memory, attention, language, reasoning, etc.) that is greater than normal aging, but may or may not interfere with daily life

• impairs memory, language, thinking, judgement

• exists on a continuum ranging from mild to severe

pathological neurodegeneration

progressive damage to brain cells and neural connections

dementia

type of cognitive impairment that is severe, chronic, and progressive

• caused by pathological neurodegeneration

dementia types

different types

• Alzheimer’s disease (AD)

• Vascular dementia (VaD)

• Dementia with Lew bodies (DLB)

• Frontotemporal dementia (FTD)

AD

Pathology: Accumulation of β-amyloid plaques (outside neurons) and neurofibrillary tangles (inside neurons).

• Primary cognitive effects: Impaired learning and memory, followed by deficits in executive function and language.

• Progression: Gradual and progressive decline over years.

beta amyloid plaques

clumps of protein fragments that build up outside neurons (in the spaces between brain cells).

• they disrupt communication between neurons and trigger inflammation, which can damage surrounding brain tissue

neurofibrillary tangles

twisted fibers of a protein called tau that accumulate inside neurons.

• Normally, tau helps stabilize microtubules (part of the neuron’s internal “skeleton” for transporting nutrients and signals).

• In Alzheimer’s, tau becomes abnormal and forms tangles, disrupting transport within the neuron, eventually leading to cell death

VaD

Results from vascular disease, such as strokes, small vessel disease, or reduced blood flow to the brain.

• Pathology: Infarcts or damage to brain tissue due to impaired circulation.

• Symptoms: Highly variable, depending on the region affected; often includes executive function deficits (e.g., planning, organizing).

• Progression: Often stepwise, worsening after each vascular event.

DLB

Pathology: Presence of Lewy bodies — abnormal clumps of α-synuclein protein within neurons.

• Cognitive profile: Similar impairments to Alzheimer’s (memory, executive function) but with:

  • Visual hallucinations

  • Visuospatial impairment

  • Fluctuating alertness or attention

  • Often co-occurs with Parkinsonian motor symptoms (rigidity, slow movement).

FTD

Pathology: Degeneration in frontal and temporal lobes of the brain.

• Cognitive effects: Prominent changes in language and executive function; memory may remain relatively preserved early on.

• Symptoms:

  • Behavioural variant: Personality changes, disinhibition, apathy.

  • Language variants: Difficulty speaking or understanding language (primary progressive aphasia).

mini mental state exam

screening tool used to assess cognitive function, often in older adults, in both clinical and research settings

Contains 11 questions assessing:

• Orientation (e.g., date, location)

• Attention and concentration (e.g., counting backwards)

• Memory (e.g., recalling words)

• Language (e.g., naming objects, following commands)

• Visuospatial skills (some tasks may include drawing)

provides a snapshot of cognitive function

can be used to track changes over time (e.g., disease progression or response to treatment)

MMSE scoring

Maximum score: 30 points

• Cut-off for cognitive impairment: <24 points

MMSE caveat

MMSE is not diagnostic on its own — it only flags possible cognitive impairment.

• Performance can be influenced by education, language, or cultural factors, so scores should be interpreted carefully.

Fratiglioni et al. 2004

Purpose: Examine whether lifestyle factors in late life — specifically physical activity, social integration and mental/mental‐leisure activities — are associated with reduced risk of cognitive decline and dementia

Goal: Determine if an “active and socially integrated lifestyle” could serve as a protective factor against the development of dementia (including Alzheimer’s Disease) by exploring published longitudinal studies and assessing biological plausibility

Fratiglioni et al methods

• Design: A systematic review of longitudinal epidemiological studies examining the relationship between lifestyle (physical, social, and mental activities) and cognitive outcomes/dementia

• Population: Older adults (aged 60+ in many studies) drawn from existing longitudinal datasets. (The review draws on multiple studies rather than a single cohort)

• Key variables:

  • Exposure: Physical leisure activities, social network / social integration, non‐physical leisure (mental/ cognitive) activities.

