Physical and Cognitive Activity for Dementia

Dementia resulting from neurodegenerative conditions typically begins as subjective cognitive complaints of memory problems or difficulty thinking but with no objective evidence of impairment. This early stage of subjective cognitive complaints then progresses to mild cognitive impairment (MCI), in which there are objective measurable cognitive deficits with intact function for activities of daily living (ADL). In approximately 40% of people with MCI, dementia then develops, in which there is both objective cognitive decline and loss of function for ADL. We review growing evidence that physical activity alone or in combination with other interventions may protect cognition and prevent or less cognitive decline and loss of function.

Cognitive Resilience

Amyloid and tau imaging and autopsy-based neuropath-ology studies demonstrate that many individuals remain free of cognitive impairment despite the presence of mild protein-opathy. A wide range of lifestyle and psychologic indices are related to the level and rate of cognitive changes without a known relationship to brain pathology, including education; engagement in complex occupations; cognitive, social, and physical activities; and neuropsychiatric conditions. The complex interaction of environmental and lifestyle factors that contribute to cognition occur on a backdrop of person-specific genomic differences that, in turn, influence whether neurodegenerative processes leading to dementia will occur. This interplay of protective and detrimental processes leads to development of a dementia phenotype. As we search for agents that can measurably improve cognition or slow decline, the public health imperative is to delay onset of cognitive decline and disease. This raises the prospect of enriching lifestyle and environmental factors to delay cognitive impairment and dementia.

Early and Late-Life Enrichment

Late-life cognition is the culmination of positive and negative factors across the lifespan. Well known cardiovascular risk factors (eg, diabetes, hypertension, hypercholesterolemia, and smoking) increase the odds of developing dementia, in part because of their well-known effects on cerebrovascular and cardiovascular disease. These risk factors are closely linked with lifestyle factors, including physical activity, diet, and stress. A study of healthy lifestyle defined as nonsmoking, moderate-to-vigorous physical activity, light-to-moderate alcohol consumption, a Mediterranean or dietary-approaches-to-stop-hypertension (DASH) diet, and engagement in late-life cognitive activities revealed a lower risk of developing Alzheimer disease (AD) in 2 longitudinal cohorts of the Chicago Health and Aging Project as well as in the Rush Memory and Aging Project among people who did not have dementia at baseline.¹ A study evaluating cardiovascular risk burden, as measured by the Framingham General Risk burden, showed an association of higher cardiovascular risk burden with neurodegeneration, vascular lesions, and faster cognitive decline via effects on episodic and working memory as well as perceptual speed.²

Early-life cognitive enrichment has been found to increase chances of later-life cognitive health. Early-life high socioeconomic status, availability of cognitive resources from birth to age 12 years, frequency of participation in cognitively stimulating activities, and early-life foreign language instruction were associated with slower cognitive decline and lower global AD pathology burden.³ This is consistent with data from the Scottish Mental Survey.^4,5 In a study of 93 urban community-dwelling African Americans, early-life enrichment before age 13 years was associated with favorable outcomes in educational attainment, processing speed, and executive functioning.⁶

Physical Activity and Cognition in Adults

We searched the PubMed database for meta-analyses and systematic reviews using: physical activity, activity, exercise with normal cognition, subjective memory complaints, mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease dementia, Lewy body dementia, frontotemporal dementia, primary progressive aphasia, corticobasal ganglionic degeneration, progressive supranuclear palsy, and vascular dementia. The search retrieved 45 meta-analyses and systematic reviews (Table). Some retrieved studies, however, included heterogeneous populations (eg, combining MCI and AD or cognitively normal and MCI), and others had poorly defined populations (eg, cognitively impaired or unspecified dementia).

There is data to advocate physical, cognitive, social and multimodality interventions to reduce falls and caregiver burden and help improve cognition, function, gait, balance, and neuropsychiatric symptoms. Benefits can be seen as early as in normal cognitive state to advanced dementia for people living at home, in senior communities, or residential-care facilities.

Cognitively Healthy or At-Risk Individuals

As shown in the Table, 8 of 10 analytic reviews of the effects of activity on healthy people showed benefits.^7-16 Studies included physical exercise, cognitive and multimodal training. Improvements in overall cognition and specific cognitive domains were seen. Some analyses showed slowing of cognitive decline¹⁰ and protective effects against developing dementia.^13,15 Meta-analysis of biomarkers showed physical activity improved hippocampal and other brain region volumes,¹⁷ although another study showed no effect on brain volumes.¹⁸ Studies were inconclusive regarding effects on amyloid.¹⁹ There is consensus among studies that physical activity conveys cognitive benefits but no agreement that a specific activity is superior to others for cognition. In a Finnish randomized controlled trial, a multidomain lifestyle intervention among at-risk individuals age 60 to 77 prevented cognitive decline. In this 2-year study, 1,260 cognitively well but at-risk individuals were randomly assigned 1:1 to receive a multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring or general health advice. The primary endpoint was change in cognition measured at baseline and annually thereafter. After 2 years, the intervention group had significant improvement or maintenance of cognitive health measured by neuropsychologic test battery, compared with the control group.²⁰ Similar trials have been launched, including the US-POINTER study.^a

