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

Alzheimer's disease (AD), the most common type of dementia, is characterized by cerebral amyloidosis and tauopathy. Non-modifiable risk factors include age, APOE-ε4 allele, and family history, while modifiable factors such as hypertension, obesity, diabetes, smoking, and physical inactivity are crucial targets for prevention. The Lancet International Commission on Dementia Prevention estimated that addressing modifiable risk factors could prevent approximately 35% of dementia cases. Longitudinal studies have linked physical activity to a reduced risk of cognitive decline, suggesting a dose-dependent effect on delaying AD onset. Even late-onset exercise interventions have demonstrated benefits for brain health. Exercise enhances cerebral blood flow, neurotransmitter release, neurogenesis, synaptogenesis, and antioxidant synthesis, counteracting age-related and AD-related brain changes. Nordic walking (NW), an aerobic exercise involving poles, increases heart rate, oxygen consumption, and caloric expenditure compared to regular walking, while reducing perceived exertion. Its value lies in its stability, facilitating activity in the elderly. While NW's benefits have been observed in conditions like Parkinson's disease and improved cognitive function in older adults, data on its role in AD is limited. This study aimed to evaluate the effects of a 24-week NW training program on cognitive function in patients with mild/moderate AD.

Existing research highlights the association between physical activity and reduced risk of cognitive decline and AD. Studies show that exercise, even when initiated later in life, can improve brain health by increasing cerebral blood flow, neurogenesis, and antioxidant production. Nordic walking (NW) has demonstrated benefits in other conditions and in older adults, improving cognitive function, but data specifically on its impact on AD patients remains scarce. A previous study explored the effects of a 3-month NW training program on a limited set of cognitive domains in AD patients, emphasizing the need for more comprehensive research.

This study employed a single-blind, randomized controlled clinical trial design with 30 patients diagnosed with mild/moderate AD according to NIA-AA criteria. Patients were recruited from an Alzheimer's Day Center and a research center in Italy. Inclusion criteria included a diagnosis of probable AD, MMSE scores between 18-24 (mild) or 9-17 (moderate), and CDR scale >1. Exclusion criteria involved GDS >6, inability to complete a 6-minute walk test, or comorbidities hindering participation. All patients underwent blood tests and brain imaging to rule out other causes of dementia. The 30 participants were randomly assigned to either a control group (CG, n=15) or an experimental group (EG, n=15). Both groups received 2 hours/week of formal Reality Orientation Therapy (ROT), 8 hours/week of informal ROT, 4 hours/week of music therapy, and 2 hours/week of motor rehabilitation. The EG additionally underwent two 60-minute NW training sessions per week for 24 weeks, including warm-up, NW exercise, and cool-down. Neuropsychological assessment encompassed MMSE, FAB, RAVLT (immediate and delayed recall), PMT, Attentional Matrices Test, CPM, SWCT (completion time and errors), and CGD. ADL, IADL, and QoL-AD were also assessed. The primary outcome was the 24-week change in MMSE scores, while secondary outcomes included changes in other assessment scores. Data analysis used SPSS version 17.0, employing t-tests or Mann-Whitney U tests based on data distribution. Statistical significance was set at p<0.05.

Of the initial 30 participants, 22 (9 in EG, 13 in CG) completed the 24-week program and were included in the final analysis. There were no significant baseline differences between groups. While the primary outcome (24-week change in MMSE scores) showed no significant difference between groups, the EG showed improvements in several secondary outcomes. Specifically, the EG demonstrated significant improvements in FAB scores, RAVLT delayed recall scores, SWCT completion time, and CPM scores. These improvements suggest positive effects of NW on executive functions, verbal episodic memory, processing speed, and visual-spatial reasoning. The CG showed a decline in several of these cognitive domains over the 24-week period. A secondary analysis comparing only those with mild AD (9 in EG, 8 in CG) yielded similar results, with the exception of the FAB score where the difference was no longer significant. No significant between-group differences were observed for RAVLT immediate recall, Attentional Matrices test, PMT, CGD, SWCT errors, QoL-AD, ADL, and IADL.

The findings suggest that a 24-week NW training program can positively impact specific cognitive domains in patients with AD, particularly executive functions, memory, attention, and processing speed, even without significant changes in overall cognitive function as measured by the MMSE. The lack of improvement in the MMSE score may be attributed to the slow progression of the disease or the relatively short intervention duration. The observed benefits align with previous research demonstrating NW's positive effects on cognitive function in older adults. However, the lack of significant improvement in FAB scores when the analysis was restricted to patients with mild AD warrants further investigation. The absence of differences in QoL-AD, ADL, and IADL may reflect the challenges in assessing these aspects in AD patients due to anosognosia and caregiver bias. The study’s limitations (small sample size and lack of NW intensity standardization) necessitate further research with larger samples and standardized NW protocols.

This study suggests that 24-week NW training may improve specific cognitive functions in patients with AD, particularly executive functions, verbal episodic memory, processing speed, and visual-spatial reasoning. Although limited by sample size and lack of NW intensity standardization, the results are promising and suggest that NW, combined with other interventions, could help slow cognitive decline. Further studies with larger sample sizes, longer intervention durations, and standardized NW intensity are necessary to confirm these findings and explore the long-term effects of NW on cognitive function and overall quality of life in AD patients.

The main limitations of this study include the relatively small sample size and the absence of NW intensity standardization. The small sample size may have reduced the power to detect statistically significant differences in some outcomes. The lack of standardized NW intensity makes it challenging to determine the optimal intensity for cognitive benefits. A longer training period might be needed to observe more pronounced effects on global cognitive function. Further research is needed to address these limitations and to better understand the long-term effects of NW on AD progression.