Cognitive dysfunction and multiple sclerosis: developing a rationale for considering the efficacy of exercise training

Cognitive impairment is a prevalent, disabling, and poorly managed consequence of multiple sclerosis (MS). This underscores the importance of considering alternative approaches, such as exercise training, for managing cognitive impairment in persons with MS. The consideration of exercise training is warranted based on evidence summarized in literature reviews and meta-analyses that (1) aerobic fitness, physical activity, and exercise training are associated with better cognitive function in older adults; and (2) exercise training has comparable effects on mobility and quality of life outcomes in older adults and persons with MS. To date, research examining aerobic fitness, physical activity, and exercise training effects on cognition in MS is nascent and mostly includes cross-sectional designs that provide preliminary evidence for a well-designed randomized controlled trial (RCT). We believe that a future RCT should adopt research methodologies and practices from gerontology when examining exercise training and cognition in MS. This will maximize the potential for successfully generating a body of knowledge on exercise training and cognition with the potential for impacting the lives of persons with MS.     

Feasibility and perception of the impact from aerobic exercise in older adults with Alzheimer's disease

Background: The subjective experience of participating in aerobic exercise is unknown in Alzheimer's disease (AD). Objective: The purpose of this study was to understand the subjective perceptions of the feasibility and impact of a 6-month, moderate-intensity aerobic exercise intervention by older adults with AD and their family caregivers. Methods: Ten older adults with AD who completed the intervention and their family caregivers participated in four focus group interviews. Results: Four converging themes were identified: "There was no perceived positive change in cognitive symptoms," "The 6-month exercise program was socially rewarding," "The 6-month exercise program increased physical strength," and "Participation in aerobic exercise was a positive experience." Family caregivers further identified two additional themes: "The exercise program led to improved attitude in older adults with AD" and "The exercise program reduced caregiver stress." Discussion: Aerobic exercise is a feasible and well-perceived intervention for older adults with AD and their family caregivers.     

The functions of the orbitofrontal cortex

Parkinson's disease is commonly accompanied by cognitive issues that limit participation in activities of daily living. Unfortunately, most current treatment paradigms and pharmacotherapeutics fail to address the cognitive impairment demonstrated in this population. Mounting evidence in healthy older adults suggests that aerobic exercise may improve cognitive function. This article describes a patient with Parkinson's disease prescribed 8 weeks of aerobic exercise. Despite very high performance at baseline, the participant improved on several cognitive measures post exercise. The results of this investigation mimic the research in healthy older adults. We therefore suggest that future large scale randomized trials are warranted to evaluate the efficacy of aerobic exercise for ameliorating declines in cognitive performance in persons with PD.     

Benefits of exercise training on cerebrovascular and cognitive function in ageing

Derangements in cerebrovascular structure and function can impair cognitive performance throughout ageing and in cardiometabolic disease states, thus increasing dementia risk. Modifiable lifestyle factors that cause a decline in cardiometabolic health, such as physical inactivity, exacerbate these changes beyond those that are associated with normal ageing. The purpose of this review was to examine cerebrovascular, cognitive and neuroanatomical adaptations to ageing and the potential benefits of exercise training on these outcomes in adults 50 years or older. We systematically searched for cross-sectional or intervention studies that included exercise (aerobic, resistance or multimodal) and its effect on cerebrovascular function, cognition and neuroanatomical adaptations in this age demographic. The included studies were tabulated and described narratively. Aerobic exercise training was the predominant focus of the studies identified; there were limited studies exploring the effects of resistance exercise training and multimodal training on cerebrovascular function and cognition. Collectively, the evidence indicated that exercise can improve cerebrovascular function, cognition and neuroplasticity through areas of the brain associated with executive function and memory in adults 50 years or older, irrespective of their health status. However, more research is required to ascertain the mechanisms of action.     

Structured exercise does not stabilize cognitive function in individuals with mild cognitive impairment residing in a structured living facility

Exercise has been shown to have positive effects on the brain and cognition in healthy older adults, though no study has directly examined possible cognitive benefits of formal exercise programs in persons with mild cognitive impairment (MCI) living in structured facilities. Thirty-one participants completed neuropsychological testing and measures of cardiovascular fitness at baseline and after 6 months of a structured exercise program that included aerobic and resistance training. While exercise improved cardiovascular fitness in persons with MCI, there was no improvement in cognitive function. Rather, MCI patients in this sample declined in performance on several tests sensitive to Alzheimer's disease. Examined in the context of past work, it appears exercise may be beneficial prior to the onset of MCI, though less helpful after its onset.     

