This meta-analysis aimed to assess the effect of exercise interventions on functional mobility among older adults with cognitive impairments such as dementia or mild cognitive impairment, followed by further investigation on the possible moderators of exercise-induced effects on this outcome.

A meta-analysis of controlled trials on exercise interventions reporting functional mobility outcomes was conducted. PubMed, Embase, EBSCO, SPORTDiscus, and Web of Science were searched for relevant studies published in English-language journals through July 2024.

Clinical and community settings across 15 countries, including a total of 1104 older adults with cognitive impairment, were involved in the study.

We computed pooled effect sizes based on standardized mean difference (SMD) using the random-effects models. The subgroup analyses and meta-regression were conducted for multiple moderating variables (eg, exercise, sample, and study characteristics). The study quality was evaluated using the Physiotherapy Evidence Database Scale.

This meta-analysis finally included 22 studies. Results revealed that exercise interventions effectively improved functional mobility as compared with that of the control group (SMD, -0.42; 95% CI, -0.61 to -0.24; P < .001). Exercise intervention characteristics (ie, weekly training frequency and session duration) and sample characteristic (ie, percentage of women) moderated the exercise-induced effects on this interesting outcome. Subgroup analyses showed intervention with low frequency (1-2 times/wk) (SMD, -0.71; 95% CI, -1.01 to -0.42; P < .001) had a larger improvement in mobility, followed by medium frequency (SMD, -0.33; 95% CI, -0.56 to -0.10; P < .01). In addition, interventions with a session duration of > 60 minutes (SMD, -0.60; 95% CI, -0.84 to -0.36; P < .001) and 45 to 60 minutes (SMD, -0.60; 95% CI, -0.91 to -0.29; P < .001) had a significant improvement in mobility. Moreover, exercise training had a significant improvement in mobility for studies with a high percentage of women (SMD, -0.49; 95% CI, -0.67 to -0.31; P < .001).

Exercise intervention is a promising way to improve functional mobility among older adults with cognitive impairment. Further evidence suggests that larger effects were observed in exercise intervention features of more than 45-minute session duration 1 to 3 times a week for at least 6 weeks regardless of exercise type. In addition, women benefit more from exercise interventions than men. Our study highlights that health care providers should prioritize integrating structured exercise programs into routine care for this population.

To evaluate the impact of resistance exercise on the risk of falls, fear of falling, muscle strength, neuropsychiatric symptoms and ability to perform activities of daily living in people with Alzheimer's disease (AD).

Single-blinded randomised controlled trial.

Five aged care centres specialising in AD, located in Andalucía, Spain.

Sixty people diagnosed with AD were assigned at random to either the intervention group (n = 30) or the control group (n = 30).

The intervention group completed three weekly resistance exercise sessions for 12 weeks, in addition to cognitive training, until completion of the study. The control group undertook cognitive training alone.

Main outcome measure: risk of falls (Short Physical Performance Battery).

muscle strength (hand dynamometry), neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire), fear of falling (Activities-Specific Balance Confidence Scale) and ability to perform activities of daily living (Lawton Instrumental Activities of Daily Living Scale).

The analysis demonstrated differences in favour of the intervention group, in both the short and medium term, for risk of falls [post-treatment: mean difference (MD) 1.5, 95% CI of the difference 0.9 to 2.0; 3-month follow up: MD 1.1, 95% CI of the difference 0.6 to 1.6]; fear of falling (post-treatment: MD 1.5, 95% CI of the difference 4.0 to 7.7; 3-month follow up: MD 6.3, 95% CI of the difference 4.3 to 8.2); activities of daily living (post-treatment: MD 0.2, 95% CI of the difference -0.01 to 0.4; 3-month follow up: MD 0.3, 95% CI of the difference 0.01 to 0.5); neuropsychiatric symptoms (post-treatment: MD -2.2, 95% CI of the difference -3.3 to -1.0; 3-month follow up: MD -2.4, 95% CI of the difference -3.7 to -1.2); and dynamometry (post-treatment: MD 3.1, 95% CI of the difference 2.5 to 3.7; 3-month follow up: MD 2.6, 95% CI of the difference 1.9 to 3.3).

