The review draws a careful distinction between physical activity, defined as any bodily movement produced by skeletal muscles that raises energy expenditure above resting levels, and exercise, which is planned, structured, and repetitive movement aimed at improving or maintaining physical fitness. In dementia research, exercise interventions typically fall into several categories, each targeting distinct physiological and cognitive outcomes. Aerobic exercise, the most commonly studied modality, includes walking, swimming, cycling, and low-impact group activities, and has been associated with improvements in cerebral blood flow and overall brain health. Resistance training counters age-related declines in muscle mass, strength, and physical function, and in individuals with dementia has been linked to improvements in functional performance that may indirectly support cognition through enhanced metabolic health. Balance and flexibility practices such as yoga and tai chi improve postural stability and coordination, reducing fall risk in a population where falls remain a major concern.

Perhaps the most consistent finding across the literature is that multicomponent exercise programs, which combine aerobic, strength, and balance training, tend to produce the most reliable improvements in both cognitive and functional outcomes. These programs target multiple physiological systems simultaneously, and the review notes that no single type of exercise appears universally superior. Instead, a combination tailored to individual capabilities and preferences is likely to provide the greatest benefit. Functional training built around daily activities also shows promise for improving independence and quality of life, and is highly practical and adaptable to real-world settings.

On the cognitive front, randomized trials and meta-analyses report small but consistent improvements in executive function and attention, though effects on memory are less uniform, with some studies showing benefit and others minimal change. A recurring pattern is that individuals in earlier stages of cognitive decline respond better to exercise interventions, possibly reflecting greater neural reserve or a greater capacity to engage in structured programs. The review emphasizes that while exercise is unlikely to produce dramatic cognitive improvements, the observed benefits are clinically relevant, particularly when considered alongside broader effects on physical and psychological health. Differences in study design, including the type, intensity, and duration of exercise, make direct comparisons difficult, but the direction of the evidence is clear.

The review also highlights that dementia is not a single entity, and that the response to exercise may vary across subtypes. Alzheimer’s disease, the most common form, is characterized by amyloid-beta plaque deposition, neurofibrillary tangles of hyperphosphorylated tau, and progressive neuronal loss, particularly in the hippocampus. Exercise is thought to primarily influence neurodegenerative pathways in this subtype, including neuroplasticity and synaptic function, with improvements reported in executive function and attention. Vascular dementia, by contrast, is more closely linked to cerebrovascular pathology, and may respond more directly to interventions that improve cardiovascular and metabolic health. Physical activity, through its effects on blood pressure, insulin sensitivity, endothelial function, and cerebral perfusion, may have a particularly important role in this subgroup. Mixed dementia, which combines neurodegenerative and vascular components, may benefit from both mechanisms, although evidence remains limited.

Beyond cognition, the benefits of exercise extend to daily functioning and psychological well-being. The Lifestyle Interventions and Independence for Elders study showed that regular exercise improves mobility, balance, and overall physical performance, changes that directly influence the ability to perform activities of daily living and maintain independence. Structured programs incorporating strength and balance training are generally effective in reducing fall risk, though the way exercise is delivered matters: the LiFE study demonstrated that a lifestyle-integrated functional exercise approach significantly reduced fall rates, whereas traditional structured programs showed less consistent benefits. There is also growing evidence that physical activity can reduce depressive symptoms, agitation, and anxiety in people with dementia, and may improve sleep patterns, though this area remains less well studied.

The biological mechanisms underlying these benefits are complex and likely multifactorial. One of the most widely discussed pathways involves the upregulation of neurotrophic factors, particularly brain-derived neurotrophic factor, or BDNF, which plays a key role in neuronal survival, synaptic plasticity, and learning. BDNF is highly expressed in the hippocampus and cerebral cortex, where it regulates neuronal survival, differentiation, synaptic plasticity, and long-term potentiation, processes essential for learning and memory. Exercise-induced increases in BDNF activate the tropomyosin receptor kinase B, triggering intracellular signaling pathways that enhance dendritic spine formation, facilitate hippocampal neurogenesis, strengthen synaptic connectivity, and improve neuronal resilience against age-related degeneration. Experimental and clinical studies consistently demonstrate that aerobic exercise increases circulating and hippocampal BDNF concentrations, although the magnitude of this response varies according to exercise intensity, duration, and disease stage.

Other neurotrophic factors contribute to the neuroprotective effects of exercise. Insulin-like growth factor-1 readily crosses the blood-brain barrier and acts synergistically with BDNF to stimulate hippocampal neurogenesis and synaptic plasticity. Vascular endothelial growth factor promotes angiogenesis and improves cerebral perfusion, enhancing oxygen and nutrient delivery to metabolically active brain regions. Nerve growth factor and glial cell line-derived neurotrophic factor further support neuronal survival and repair by maintaining cholinergic and dopaminergic neuronal function. Collectively, these factors contribute to enhanced neuronal resilience and may partly explain the beneficial effects of long-term exercise on cognitive function.

Recent evidence also points to a muscle-brain axis, whereby skeletal muscle functions as an endocrine organ, releasing biologically active molecules called myokines during physical exercise. Among these, irisin, generated through cleavage of fibronectin type III domain-containing protein 5, has received considerable attention because it stimulates hippocampal BDNF expression and promotes synaptic plasticity. Other exercise-responsive myokines, including cathepsin B and meteorin-like protein, have been implicated in neuronal differentiation, neurogenesis, and memory enhancement. Exercise-induced lactate functions not only as an energy substrate but also as a signaling molecule capable of stimulating BDNF production and improving neuronal metabolism. These observations support the concept that regular physical activity exerts systemic effects extending beyond skeletal muscle to preserve cognitive function and delay neurodegenerative processes.