Student-led exercise sessions yield significant fitness gains for Alzheimer's patients

At a time when they are losing skills in virtually all arenas of life, persons with Alzheimer's disease can experience significant, esteem-building achievements in physical fitness and mood through supervised participation in an exercise program. The effects of physical exercise plus cognitive and social stimulation on persons with early stage Alzheimer's disease were assessed in a longitudinal study. Twenty-four such individuals, aged 54 to 88 at program entry, participated in 16 to 20 exercise sessions and 10 community activity sessions per semester for two to eight semesters. Half of the weekly exercise sessions included memory and language stimulation activities. Students, supplemented by family caregivers, supervised the sessions. Exercise sessions consisted of flexibility, balance, aerobic, and weight resistance activities. Preparticipation and semiannual post-testing of aerobic fitness and duration and upper and lower body strength was done. Highly significant fitness gains (p < .001) were achieved in the six-minute walk test, upper and lower body strength, and duration of aerobic exercise. Five participants, aged 86 to 91, completed six to eight semesters and were doing 27 to 45 minutes of aerobics per session at program's end. Five participants scored within the normal range for age-matched healthy active adults on the six-minute walk test at baseline. Nine others achieved and three exceeded the normal range during treatment. Cognitive decline was slowed and mood improved. First-year cognitive outcomes have been published elsewhere. An article reporting final cognitive outcomes is in preparation; Outcome data is summarized on the project website: www.u.arizona.edu/ ~sarkin/elderrehab.html. The benefits of physical exercise can be made available at nominal cost to Alzheimer's patients and other elderly persons by using students to provide transportation, supervision, and the motivational support that is key to exercise adherence. Further research is needed to determine the relative contributions of each program component to the positive outcomes.     

The Therapeutic Potential of Exercise to Improve Mood,Cognition, and Sleep in Parkinson's Disease

In addition to the classic motor symptoms, Parkinson's disease (PD) is associated with a variety of nonmotor symptoms that significantly reduce quality of life, even in the early stages of the disease. There is an urgent need to develop evidence‐based treatments for these symptoms, which include mood disturbances, cognitive dysfunction, and sleep disruption. We focus here on exercise interventions, which have been used to improve mood, cognition, and sleep in healthy older adults and clinical populations, but to date have primarily targeted motor symptoms in PD. We synthesize the existing literature on the benefits of aerobic exercise and strength training on mood, sleep, and cognition as demonstrated in healthy older adults and adults with PD, and suggest that these types of exercise offer a feasible and promising adjunct treatment for mood, cognition, and sleep difficulties in PD. Across stages of the disease, exercise interventions represent a treatment strategy with the unique ability to improve a range of nonmotor symptoms while also alleviating the classic motor symptoms of the disease. Future research in PD should include nonmotor outcomes in exercise trials with the goal of developing evidence‐based exercise interventions as a safe, broad‐spectrum treatment approach to improve mood, cognition, and sleep for individuals with PD. © 2015 International Parkinson and Movement Disorder Society     

The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: Results of a one‐year exercise intervention

Cerebral white matter (WM) degeneration occurs with increasing age and is associated with declining cognitive function. Research has shown that cardiorespiratory fitness and exercise are effective as protective, even restorative, agents against cognitive and neurobiological impairments in older adults. In this study, we investigated whether the beneficial impact of aerobic fitness would extend to WM integrity in the context of a one‐year exercise intervention. Further, we examined the pattern of diffusivity changes to better understand the underlying biological mechanisms. Finally, we assessed whether training‐induced changes in WM integrity would be associated with improvements in cognitive performance independent of aerobic fitness gains. Results showed that aerobic fitness training did not affect group‐level change in WM integrity, executive function, or short‐term memory, but that greater aerobic fitness derived from the walking program was associated with greater change in WM integrity in the frontal and temporal lobes, and greater improvement in short‐term memory. Increases in WM integrity, however, were not associated with short‐term memory improvement, independent of fitness improvements. Therefore, while not all findings are consistent with previous research, we provide novel evidence for correlated change in training‐induced aerobic fitness, WM integrity, and cognition among healthy older adults. Hum Brain Mapp 34:2972–2985, 2013. © 2012 Wiley Periodicals, Inc.     