Resistance exercise effectively reduces the risk of falls, fear of falling and neuropsychiatric symptoms, and improves muscle strength in people with AD in both the short and medium term. CONTRIBUTION OF THE PAPER.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which there is slow and gradual impairment of mental function. Considering the increase in cases due to population aging, the potential benefits of physical training in AD are of great importance and need further elucidation. This study aims to identify the impact of physical training on crucial aspects of AD such as cognitive status, physical performances, quality of life and activities of daily living. The bibliographic research was conducted according to the guidelines outlined in PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). After the selection process, 26 studies were included in the systematic review and meta-analysis. Physical training for up to 12 weeks had a moderate effect on the cognitive status (SMD: 0.34; 95 % CI: 0.07-0.61; p = 0.016), the physical performance (SMD: 0.75; 95 % CI: 0.43-1.06; p = 0.000) and the quality of life (SMD: 0.40; 95 % CI: 0.17-0.63; p = 0.567) of patients with AD, but did not affect their daily living activities (SMD: -0.10; 95 % CI: -0.31-0.12; p = 0.621). Physical training lasting from 16 to 24 weeks had a moderate effect only on the physical performance (SMD: 0.51; 95 % CI: 0.23-0.79; p = 0.000) of patients. Physical training for up to 12 weeks already leads to gains on the cognition, the physical performance and the quality of life of individuals with AD. Beyond the available evidence on health promotion resulting from physical training, guidelines should be established to define ideal training loads for patients with AD. Specific practical recommendations concerning the types, frequency, intensity or duration of physical exercise that may be the most efficient for ameliorating cognition, physical performance and quality of life of individuals with AD are still unclear.

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder and the leading cause of dementia worldwide, profoundly impacts health and quality of life. While cognitive impairments-such as memory loss, attention deficits, and disorientation-predominate in AD, motor symptoms, though common, remain underexplored. These motor symptoms, including gait disturbances, reduced cardiorespiratory fitness, muscle weakness, sarcopenia, and impaired balance, are often associated with advanced stages of AD and contribute to increased mortality. Emerging evidence, however, suggests that motor symptoms may be present in earlier stages and can serve as predictive markers for AD in older adults. Despite a limited understanding of the underlying mechanisms driving these motor symptoms, several key pathways have been identified, offering avenues for further investigation. This review provides an in-depth analysis of motor symptoms in AD, discussing its progression, potential mechanisms, and therapeutic strategies. Addressing motor symptoms alongside cognitive decline may enhance patient functionality, improve quality of life, and support more comprehensive disease management strategies.

Neurodegenerative diseases are global health challenges characterized by the progressive degeneration of nerve cells, leading to cognitive and motor impairments. The brain-gut-bone axis, a complex network that modulates multiple physiological systems, has gained increasing attention owing to its profound effects on the occurrence and development of neurodegenerative diseases. No comprehensive review has been conducted to clarify the triangular relationship involving the brain-gut-bone axis and its potential for innovative therapies for neurodegenerative disorders. In light of this, a new perspective is aimed to propose on the interplay between the brain, gut, and bone systems, highlighting the potential of their dynamic communication in neurodegenerative diseases, as they modulate multiple physiological systems, including the nervous, immune, endocrine, and metabolic systems. Therapeutic strategies for maintaining the balance of the axis, including brain health regulation, intestinal microbiota regulation, and improving skeletal health, are also explored. The intricate physiological interactions within the brain-gut-bone axis pose a challenge in the development of effective treatments that can comprehensively target this system. Furthermore, the safety of these treatments requires further evaluation. This review offers a novel insights and strategies for the prevention and treatment of neurodegenerative diseases, which have important implications for clinical practice and patient well-being.

Falls are the leading cause of injuries in older adults. Although it is well recognized that Alzheimer's disease (AD) increases the fall risk of older adults, the reported fall risk in people with AD varies drastically. The principal purpose of this study was to summarize and synthesize previous studies reporting fall risk-related metrics in people with AD.

This was a meta-analysis.

Thirty-one studies reporting relevant fall data among 4654 older adults with AD were included.

The fall prevalence, average number of falls, rate of recurrent fallers, and rate of injured fallers of included studies were meta-analyzed using random-effects models with inverse variance weights.

The pooled annual fall prevalence in older people with AD is 44.27% with an average annual number of falls of 1.30/person and a yearly rate of recurrent fallers of 42.08%. The reported rate of injured fallers was 45.0%.

Our results reinforce that people with AD experience a higher fall risk than their cognitively healthy counterparts. The pooled fall metrics in this meta-analysis extend our understanding of the fall risk in people with AD. In addition, standardized approaches are needed to report fall-related data for people with AD.

Falls are a primary cause of injuries and hospitalization in older adults. It has been reported that cognitive impairments and dementia can increase fall risk in the older population; however, it remains unknown if fall risk differs among subgroups of dementia. This meta-analysis summarized previous studies reporting the annual fall risk of people with Alzheimer's disease (AD) or mild cognitive impairment (MCI) and compared the fall risk between these two groups of people with dementia.

