Mild Cognitive Impairment (MCI) is widely recognized as an intermediate stage between normal cognitive ageing and dementia, particularly Alzheimer’s disease. Individuals with MCI exhibit objective cognitive deficits greater than expected for age and education but retain independence in basic activities of daily living. Among the subtypes, amnestic MCI is of particular clinical importance due to its high annual conversion rate to Alzheimer’s disease, estimated at 10–15%.

Despite advances in understanding the neurobiology of cognitive decline, pharmacological treatment options for MCI remain limited. Cholinesterase inhibitors and memantine have not demonstrated consistent benefits in delaying disease progression, and disease-modifying therapies targeting amyloid and tau pathology have shown modest or inconclusive results. This therapeutic gap has intensified interest in non-pharmacological strategies that may preserve cognitive function and delay neurodegeneration.

Lifestyle factors, particularly physical activity, have emerged as key modulators of cognitive health. Epidemiological studies consistently demonstrate that physically active individuals have a lower risk of cognitive decline and dementia. Among various forms of physical activity, aerobic exercise has shown the most consistent association with cognitive benefit, likely due to its effects on cardiovascular fitness, cerebral perfusion, metabolic regulation, and neuroplasticity.

Aerobic exercise enhances cerebral blood flow, upregulates neurotrophic factors such as brain-derived neurotrophic factor (BDNF), reduces systemic inflammation, and improves insulin sensitivity. These effects are particularly relevant in MCI, where vascular dysfunction, neuroinflammation, and metabolic impairment contribute to cognitive decline. However, randomized controlled trials specifically examining structured aerobic exercise in clinically diagnosed amnestic MCI populations remain limited, particularly in low- and middle-income settings.

The present study was designed to evaluate the effect of structured aerobic exercise training on global and domain-specific cognitive outcomes in individuals with amnestic MCI. We hypothesized that aerobic exercise would result in significant cognitive improvement compared to a matched non-aerobic control intervention and that cognitive gains would correlate with improvements in cardiorespiratory fitness.

This study was a prospective, randomized controlled trial conducted over 18 months, including participant recruitment, intervention, and follow-up. Study Setting and Participants Participants were recruited from the Neurology and Psychiatry outpatient departments of a tertiary care teaching hospital. Individuals aged 55–75 years were screened for eligibility. Inclusion Criteria Participants were included if they met criteria for amnestic MCI, defined by: • Subjective memory complaint reported by the participant or informant • Objective impairment in episodic memory (≥1.5 SD below age- and education-adjusted norms) • Preserved basic activities of daily living • Clinical Dementia Rating (CDR) global score of 0.5 • MMSE score 24–28 or MoCA score 18–25 • Medical clearance for physical activity Exclusion Criteria Exclusion criteria included: • Diagnosis of dementia • Major psychiatric illness • Uncontrolled cardiovascular, respiratory, or musculoskeletal disease • Participation in structured exercise programs within the previous six months Sample Size Based on an assumed effect size of 0.5, α = 0.05, and power = 0.8, a minimum of 64 participants was required. Accounting for potential attrition, 80 participants were enrolled. Randomization Participants were randomized using block randomization into AET or SAT groups in a 1:1 ratio. Intervention AAGYE Aerobic Exercise Training Group: Participants engaged in supervised aerobic exercise five days per week for 12 weeks. Each session consisted of warm-up, 30–40 minutes of brisk walking or treadmill exercise, and cool-down. Exercise intensity was maintained at 60–75% of age-predicted maximum heart rate and progressively increased during the initial weeks. Stretching and Toning Control Group: The control group participated in supervised stretching, balance, and light toning exercises matched for frequency and duration but maintained below aerobic intensity (<50% HR reserve). Outcome Measures Cognitive Assessment: • Global cognition: MoCA, MMSE • Executive function: Trail Making Test-A and B, Stroop Test • Attention and working memory: Digit Span forward and backward Cardiorespiratory Fitness: • Six-minute walk test (6-MWT) Assessments were conducted at baseline, 6 weeks, and 12 weeks. Statistical Analysis Data were analyzed using SPSS version 31.0. An intention-to-treat approach was employed. Baseline differences were assessed using independent t-tests and chi-square tests. Between-group comparisons of post-intervention outcomes were conducted using ANCOVA with baseline values as covariates. Effect sizes were calculated using partial eta squared (ηp²). A p-value <0.05 was considered statistically significant.

A total of 80 participants were randomized, with comparable baseline sociodemographic, clinical, cognitive, and fitness characteristics between groups (Tables 1–4). Attrition was minimal and balanced between groups

OHTABLE 1. Baseline Sociodemographic Characteristics of Study Participants

TABLE 2. Baseline Clinical and Cognitive Characteristics

TABLE 3. Baseline Neuropsychological Test Scores

TABLE 4. Baseline Cardiovascular Fitness Parameters

The present randomized controlled trial demonstrates that structured aerobic exercise training produces significant and clinically meaningful improvements in cognitive function among individuals with amnestic MCI. Improvements were observed across global cognition, executive function, attention, and working memory, with early onset and sustained benefit.

These findings are consistent with previous studies demonstrating cognitive benefits of aerobic exercise in older adults and individuals with cognitive impairment. However, the present study extends existing evidence by demonstrating robust cognitive improvement within a relatively short intervention period and by establishing a strong association between fitness gains and cognitive outcomes.

Executive function showed the greatest improvement, consistent with the hypothesis that aerobic exercise preferentially benefits prefrontal cortical networks through enhanced cerebral perfusion and neuroplasticity. Improvements in attention and working memory further suggest enhanced frontoparietal network efficiency.

The strong correlation between cardiorespiratory fitness improvement and cognitive gain supports a dose–response relationship, strengthening causal inference.

Aerobic exercise likely exerts its cognitive effects through multiple interacting mechanisms, including improved cerebrovascular function, increased neurotrophic support, reduced inflammation, and enhanced metabolic regulation.

Importantly, aerobic exercise offers advantages over pharmacological therapies by targeting multiple pathogenic pathways simultaneously and by improving overall physical and psychological health. The favorable safety profile and feasibility of exercise interventions further enhance their clinical applicability.

Strengths and Limitations

Strengths of the study include its randomized controlled design, well-characterized MCI population, structured intervention, and comprehensive cognitive assessment. Limitations include modest sample size, short follow-up duration, and absence of biomarker or neuroimaging endpoints.

Structured aerobic exercise training significantly improves cognitive performance in individuals with amnestic Mild Cognitive Impairment. The observed benefits span multiple cognitive domains, emerge early during intervention, and are closely linked to improvements in cardiorespiratory fitness. Aerobic exercise should be considered a core non-pharmacological strategy in the management of early cognitive impairment and dementia prevention.

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