Hallucinations in Older Adults: A Practical Review

Older adults experience hallucinations in a variety of social, physical, and mental health contexts. Not everyone is open about these experiences, as hallucinations are surrounded with stigma. Hence, hallucinatory experiences in older individuals are often under-recognized. They are also commonly misunderstood by service providers, suggesting that there is significant scope for improvement in the training and practice of professionals working with this age group. The aim of the present article is to increase knowledge about hallucinations in older adults and provide a practical resource for the health and aged-care workforce. Specifically, we provide a concise narrative review and critique of (1) workforce competency and training issues, (2) assessment tools, and (3) current treatments and management guidelines. We conclude with a brief summary including suggestions for service and training providers and future research.     

Weight loss in adults with Down syndrome and with dementia in Alzheimer's disease

An association between weight loss and Alzheimer's disease has been established in the general population but little information is available regarding this association in people with intellectual disabilities. A 4-year longitudinal study of adults with Down syndrome with and without Alzheimer's disease was undertaken. Age-associated weight loss was seen in virtually all older adults with Down syndrome. A significant association between weight loss and Alzheimer's disease was found for older adults with Down syndrome. This study highlights important research and clinical issues regarding weight loss and nutrition in Down syndrome adults with dementia.     

Exercise,Fitness, and Neurocognitive Function in Older Adults: The “Selective Improvement” and “Cardiovascular Fitness” Hypotheses

Background   Although basic research has uncovered biological mechanisms by which exercise could maintain and enhance adult brain health, experimental human studies with older adults have produced equivocal results. Purpose   This randomized clinical trial aimed to investigate the hypotheses that (a) the effects of exercise training on the performance of neurocognitive tasks in older adults is selective, influencing mainly tasks with a substantial executive control component and (b) performance in neurocognitive tasks is related to cardiorespiratory fitness. Methods   Fifty-seven older adults (65–79 years) participated in aerobic or strength-and-flexibility exercise training for 10 months. Neurocognitive tasks were selected to reflect a range from little (e.g., simple reaction time) to substantial (i.e., Stroop Word–Color conflict) executive control. Results   Performance in tasks requiring little executive control was unaffected by participating in aerobic exercise. Improvements in Stroop Word–Color task performance were found only for the aerobic exercise group. Changes in aerobic fitness were unrelated to changes in neurocognitive function. Conclusions   Aerobic exercise in older adults can have a beneficial effect on the performance of speeded tasks that rely heavily on executive control. Improvements in aerobic fitness do not appear to be a prerequisite for this beneficial effect.

The benefits of exercise training in multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelination and neurodegeneration within the CNS. This damage of CNS structures leads to deficits of body functions, which, in turn, affect patient activities, such as walking, and participation. The pathogenesis and resulting consequences of MS have been described as concepts within the International Classification of Functioning, Disability and Health (ICF) model-an international standard to describe and measure health and disability. Evidence suggests that exercise training in people with MS has the potential to target and improve many of the components outlined in the ICF model. Although the body of research examining the effects of exercise training on depression, cognition and participatory outcomes is not sufficiently developed, some preliminary evidence is promising. Exercise training is proposed to affect inflammation, neurodegeneration, and CNS structures, but current evidence is limited. In this Review, we discuss evidence from clinical trials that suggests beneficial effects of exercise training on muscle strength, aerobic capacity and walking performance, and on fatigue, gait, balance and quality of life. Issues with current studies and areas of future research are highlighted.     

Comparison of depressive symptoms between homebound older adults and ambulatory older adults

Due to the social isolation imposed by chronic illness and functional limitations, homebound older adults are more vulnerable to depression than their mobility-unimpaired peers. In this study, we compared 81 low-income homebound older adults, aged 60 and older, with their 130 ambulatory peers who attended senior centers, with respect to their depressive symptoms, depression risk and protective factors, and self-reported coping strategies. Even controlling for sociodemographics, health problems, and other life stressors, being homebound, as opposed to participating in senior centers, was significantly associated with higher depressive symptoms. However, when the coping resources-social support and engagement in frequent physical exercise, in particular-were added to the regression model, the homebound state was no longer a significant factor, showing that the coping resources buffered the effect of the homebound state on depressive symptoms. In terms of self-reported coping strategies, even among the depressed respondents, only a small proportion sought professional help, and that was largely limited to consulting their regular physician and social workers, who may not have had professional training in mental health interventions.     