Thirty-five studies enrolling 7844 older adults with AD or MCI were included. The annual fall prevalence and average number of falls of the included studies were meta-analyzed and compared by random-effects models with inverse variance weights.

The annual fall prevalence in people with AD (43.55%) was significantly higher than MCI (35.26%, p < 0.001). A χ2 test indicated that the pooled fall prevalence is significantly higher in people with AD than MCI χ2 = 158.403, p < 0.001). Additionally, the yearly average number of falls in AD was higher than in MCI (1.30 vs 0.77 falls/person).

The results showed that older people with AD experience a higher annual fall prevalence with a larger number of falls than older adults with MCI. The results suggested that the fall risk measurements should be reported separately between people with AD and MCI. The findings could provide preliminary guidance for the identification of individuals with dementia who experience a high fall risk.

Extrinsic and intrinsic factors contribute to skin aging; nonetheless, they are intertwined. Moreover, intrinsic skin aging mirrors age-related declines in the entire human body's internal organs. There is evidence that skin appearance is an indicator of the general health of somebody or a visual certificate of health. Earlier, it was apparent that the intrinsic factors are unalterable, but the sparkling of skin aging gene therapy on the horizon is changing this narrative. Skin aging gene therapy offers tools for skin rejuvenation, natural beauty restoration, and therapy for diseases affecting the entire skin. However, skin aging gene therapy is an arduous and sophisticated task relying on precise interim stimulation of telomerase to extend telomeres and wend back the biological clock in the hopes to find the fountain of youth, while preserving cells innate biological features. Finding the hidden fountain of youth will be a remarkable discovery for promoting aesthetics medicine, genecosmetics, and healthy aging. Caloric restriction offers ultimate health benefits and a reproducible way to promote longevity in mammals, while delaying age-related diseases. Moreover, exercise further enhances these health benefits. This article highlights the potential of skin aging gene therapy and foretells the emerging dawn of the genecosmetics era.

To review the evidence for the effectiveness of multicomponent exercise (an exercise program combining aerobic, endurance, balance, and flexibility exercises) on cognition, physical function, and activities of daily living in people with dementia and mild cognitive impairment (MCI).

We conducted this study under the guidance of a designated protocol (PROSPERO CRD42022324641). Pertinent randomized controlled trials were selected from PubMed, Embase, Web of Science, and the Cochrane Library by 2 independent authors through May 2022.

Two authors independently extracted the data and assessed the quality of the included studies following the Cochrane Risk of Bias tool. Outcome data were extracted in a random effects model and estimated as Hedges' g and 95% confidence interval (CI). To validate specific results, the Egger test combined the Duval and Tweedie "trim and fill" method and sensitivity analysis with study removed were performed.

A total of 21 publications were eligible for the quantitative analysis. In dementia, estimates of Hedges' g showed effects on global cognition (g=0.403; 95% CI, 0.168-0.638; P<.05), especially executive function (g=0.344; 95% CI, 0.111-0.577; P<.05), flexibility (g=0.671; 95% CI, 0.353-0.989; P<.001), agility and mobility (g=0.402; 95% CI, 0.089-0.714; P<.05), muscle strength (g=1.132; 95% CI, 0.420-1.845; P<.05), and activities of daily living (g=0.402; 95% CI, 0.188-0.615; P<.05). Also, a positive trend was observed in gait speed. Additionally, multicomponent exercise had positive effects on global cognition (g=0.978; 95% CI, 0.298-1.659; P<.05) and executive function (g=0.448; 95% CI, 0.171-0.726; P<.05) in patients with MCI.

Our findings confirm the viability of multicomponent exercise as a management strategy for patients with dementia and MCI.

Alzheimer's disease (AD) is the main neurodegenerative disorder characterized by several pathophysiological features, including the misfolding of the tau protein and the amyloid beta (Aβ) peptide, neuroinflammation, oxidative stress, synaptic dysfunction, metabolic alterations, and cognitive impairment. These mechanisms collectively contribute to neurodegeneration, necessitating the exploration of therapeutic approaches with multiple targets. Physical exercise has emerged as a promising non-pharmacological intervention for AD, with demonstrated effects on promoting neurogenesis, activating neurotrophic factors, reducing Aβ aggregates, minimizing the formation of neurofibrillary tangles (NFTs), dampening inflammatory processes, mitigating oxidative stress, and improving the functionality of the neurovascular unit (NVU). Overall, the neuroprotective effects of exercise are not singular, but are multi-targets. Numerous studies have investigated physical exercise's potential in both AD patients and animal models, employing various exercise protocols to elucidate the underlying neurobiological mechanisms and effects. The objective of this review is to analyze the neurological therapeutic effects of these exercise protocols in animal models and compare them with studies conducted in AD patients. By translating findings from different approaches, this review aims to identify opportune, specific, and personalized therapeutic windows, thus advancing research on the use of physical exercise with AD patients.

