Effects of Nordic walking in Alzheimer's disease: A single-blind randomized controlled clinical trial

The study addresses whether a 24-week Nordic walking (NW) program improves cognitive function in patients with mild to moderate Alzheimer’s disease (AD). Given the lack of effective disease-modifying therapies, modifiable risk factors such as physical inactivity are key targets for prevention and management. Prior evidence links physical activity to reduced risk and slower progression of cognitive decline, with proposed mechanisms including increased cerebral blood flow, neurogenesis/synaptogenesis, and antioxidant effects. NW, an aerobic walking modality using poles to engage upper body musculature and enhance stability, has shown benefits in other conditions and in older adults, but its role in AD is underexplored, with only a single short-duration study assessing limited cognitive domains. The study’s purpose is to evaluate the impact of 24 weeks of NW on cognitive performance in AD.

Observational and interventional research indicates physical activity is associated with reduced risk of cognitive decline and AD onset, and benefits brain health even when initiated later in life. Mechanistic literature suggests exercise increases cerebral perfusion, neurotransmitter release, neurogenesis/synaptogenesis, and antioxidant defenses. NW elicits greater heart rate, oxygen consumption, and caloric expenditure than regular walking and offers stability benefits, facilitating exercise among older adults. NW has improved functional mobility and quality of life in Parkinson’s disease and cognitive functions (executive functions, processing speed, spatial memory) in older adults. Only one prior 3-month NW study in AD assessed limited domains with global cognition (MoCA) unchanged. Proposed biological mediators include VEGF and BDNF; some studies show NW increases circulating VEGF more than traditional walking, while BDNF responses are mixed. NW has also favorably modulated lipid profiles and antioxidant capacity in various populations, factors relevant to AD pathophysiology. However, meta-analyses show mixed findings regarding optimal exercise type, intensity, and duration for cognitive benefits in dementia.

Design: Single-blind, randomized, controlled clinical trial. Participants: 30 patients with mild/moderate AD recruited from ASReM Day Center and CeRMI, University of Molise (Campobasso, Italy). Inclusion criteria: Probable AD with documented decline per NIA-AA criteria; MMSE 18–24 (mild) or 9–17 (moderate); CDR >1. Exclusion criteria: GDS >6; inability to perform 6-minute walk test; comorbidities precluding exercise; brain imaging excluding other causes (e.g., multiple/extensive infarcts, severe WMH, meningioma, glioma, subdural hematoma, vascular malformation, normal pressure hydrocephalus). Ethics: Approved by ASReM Ethics Committee (protocol 142-19/09/2019); written informed consent obtained. Randomization and interventions: Patients randomized (computer-generated) to control group (CG, n=15) or experimental group (EG, n=15). Both groups received: 2 h/week formal ROT with physiotherapists/occupational therapists; 8 h/week informal ROT with psychologists and socio-health professionals; 4 h/week music therapy; 2 h/week motor, proprioceptive, and postural rehabilitation. EG additionally performed supervised NW twice weekly for 60 min/session over 24 weeks (10 min warm-up/stretching, 40 min NW, 10 min cool-down/stretching). NW intensity was guided by personal perceived exertion (non-standardized intensity). Assessments: Extensive neuropsychological battery with age/education/sex-adjusted scores: MMSE (primary outcome: 24-week change), FAB, RAVLT immediate and delayed recall, Prose Memory Test (PMT), Attentional Matrices, Raven’s Colored Progressive Matrices (CPM), Stroop Word-Color Interference Test (SWCT) completion time and errors, Copying Geometric Drawings (CGD). Functional and quality of life measures: ADL, IADL, QoL-AD (secondary outcomes: 24-week changes). Statistical analysis: Data inspected for normality (plots; Shapiro-Wilk, Kolmogorov-Smirnov), with transformations applied as needed. Normally distributed variables summarized as mean±SD and compared with independent-samples t-tests; non-normal variables summarized as median (IQR) and compared with Mann-Whitney U tests. Categorical variables analyzed with chi-square tests. Primary and secondary outcomes analyzed as between-group comparisons of 24-week change scores (Mann-Whitney U). Significance set at P<0.05. Subgroup analysis: patients with mild AD only (EG n=9; CG n=8).

- Completion: 22/30 completed 24 weeks (EG n=9; CG n=13). Baseline demographics/clinical features and baseline test scores did not differ significantly between groups. - Primary outcome (MMSE): No significant between-group difference in 24-week change (p=0.20). Trend: CG decreased; EG remained essentially unchanged. - Secondary cognitive outcomes with significant between-group differences favoring EG: - FAB (executive functions): p=0.04; CG worsened, EG improved. - RAVLT delayed recall (verbal episodic memory): p=0.02; CG decreased, EG unchanged. - CPM (visuospatial reasoning): p=0.002; CG worsened, EG improved. - SWCT completion time (selective attention/processing speed): p=0.006; CG completion time worsened, EG improved (lower time). - Secondary outcomes without significant differences: RAVLT immediate recall, Attentional Matrices, PMT, CGD, SWCT errors, QoL-AD, ADL, IADL (all p>0.05). - Mild AD subgroup analysis (EG n=9; CG n=8): Results similar except FAB no longer showed a significant between-group difference.

Findings indicate that a 24-week NW program can enhance specific cognitive domains in AD—executive function, processing speed/attention, visuospatial reasoning, and verbal episodic memory—despite no significant effect on global cognition (MMSE) over the same period. Improvements align with prior NW studies in older adults showing gains in executive functioning, processing speed, and spatial memory, and with broader literature on exercise-related cognitive benefits. Lack of QoL and functional gains contrasts with some NW studies in general elderly populations, potentially reflecting measurement challenges in AD (anosognosia, caregiver-reported biases), the short intervention period, or concurrent standard therapies in both groups. Proposed mechanisms include increased regional brain metabolism and grey matter volume with exercise, and NW’s multicomponent nature combining cardiovascular exertion and coordination demands. Molecular mediators such as VEGF and BDNF may contribute, alongside favorable changes in lipid profile and oxidative stress; however, biomarker findings with NW are mixed. Overall, NW appears to be a feasible, safe adjunct that may decelerate decline in select cognitive domains in mild/moderate AD.

A 24-week NW intervention improved visuospatial reasoning, verbal episodic memory, selective attention, and processing speed in patients with AD, while global cognition (MMSE) remained stable compared to a decline in controls but without a significant between-group difference. NW shows promise as an adjunctive, safe strategy to slow domain-specific cognitive decline in mild/moderate AD. Future research should employ larger samples, standardized training intensity, and longer follow-up to determine durability, dose–response, and effects on global cognition, daily functioning, and quality of life.

- Small sample size with attrition (22/30 completed), limiting power and generalizability. - NW intensity not standardized (perceived exertion-based), introducing variability in training dose. - Relatively short intervention duration (24 weeks) for detecting changes in global cognition and functional outcomes. - Single-blind design. - At completion, only mild AD patients were present in the EG, necessitating subgroup analyses and potentially indicating group imbalance.