Longitudinal functional connectivity changes correlate with mood improvement after regular exercise in a dose‐dependent fashion

Exercise increases wellbeing and improves mood. It is however unclear how these mood changes relate to brain function. We conducted a randomized controlled trial investigating resting‐state modifications in healthy adults after an extended period of aerobic physical exercise and their relationship with mood improvements. We aimed to identify novel functional networks whose activity could provide a physiological counterpart to the mood‐related benefits of exercise. Thirty‐eight healthy sedentary volunteers were randomised to either the aerobic exercise group of the study or a control group. Participants in the exercise group attended aerobic sessions with a physiotherapist twice a week for 16 weeks. Resting‐state modifications using magnetic resonance imaging were assessed before and after the programme and related to mood changes. An unbiased approach using graph metrics and network‐based statistics was adopted. Exercise reduced mood disturbance and improved emotional wellbeing. It also induced a decrease in local efficiency in the parahippocampal lobe through strengthening of the functional connections from this structure to the supramarginal gyrus, precentral area, superior temporal gyrus and temporal pole. Changes in mood disturbance following exercise were correlated with those in connectivity between parahippocampal gyrus and superior temporal gyrus as well as with the amount of training. No changes were detected in the control group. In conclusion, connectivity from the parahippocampal gyrus to motor, sensory integration and mood regulation areas was strengthened through exercise. These functional changes might be related to the benefits of regular physical activity on mood.     

Current Perspectives on Aerobic Exercise in People with Parkinson’s Disease

Parkinson’s disease (PD) is a progressive neurological disorder characterized by motor and non-motor symptoms for which only symptomatic treatments exist. Exercise is a widely studied complementary treatment option. Aerobic exercise, defined as continuous movement of the body’s large muscles in a rhythmic manner for a sustained period that increases caloric requirements and aims at maintaining or improving physical fitness, appears promising. We performed both a scoping review and a systematic review on the generic and disease-specific health benefits of aerobic exercise for people with PD. We support this by a meta-analysis on the effects on physical fitness (VO₂max), motor symptoms (Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor section), and health-related quality of life (39-item Parkinson’s disease Questionnaire (PDQ-39)). Aerobic exercise has generic health benefits for people with PD, including a reduced incidence of cardiovascular disease, a lower mortality, and an improved bone health. Additionally, there is level 1 evidence that aerobic exercise improves physical fitness (VO₂max) and attenuates motor symptoms (MDS-UPDRS motor section) in the off-medication state, although the long-term effects (beyond 6 months) remain unclear. Dosing the exercise matters: improvements appear to be greater after training at higher intensities compared with moderate intensities. We found insufficient evidence for a beneficial effect of aerobic exercise on health-related quality of life (PDQ-39) and conflicting results regarding non-motor symptoms. Compliance to exercise regimes is challenging for PD patients but may be improved by adding exergaming elements to the training program. Aerobic exercise seems a safe intervention for people with PD, although care must be taken to avoid falls in at-risk individuals. Further studies are needed to establish the long term of aerobic exercise, including a focus on non-motor symptoms and health-related quality of life.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00904-8) contains supplementary material, which is available to authorized users.Key Words: Exercise, Parkinson’s disease, endurance training, locomotion, health-related quality of life, mobility limitation     

beta-Amyloid is associated with reduced cognitive function in healthy older adults

Though elevated beta-amyloid deposition is associated with Alzheimer's disease, recent evidence suggests beta-amyloid is elevated in healthy older adults prior to the onset of Alzheimer's disease. No study has yet investigated whether reduced cognitive function is related to beta-amyloid elevation in healthy older adults. Thirty-five healthy older adults underwent neuropsychological testing and fasting blood draw with subsequent serum beta-amyloid 1-40 level quantification. beta-amyloid was negatively correlated with several aspects of cognition. Findings indicate that beta-amyloid level is associated with cognitive function in healthy older adults in a pattern similar to early Alzheimer's disease. Further work investigating possible mechanisms is needed.     

Elaborated spaced-retrieval and prospective memory in mild Alzheimer's disease

Prospective memory, or the timely remembering of a planned action, is conceptualised as a cognitive process demanding episodic memory and executive attention. Impairments in these skills are characteristic of the cognitive decline in early Alzheimer's disease, providing an expectation of prominent prospective memory difficulties in this population, and yet surprisingly, memory performance in early Alzheimer's disease has rarely been evaluated within a prospective memory framework. In a preliminary study we demonstrated that older adults with early Alzheimer's disease (n=14), as compared to healthy older adults (n=14), were significantly impaired in a simple experimental paradigm of prospective remembering (a text-reading task). In a subsequent intervention study, we investigated the efficacy of spaced-retrieval for improving the prospective remembering performance of older adults with early Alzheimer's disease (n=16) compared to healthy older adults (n=16) under two learning conditions: a spaced-retrieval technique alone or spaced-retrieval combined with elaborated encoding of task. The majority of the Alzheimer's disease group (63%) demonstrated benefit in prospective remembering in the combined condition as compared to spaced-retrieval alone. Participants with Alzheimer's disease who demonstrated better executive attention (Trail Making- set-shifting) and/or better retrospective memory (Hopkins Verbal Learning Test-Revised- recognition) were more successful in the combined learning condition.     