To explore the effects of a multicomponent training (MT) physical exercise intervention in the cognitive function, neuropsychiatric symptoms, and quality of life of older adults with major neurocognitive disorder (NCD).

Quasi-experimental controlled trial. Thirty-six individuals (25 female) were equally distributed to an exercise group (aged 74.33 ± 5.87 years) or a control group (aged 81.83 ± 6.18 years). The Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog), the Neuropsychiatric Inventory (NPI) and the Quality of Life - Alzheimer's Disease (QoL-AD) tests were performed before and after the intervention.

There was no clear interaction effect factor of intervention on ADAS-Cog (B = 1.33, 95% CI: -2.61 - 5.28, P = .513), NPI (B = -8.35, 95% CI: -18.48 - 1.72, P = .115), and QoL-AD (B = 2.87, 95% CI: .01 - 5.73, P = .058).

The 6-month MT physical exercise intervention did not present evidence of slowing down cognitive decline neither improving neuropsychiatric symptomatology, and quality of life of older adults with major NCD. Future studies with larger samples are needed to better understand the impact of physical exercise interventions using MT methodology on specific cognitive abilities, neuropsychiatric symptoms, and quality of life domains.

Alzheimer's disease (AD) is a neurodegenerative disorder that is the major cause of dementia in the aged population. Recent researches indicate that patients with AD have a significantly increased fracture risk, but the pathological mechanisms are still unclear.

We systematically reviewed studies regarding bone fracture risk in AD to uncover links between the pathologies of osteoporosis and AD.

We searched the literature using the databases of PubMed, Web of Science, Embase and Cochrane Library. Studies were included if they evaluated bone fracture risk in AD patients and if they explored the pathogenesis and prevention of bone fractures in these patients.

AD patients had a significantly higher risk of bone fractures than age-matched controls. Multiple factors contributed to the increased risk of bone fractures in AD patients, including the direct effects of amyloid pathology on bone cells, abnormal brain-bone interconnection, Wnt/β-catenin signalling deficits, reduced activity, high risk of falls and frailty, and chronic immune activity. Exercise, prevention of falls and fortified nutrition were beneficial for reducing the fracture risk in AD patients. However, the efficacy of anti-osteoporotic agents in preventing bone fractures should be further evaluated in AD patients as corresponding clinical studies are very scarce.

Alzheimer's disease patients have increased bone fracture risk and decreased bone mineral density owing to multiple factors. Assessment of anti-osteoporotic agents' efficacy in preventing bone fractures of AD patients is urgently needed.

Growing evidence has demonstrated the benefits of regular exercise on cardiovascular, neural, and cognitive function in humans with Alzheimer's disease (AD). However, the consequences of AD on gastrointestinal morphology and the effects of regular exercise, which plays an important role against the development of certain gastrointestinal-related diseases, are still poorly understood. Therefore, to assess the changes in intestinal structure in a mouse model of AD and the impact of exercise, 2-month-old 3xTg-AD male mice were subjected to treadmill running 5 days per week for a period of 5 months. Jejunum from 3xTg-AD mice analyzed by histochemical methods revealed significant alterations in morphology. Compared to age-matched wild-type (WT) mice, villi length and crypt depth were increased, and collagen content of jejunum was elevated in 3xTg-AD mice. Jejunum wall dimensions, expressed as total wall thickness, outer longitudinal thickness, and inner circular thickness were decreased in 3xTg-AD compared to WT. Smooth muscle actin expression in jejunal wall was decreased in 3xTg-AD. Most of these aberrations were improved with exercise. Western blot expression of cyclin dependent kinase 5 (CDK5, involved in neural cell death and hyperphosphorylation of tau), was elevated in 3xTg-AD jejunum. This was associated with a 4-fold increase in tau5 expression. Exercise prevented the increase in expression of CDK5 and tau5. Expression of caspase 3 (an apoptotic marker) was elevated in 3xTg-AD jejunum and exercise prevented this. The results of our study indicate that the abnormalities in jejunum of the 3xTg mouse model of AD were prevented with exercise training.