  • Outcome: Cognitive impairment, dementia incidence (including Alzheimer’s disease)

• Hypotheses: The review considered three major etiological hypotheses through which lifestyle may influence dementia risk: the cognitive reserve hypothesis, the vascular hypothesis, and the stress hypothesis

Fratiglioni et al findings

evidence across multiple longitudinal studies suggest better cognitive outcomes and lower risk of dementia associated with

• higher levels of PA, stronger social networks, greater mental/leisure activity participation in late life

  • although associations are strong, causality cannot be fully established given observational design and potential for reverse causation (e.g., people with early cognitive decline may reduce activity)

cognitive reserve hypothesis

some people’s brains can better tolerate damage or pathology (like Alzheimer’s plaques or tangles) without showing clinical symptoms

• cognitive reserve is built through lifelong learning, mentally stimulating activities, and complex occupational or leisure engagement.

• It may involve:

  • More efficient brain networks (neurons communicate more effectively)

  • Alternative neural pathways (the brain can “reroute” around damaged areas)

PA increases non-neural components of brain, mental stimulation, increases synaptogenesis

vascular hypothesis

Cardiovascular health directly affects brain health, and vascular disease can contribute to cognitive decline and dementia.

• Mechanism:

  • Physical inactivity, hypertension, diabetes, and obesity increase risk of strokes, micro-infarcts, and poor blood flow to the brain.

  • Brain regions that receive less blood are more prone to cell death and cognitive impairment

PA reduces risk of CVD which is associated with VaD

stress hypothesis

• Chronic psychological stress and related factors (like depression) negatively affect brain function and structure, contributing to cognitive decline.

• Mechanism:

  • Stress increases cortisol and other stress hormones, which can damage the hippocampus (key area for memory) and impair cognitive function.

  • Chronic stress can also reduce neurogenesis (growth of new neurons) and synaptic plasticity

PA can act as a stress reducer

hypotheses examples

CRH

• two people may have the same amount of brain pathology, but the one with higher cognitive reserve might show fewer cognitive symptoms

VH

• someone with uncontrolled hypertension may have small strokes or white matter lesions, increasing their risk of vascular dementia

SH

• lder adults who are socially isolated, anxious, or depressed may show faster cognitive decline

scaffolding theory of aging and cognition

as the brain ages, some neural structures decline (e.g., loss of neurons, synapses, and white matter integrity).

• to compensate, the brain recruits alternative neural circuits or networks — this is called “scaffolding.”

• scaffolding helps maintain cognitive performance even when the original pathways are weakened

PA and MCI

PA/exercise can improve cognitive function in individuals with MCI

• includes aerobic, resistance, flexibility PA/exercise

PA and other benefits

PA/exercise also positively affects conditions often associated with aging:

• Reduces risk of depression

• Improves metabolic health (reduces risk of diabetes, hypertension)

• Supports musculoskeletal health (reduces osteoporosis risk)

• Reduces overall mortality risk

Kumar et al 2022

Purpose: Investigate the association between frequent vigorous physical activity (PA) and cognitive functioning in older adults (aged 60+) in India, controlling for individual, health, lifestyle, and household factors. PMC+1

Goal: Determine whether older Indian adults who engage in frequent vigorous PA exhibit better cognitive functioning compared to those who do not, and whether there are gender differences in this relationship

Kumar et al methods

Design & Data: Cross-sectional analysis of 31,464 Indian adults aged 60+ from the Longitudinal Ageing Study in India (LASI, 2017–2018).

Exposure (PA): Daily vigorous physical activity (e.g., running, swimming, fast bicycling, heavy farm work) vs. less frequent activity.

• (yes freq. vigorous PA vs no, not every day)

Outcome: Cognitive function measured with a composite score (0–43) across memory, orientation, arithmetic, executive function, and object naming.

Analysis: Propensity score matching to compare active vs. less active participants, estimating the effect of frequent PA on cognitive function.

propensity score matching

for each person who does daily vigorous PA, find a “match” among less active people who have similar characteristics (age, sex, education, health, etc.)