Effect of physical exercise on seizure occurrence in a model of temporal lobe epilepsy in rats.

Although the favorable effect of physical fitness on general health is unquestionable, physical exercise and fitness programs in patients with epilepsy are still a matter of controversy. Little objective evidence regarding the effect of exercise on seizure frequency and severity has been reported. One sought to clarify the relationship between exercise and epilepsy in an animal model of temporal lobe epilepsy (the pilocarpine model of epilepsy). To evaluate the effect of an aerobic physical program on seizure frequency, 29 epileptic animals were continuously monitored during 24 h for 135 days after the first spontaneous recurrent seizure (SRS) and divided into three groups. The first group (N = 14) was submitted to an aerobic exercise program (training group). The second group (N = 7) was maintained in the treadmill for the same time as the training group without being submitted to physical exercise (sham group). The third group (N = 8) served as control. The behavioral observation was divided in three periods of 45 days. The first period was used to determine the number of seizures before physical training program. The second period was utilized to determine the number of seizures during the physical training program. The third period was used to analyze the frequency of seizures after the physical training program. The mean frequency of seizures in the control and sham groups increased significantly from period 1 to period 2 and from period 1 to period 3. However, in the training group, the frequency of seizures did not change significantly between the three periods of 45 days of observation. When the same periods of the three groups were analyzed together, a significant reduction in seizure frequency was observed comparing the training group with the control and sham groups during the period of physical training. The data presented in this study suggest that physical exercise is not a seizure-inducing factor in this experimental model of epilepsy.     

Impact of exercise on older adults’ mood is moderated by sleep and mediated by altered brain connectivity

Older adults comprise the fastest growing global demographic and are at increased risk of poor mental health outcomes. Although aerobic exercise and sleep are critical to the preservation of emotional well-being, few studies have examined their combined mood-enhancing effects, or the potential neural mechanisms underlying these effects. Here, we used a randomized crossover design to test the impact of acute exercise on mood and the intrinsic functional connectivity (iFC) of the cingulo-opercular network in physically healthy older adults. Wrist actigraphy provided objective indices of sleep. Results revealed that 30 min of moderate-intensity aerobic exercise acutely enhanced positive affect (PA) and reduced iFC between the cingulo-opercular network and the hippocampus. Both effects were magnified among older adults with greater sleep disturbance. Exercise-induced changes in hippocampal iFC mediated relations between sleep disturbance and exercise-induced increases in PA. These findings provide evidence that aerobic exercise enhances mood, that it does so by altering connectivity between the anterior insula—a key hub in the cingulo-opercular network—and the hippocampus and that lower sleep quality is a stronger predictor of these effects among older adults. These observations underscore the benefits of moderate-intensity exercise—a safe and scalable behavioral intervention—and provide new clues about the neural circuitry underlying the interactive effects of sleep and exercise on mood.     

A Future Research Agenda for Digital Geriatric Mental Healthcare

The proliferation of mobile, online, and remote monitoring technologies in digital geriatric mental health has the potential to lead to the next major breakthrough in mental health treatments. Unlike traditional mental health services, digital geriatric mental health has the benefit of serving a large number of older adults, and in many instances, does not rely on mental health clinics to offer real-time interventions. As technology increasingly becomes essential in the everyday lives of older adults with mental health conditions, these technologies will provide a fundamental service delivery strategy to support older adults’ mental health recovery. Although ample research on digital geriatric mental health is available, fundamental gaps in the scientific literature still exist. To begin to address these gaps, we propose the following recommendations for a future research agenda: 1) additional proof-of-concept studies are needed; 2) integrating engineering principles in methodologically rigorous research may help science keep pace with technology; 3) studies are needed that identify implementation issues; 4) inclusivity of people with a lived experience of a mental health condition can offer valuable perspectives and new insights; and 5) formation of a workgroup specific for digital geriatric mental health to set standards and principles for research and practice. We propose prioritizing the advancement of digital geriatric mental health research in several areas that are of great public health significance, including 1) simultaneous and integrated treatment of physical health and mental health conditions; 2) effectiveness studies that explore diagnostics and treatment of social determinants of health such as “social isolation” and “loneliness;” and 3) tailoring the development and testing of innovative strategies to minority older adult populations.