Physical activity interventions can alleviate the course of disease for individuals with dementia (IWD) who have been extraordinarily affected by the COVID-19 pandemic. Information and Communication Technology (ICT) provides new opportunities not only to mitigate negative effects of the pandemic but also to sustainably improve everyday life of IWD in nursing homes. The aim of the present study was to evaluate the ICT-based InCoPE-App, which was used to assess physical and cognitive performance and deliver individualized exercise for IWD, with regard to 1) user experience of nursing assistants, and 2) trends toward the effectiveness of the intervention on physical and cognitive performance of IWD. An 18-week individualized multidomain intervention (2 × 60 min/session) was delivered to an intervention group (IG; n = 10, mean age 88.4 ± 5.6, 70% female) by nursing assistants (n = 10, mean age 56.1 ± 10.4, 90% female) using the InCoPE-App. A control group (CG; n = 3, mean age 87.3 ± 3.5, 100% female) received conventional treatment. User experience was assessed among nursing assistants by different questionnaires, i.e., PSSUQ and ISONORM 9241/110-S for usability, and AttrakDiff2 for pragmatic (PQ), hedonic quality-identity and stimulation (HQI and HQS), and attractiveness (ATT). Trends toward the effectiveness of the intervention were assessed using MMSE (global cognitive function), FICSIT-4 (balance), 6MWT and TUG (mobility), and m30CST (function of lower limbs). Usability of the InCoPE-App was rated as high by nursing assistants (mean ± SD; overall PSSUQ 2.11 ± 0.75; overall ISONORM 9241/110-S 1.90 ± 0.88; ATT 1.86 ± 1.01; PQ 1.79 ± 1.03; HQI 1.8 ± 0.79; and HQS 1.37 ± 0.69). Dropout was high in the total sample (36.7%). Trends toward the effectiveness were observed within IG in nine IWD who showed positive or neutral trends in at least two physical performance outcomes. Seven participants had positive or neutral trends in the FICSIT-4, seven participants in m30CST, and four and seven participants in 6MWT and TUG, respectively. In conclusion, the InCoPE-App has good nursing assistant-rated usability, whereas training effects and intervention adherence were rather low most likely due to COVID-19 restrictions. Single-subject research revealed more positive than negative trends in IG of IWD. Further research is needed to evaluate feasibility, suitability, and effectiveness of the InCoPE-App.

To examine the effects of a 6-month multicomponent (MT) exercise intervention in the functional capacity and ability to independently perform activities of daily living (ADL) of individuals diagnosed with neurocognitive disorder (NCD).

A quasi-experimental controlled trial with a parallel design study was conducted in multicentered community-based settings. Forty-three individuals (N Female: 30) were allocated to an exercise group (EG; N: 23; mean 75.09, SD = 5.54 years) or a control group (CG; N:20; mean 81.90, SD = 1.33 years). The EG engaged in a 6-month MT program (60-min sessions, twice a week). Exercise sessions were divided into a warm-up, specific training (e.g., coordination and balance, lower and upper body strength, and aerobics), and cool down. Lower body function, mobility, and gait speed were evaluated through Short Physical Performance Battery (SPPB), Timed-Up and Go test (TUG) and 6-Meter Walk test, respectively. The Barthel Index (BI) was administered to assess individuals' ADL independence. Evaluations were performed before and after the 6-month intervention.

Linear Mixed Models revealed a statistically significant interaction (time X group) effect factor on SPPB (B = 2.33, 95% CI: 1.39-3.28, p < 0.001), TUG (B = - 11.15, 95% CI: - 17.23 - - 5.06, p = 0.001), and 6-Meter Walk test (B = 0.17, 95% CI: 0.08-0.25, p < 0.001). No differences between groups or assessment moments were found in the ability of individuals to independently perform ADL.

The 6-month MT exercise intervention improves the functional capacity of older adults living with NCD.

ClinicalTrials.gov - identifier number NCT04095962 ; retrospectively registered on 19 September 2019.

Alzheimer's disease (AD) is a major cause of dementia in older adults and is fast becoming a major societal and economic burden due to an increase in life expectancy. Age seems to be the major factor driving AD, and currently, only symptomatic treatments are available. AD has a complex etiology, although mitochondrial dysfunction, oxidative stress, inflammation, and metabolic abnormalities have been widely and deeply investigated as plausible mechanisms for its neuropathology. Aβ plaques and hyperphosphorylated tau aggregates, along with cognitive deficits and behavioral problems, are the hallmarks of the disease. Restoration of mitochondrial bioenergetics, prevention of oxidative stress, and diet and exercise seem to be effective in reducing Aβ and in ameliorating learning and memory problems. Many mitochondria-targeted antioxidants have been tested in AD and are currently in development. However, larger streamlined clinical studies are needed to provide hard evidence of benefits in AD. This review discusses the causative factors, as well as potential therapeutics employed in the treatment of AD.