Exercise also modulates neuroinflammation, a key pathological mechanism underlying dementia. Persistent activation of microglia and astrocytes promotes the release of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, resulting in synaptic dysfunction, oxidative stress, and progressive neuronal loss. Regular physical exercise attenuates these inflammatory processes by reducing circulating pro-inflammatory mediators while increasing anti-inflammatory cytokines such as interleukin-10. Exercise also suppresses oxidative stress by enhancing endogenous antioxidant defense systems, thereby limiting neuronal injury and preserving synaptic integrity. Through these combined anti-inflammatory and antioxidant actions, exercise creates a favorable cerebral microenvironment that supports neuronal survival and cognitive function.

The vascular and metabolic mechanisms are equally compelling. Regular aerobic exercise enhances endothelial function, increases cerebral blood flow, and improves vascular reactivity, facilitating oxygen and nutrient delivery to vulnerable brain regions. Improved cerebral perfusion may reduce ischemic injury and contribute to the preservation of cognitive function, particularly in individuals with vascular dementia. Exercise also enhances insulin sensitivity, improves glucose utilization, reduces central adiposity, and favorably modifies lipid metabolism, thereby reducing several established risk factors for dementia. Furthermore, regular physical activity stimulates mitochondrial biogenesis and reduces oxidative stress, promoting efficient neuronal energy metabolism and decreasing apoptosis. These adaptations collectively contribute to improved brain resilience.

The metabolic connection is particularly significant given increasing recognition that dementia, especially Alzheimer’s disease, is closely linked to metabolic dysfunction. Conditions such as type 2 diabetes, insulin resistance, obesity, and dyslipidemia have been consistently associated with an increased risk of cognitive decline. In this context, dementia has even been described by some as a metabolic disease of the brain, or type 3 diabetes, reflecting the role of impaired glucose metabolism and insulin signaling in its pathogenesis. Insulin plays a major role in the central nervous system, influencing synaptic plasticity, neuronal survival, and memory processes, and in states of insulin resistance these functions may be compromised. Chronic hyperglycemia and associated metabolic disturbances can promote oxidative stress, advanced glycation end-product formation, and vascular damage, all of which may accelerate cognitive decline. Exercise, by improving metabolic regulation, may translate into better cognitive outcomes, particularly in individuals with or at risk of type 2 diabetes.

From a clinical prescription standpoint, most randomized trials have employed moderate-intensity aerobic exercise, typically performed three to five times per week, often combined with resistance or balance training. Programs lasting at least 12 to 24 weeks appear more likely to demonstrate measurable benefits, and multicomponent interventions tend to yield more consistent outcomes compared to single-modality approaches. Exercise prescriptions should be individualized, taking into account disease severity, comorbidities, baseline functional status, and patient preferences. In early stages, individuals may participate in structured and supervised programs, whereas in more advanced stages, simpler and more supported activities may be more appropriate. Supervision is often a key factor influencing both safety and adherence, and interventions delivered in group settings or with caregiver involvement may enhance engagement and sustainability.

Despite the growing evidence, considerable heterogeneity across studies remains a challenge. Differences in study design, participant characteristics, and intervention protocols make it difficult to draw direct comparisons or establish definitive conclusions. Variability exists in the type of exercise performed, its intensity and duration, and the stage of dementia among participants. Outcome measures are not always consistent, and adherence is often underreported but can significantly influence results. Recognizing these methodological limitations is important when interpreting existing evidence and highlights the need for more standardized and well-designed trials.

From a public health perspective, the integration of physical activity into dementia care has important implications. As the global burden continues to rise, particularly in low- and middle-income countries where healthcare resources are often limited, there is an urgent need for interventions that are both effective and scalable. Exercise-based interventions are relatively low-cost and can be adapted to a variety of settings, including community centers, primary care systems, and home-based environments. However, successful implementation requires more than evidence of efficacy; factors such as safety, accessibility, cultural acceptability, and availability of trained personnel play a crucial role. Community-based programs and caregiver-supported interventions may offer practical solutions to improve reach and adherence, and integrating physical activity into existing healthcare frameworks could help bridge the gap between research and real-world practice.

Ultimately, the review concludes that physical activity and structured exercise offer a practical and accessible approach to improving outcomes in individuals with dementia. While cognitive benefits are generally modest, consistent improvements are seen in functional ability, mobility, and psychological well-being, all central to maintaining quality of life. These effects likely arise from a combination of neurobiological, vascular, and metabolic mechanisms, with additional relevance in individuals with coexisting conditions such as diabetes. Despite variations in study design and challenges related to adherence and implementation, increasing physical activity remains a low-cost, adaptable intervention that can be integrated into routine care, and with further refinement, has the potential to play a meaningful role in the prevention and management of dementia.

Subject of Research: Physical activity and exercise as non-pharmacological interventions in dementia

Article Title: Physical activity and exercise in dementia: clinical relevance and emerging insights

Article References: Pramodkumar, T. A., & Mohan, V. (2026). Physical activity and exercise in dementia: clinical relevance and emerging insights. Frontiers in Dementia, 5, Article 1843904. https://doi.org/10.3389/frdem.2026.1843904

Image Credits: AI Generated

DOI: 10.3389/frdem.2026.1843904

Keywords: dementia, exercise, physical activity, Alzheimer's disease, BDNF, neuroplasticity, vascular dementia, metabolic health, type 2 diabetes, non-pharmacological interventions, Physical, activity