In a small randomized study of 170 Australian participants without dementia at baseline, home-based physical activity improved the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores over 18 months.²¹ In another study of 149 adults randomized to a community participation activity at elementary schools for 15 hours/week or a wait-listed control arm, the active participants had greater improvements in executive function and memory.²²

Individuals With Mild or Unspecified Cognitive Impairment

There are 7 meta-analyses or systematic reviews regarding physical and cognitive activity in people with unspecified cognitive impairment,^14,16,23-27 and 11 in people with MCI.^9,12,28-36 These studies reach consensus that physical, cognitive, and multicomponent activity improve cognitive abilities, executive function, attention and delayed recall (Table). Some report improvement in ADL, function, and gait leading to fall reduction.^{9,23,24,26,27,29,36} Analyses of exercise effects on behavior suggest reduced neuropsychiatric symptoms leading to improvement of quality of life.²⁵ Meta-analyses of mechanism of benefit of physical activity showed reduced oxidative stress and changes in the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF).³⁷

Individuals With Unspecified or AD Dementia

The overall results in 12 meta-analyses and systematic reviews of studies on physical and cognitive activity in adults with AD^30,32,38-47 and 8 of people with unspecified dementia^{27,36,39,42,44,48-50} are similar to studies done in cognitively healthy individuals and those with MCI. Analyses were done in home-based,⁴⁸ community-dwelling,^40,50 and residential-care⁴⁴ settings. Interventions included structured physical activities, leisure-time activities, cognitive activities, and simultaneous multicomponent activities (Table). These studies suggest physical activity provides overall improvement in cognitive function and subcognitive subdomains. Improvements in ADLs, functional abilities, gait, and fall reduction were also observed. Improvement in mood and behavior and reduction of behavioral and psychologic symptoms of dementia were seen. Some analyses showed delay in functional decline in people with dementia and reductions in caregivers’ stress.

Other Specific Dementias

Evidence of benefits of physical and/or cognitive interventions is scarce for other specific dementias. We did not find any systematic reviews or meta-analyses on effects of physical or cognitive activity for people with corticobasal degeneration (CBD), frontotemporal dementia (FTD), or vascular dementia. In a randomized clinical trial of an exercise intervention for people with familial FTD, physical exercise slowed rates of clinical decline and brain atrophy.⁵¹ A clinical trial of exercise for people with advanced cerebrovascular disease showed exercise reduced the incidence of all-cause dementia, AD, and vascular dementia.⁵² Meta-analysis of supported and robot-assisted gait training, gaze training, balance re-education, and auditory-cued motor training, however, did not demonstrate improvement in people with progressive supranuclear palsy (PSP).⁵³

A systematic review evaluating the effect of exercise in people with dementia with Lewy bodies (DLB) showed improvement in gait speed with activity,⁵⁴ and a study using deep brain stimulation, transcranial magnetic stimulation, and electroconvulsive therapy (ECT) as well as physical activity showed improvement in attention and memory.⁵⁵ A protocol for a study of exercise in individuals with DLB has been published.⁵⁶ A recent study on the effect of exercise on parkinsonism showed higher daily physical activity was associated with less severe parkinsonism even after controlling for brain pathologies.⁵⁷ A systematic review of aerobic exercise in people with Parkinson disease reported that aerobic exercise improved gait, cognition, and quality of life and reduced depression.⁵⁸

Conclusion

Proteinopathies are not always directly correlated with clinical symptoms of cognitive decline. Complex and intricate brain changes at the metabolic level lead to symptoms of dementia. Early-life enrichment, cognitive enrichment, and physical activity have positive effects on late-life cognitive health and brain resilience to avert cognitive decline even in the presence of brain pathology. This concept is further bolstered by studies in which removal and suppression of proteins in brain pathology related to dementia have not produced any meaningful cure in various neurodegenerative dementias. The current pharmacologic landscape is only minimally effective in the mitigation of symptoms. Without any disease-modifying agents and a growing population of people over age 65, the role of risk factor reduction and cognitive and physical activity to improve cognitive health and delay cognitive decline are even more pertinent. Clinicians should strongly advocate adopting a healthy lifestyle to their patients at clinic visits starting from an early age to prevent and mitigate cognitive decline.