1. Introduction
Alzheimer’s disease (AD) is the most prevalent type of dementia whose main neuropathological features are cerebral amyloidosis and tauopathy. Non-modifiable risk factors include age, APOE-ε4 allele, and family history; modifiable risk factors are essentially cardiovascular risk factors, such as midlife hypertension, midlife obesity, diabetes, smoking, and physical inactivity. In the absence of effective disease-modifying therapies for AD, much attention has been paid to the modifiable risk factors, whose recognition upholds primary prevention in the management of dementia. Indeed, the Lancet International Commission on Dementia Prevention, Intervention and Care estimated that interventions on modifiable risk factors could prevent approximately 35% of dementia cases.
Longitudinal studies have shown an association between physical activity and the risk of cognitive decline, suggesting that exercise can delay the onset of AD in a dose-dependent manner. Furthermore, it is worth noting that also late-onset exercise interventions improve brain health and that physical activity can be beneficial in both brain aging and AD-neurodegeneration. Specifically, it has been shown that exercise can increase cerebral blood flow, improve neurotransmitter release thereby facilitating neurogenesis and synaptogenesis, and promote the synthesis of antioxidant molecules, effects that oppose brain changes related to aging and AD. Therefore, physical activity has shown promise in the prevention and treatment of AD.
Nordic walking (NW) is a particular type of aerobic exercise where simple walking is enriched by the use of specifically ergonomically designed poles, with the advantage of active involvement in the upper body and arms, resulting in a higher heart rate, oxygen consumption, and caloric expenditure compared to regular walking, and a decrease in the perceived level of exertion. The use of NW poles is valuable, as they provide stability that can promote physical activity, even among the elderly. The effects of NW have been evaluated in several medical conditions such as Parkinson’s disease (PD), which seems to play an important role in rehabilitation because of its potential to improve functional mobility, gait, and quality of life. Moreover, recent studies have shown that regular NW training leads to improved cognitive function in older adults. To date, a single 3-month NW training study has been conducted in patients with AD, and only a few cognitive domains have been investigated. Therefore, detailed scientific data on the role of NW in AD are still lacking.
Our study aimed to evaluate the effects of 24-week NW training on cognitive function in patients with mild/moderate AD to implement therapeutic strategies for the management of dementia.
2. Materials and methods
2.1. Study design and patients
The study was a single-blind, randomized, controlled clinical trial involving 30 patients with mild/moderate AD. Patients were enrolled from among individuals accessing the Day Center for Alzheimer’s Patients of the Molise Region Health Authority (ASReM) and the Centre for Research and Training in Medicine of Aging (CeRMI) of the University of Molise (Campobasso, Italy). Eligibility criteria were: diagnosis of “probable AD with documented decline”, according to criteria of the NIA-AA (National Institute on Aging and Alzheimer’s Association), Mini-Mental State Examination (MMSE) between 18 and 24 for mild AD, MMSE between 9 and 17 for moderate AD, and Clinical Dementia Rating (CDR) scale >1. The exclusion criteria were as follows: Geriatric Depression Scale (GDS) >6 and inability to perform a 6-min walk test, as well as the presence of other comorbidities that prevented adherence to the physical activity program. All the patients underwent blood tests and brain imaging to rule out other possible causes of dementia. Patients with multiple or extensive infarcts or severe white matter hyperintensities were excluded, as were those with other pathological findings such as meningioma, glioma, subdural hematoma, vascular malformation, or normal pressure hydrocephalus.
The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and approved national and international guidelines for human research. The Ethics Committee of ASReM reviewed and approved this study (protocol n. 142–19/09/2019). Written informed consent was obtained from all the participants or their caregivers.
2.2. Randomization and activity program
The patients were randomly divided into two groups of 15 patients according to a computer-generated randomization list: the control group (CG) and the experimental group (EG). Both CG and EG patients underwent 2 h a week of cognitive re-education based on formal Reality Orientation Therapy (ROT) with physiotherapists or occupational therapists; 8 h a week of cognitive re-education based on informal ROT with psychologists and socio-health professionals; 4 h a week of music therapy with music therapists; 2 h a week of motor, proprioceptive and postural rehabilitation with physiotherapists. The 15 EG patients performed training sessions of 60 min twice a week, under the supervision of a specialized trainer, consisting of 10 min of warm-up with stretching exercises, 40 min of NW, and 10 min of cool down with stretching exercises. NW training was not standardized in terms of intensity level but was carried out on the personal perception of maximum exertion. All activities were performed for 24 weeks.
2.3. Neuropsychological assessment and evaluation of daily activities and quality of life
All patients underwent extensive neuropsychological assessment, including the MMSE, Frontal Assessment Battery (FAB), immediate and delayed recalls in the Rey’s Auditory Verbal Learning Test (RAVLT), Prose Memory Test (PMT), Attentional Matrices Test, Raven’s Colored Progressive Matrices (CPM), completion time and errors in the short version of the Stroop Word-Color Interference test (SWCT), and Copying Geometric Drawings (CGD). All raw test scores were adjusted for age, educational level, and sex. Activities of daily living (ADL), instrumental activities of daily living (IADL), and quality of life in Alzheimer’s disease (QoL-AD) were also assessed. The 24-week change in the MMSE score was the primary outcome, whereas the 24-week change in the remaining assessment scores was the secondary outcome.