• creates comparable groups, making it more likely that differences in cognitive scores are due to PA itself rather than other factors

Kumar et al results

Prevalence: ~25% of men and ~12% of women engaged in daily vigorous PA.

Cognitive scores: Frequently active adults had higher cognitive scores than less active peers:

• Men: +0.73 (unmatched) / +0.98 (matched PSM)

• Women: +1.07 (unmatched) / +1.32 (matched PSM)

Key points: Association remained significant after adjusting for covariates; effect was slightly stronger in women.

Kumar et al discussion

Interpretation: Frequent vigorous physical activity supports cognitive health in older Indian adults, consistent with findings from other countries.

Possible mechanisms: PA may improve cardiovascular health, promote brain structure/function (neurogenesis, synaptic plasticity), and enhance cognitive reserve.

Limitations: Cross-sectional design prevents causal inference; self-reported PA may be biased; “vigorous” PA includes heavy farm work, which may differ from other contexts.

Implications: PA is a modifiable factor that could be promoted to support cognitive aging, particularly in women; further longitudinal studies and interventions are needed.

Quigley et al 2000

Purpose: To review existing evidence on how physical activity and structured exercise affect cognitive performance in older adults, and to identify underlying biological mechanisms and exercise‐prescription recommendations.
Goal: Provide a resource for researchers and practitioners (especially in kinesiology, physiotherapy and gerontology) on how to design exercise interventions for older adults to support cognition.

Quigley et al methods

Design: Narrative (non‐systematic) review of published literature relating exercise to cognitive outcomes in older adults (without necessarily cognitive impairment)

Focus areas: Types of exercise (aerobic, resistance, flexibility), intensity/duration/frequency, target cognitive domains (memory, executive function, processing speed), and how physiological mechanisms may mediate effects (e.g., neuroplasticity, vascular health, inflammation, HPA axis).

HPA axis modulation

HPA stands for Hypothalamic-Pituitary-Adrenal axis.

• A major stress-response system in the body:

  1. The hypothalamus (in the brain) detects stress and releases CRH (corticotropin-releasing hormone).

  2. CRH signals the pituitary gland to release ACTH (adrenocorticotropic hormone).

  3. ACTH signals the adrenal glands (on top of kidneys) to release cortisol, the “stress hormone”

• Chronic stress → high cortisol → can damage the hippocampus, impair memory, and affect other cognitive functions.

• Healthy HPA axis function → balanced cortisol → protects brain health

Quigley et al results

substantial evidence that exercise benefits cognitive performance in older adults, particularly in domains like attention, processing speed, executive function and memory

• They highlighted mechanisms through which exercise exerts cognitive benefits:

  • Up‐regulation of growth factors/neuroplasticity

  • Improved vascular function and circulation.

  • Reduced inflammation, improved metabolic control, and HPA axis modulation.

• They proposed preliminary exercise prescription parameters (e.g., frequency, type, intensity) though evidence regarding optimal “dose” remained incomplete

Quigley et al discussion

while exercise appears promising for cognitive health in aging, there are gaps: heterogeneity of studies (different types of exercise, populations, outcome measures), and limited data on specific “dose” or comparative modalities

• For practitioners in rehabilitation/kinesiology, they suggest integrating physical exercise (especially aerobic plus resistance) as part of interventions aimed at cognitive health in older adults.

• They caution that future research needs to better define mechanisms, intensity/duration recommendations, and target older adults across the spectrum (healthy aging, MCI, dementia risk).

Quigley et al figure 1

potential biological mechanisms underlying cognitive gains w/ PA

• PA (aerobic, resistance, combined aerobic + resistance, mind-body)

  1. inc growth factors (BDNF, VEGF, IGF) → inc neuroplasticity

  2. dec inflammation (CRP, IL-6, other cytokines)

  3. inc CV and cerebrovascular health → inc cerebrovascular reserve, glucose and O₂ transport to brain, cerebral blood flow

  4. dec HPA axis → dec stress hormones → dec stress response

• Improved cognitive performance

  • inc attention, processing speed, executive function, memory