Exercise Model Research Articles

Advancing Alzheimer's Therapeutics: Exploring the Impact of Physical Exercise in Animal Models and Patients.

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.

Comparing exercise determinants between Black and White older adults with heart failure

BackgroundHeart Failure is a leading cause of mortality among older adults. Engaging in regular exercise at moderate-to-vigorous intensity has been shown to improve survival rates. Theory-informed methodologies have been recommended to promote exercise, but limited application of theoretical framework has been conducted for understanding racial disparities among older adults with heart failure. This study aimed to use the Health Belief Model to compare exercise behavior determinants between Black and White older adults diagnosed with heart failure.MethodsThe HF-ACTION Trial is a multi-site study designed to promote exercise among individuals with heart failure that randomized participants to an experimental (three months of group exercise sessions followed by home-based training) or control arm. The present study used structural equation modeling to test the change in Health Belief Model constructs and exercise behavior across 12 months among older adults.ResultsParticipants (n = 671) were older adults, 72.28 (SD = 5.41) years old, (Black: n = 230; White, n = 441) diagnosed with heart failure and reduced ejection fraction. The model found perceived benefits, self-efficacy, perceived threats, and perceived barriers to predict exercise behavior among Black and White older adults. However, among these constructs, only perceived benefits and self-efficacy were facilitated via intervention for both races. Additionally, the intervention was effective for addressing perceived barriers to exercise only among White participants. Finally, the intervention did not result in a change of perceived threats for both races.ConclusionsAmong health belief model constructs, perceived threats and barriers were not facilitated for both races in the experimental arm, and the intervention did not resolve barriers among Black older adults. Racial differences need to be considered when designing interventions for clinical populations as future studies are warranted to address barriers to exercise among Black older adults with heart failure.

Corrigendum: Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer's disease.

Corrigendum: Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer's disease.

Aerobic Exercise Ameliorates Muscle Atrophy Induced by Methylglyoxal via Increasing Gastrocnemius and Extensor Digitorum Longus Muscle Sensitivity.

Muscle atrophy is characterized by the loss of muscle function. Many efforts are being made to prevent muscle atrophy, and exercise is an important alternative. Methylglyoxal is a well-known causative agent of metabolic diseases and diabetic complications. This study aimed to evaluate whether methylglyoxal induces muscle atrophy and to evaluate the ameliorative effect of moderate-intensity aerobic exercise in a methylglyoxal-induced muscle atrophy animal model. Each mouse was randomly divided into three groups: control, methylglyoxal-treated, and methylglyoxal-treated within aerobic exercise. In the exercise group, each mouse was trained on a treadmill for 2 weeks. On the last day, all groups were evaluated for several atrophic behaviors and skeletal muscles, including the soleus, plantaris, gastrocnemius, and extensor digitorum longus were analyzed. In the exercise group, muscle mass was restored, causing in attenuation of muscle atrophy. The gastrocnemius and extensor digitorum longus muscles showed improved fiber cross-sectional area and reduced myofibrils. Further, they produced regulated atrophy-related proteins (i.e., muscle atrophy F-box, muscle RING-finger protein-1, and myosin heavy chain), indicating that aerobic exercise stimulated their muscle sensitivity to reverse skeletal muscle atrophy. In conclusion, shortness of the gastrocnemius caused by methylglyoxal may induce the dynamic imbalance of skeletal muscle atrophy, thus methylglyoxal may be a key target for treating skeletal muscle atrophy. To this end, aerobic exercise may be a powerful tool for regulating methylglyoxal-induced skeletal muscle atrophy.

Exercise promotes growth and rescues volume deficits in the hippocampus after cranial radiation in young mice.

Human and animal studies suggest that exercise promotes healthy brain development and function, including promoting hippocampal growth. Childhood cancer survivors that have received cranial radiotherapy exhibit hippocampal volume deficits and are at risk of impaired cognitive function, thus they may benefit from regular exercise. While morphological changes induced by exercise have been characterized using magnetic resonance imaging (MRI) in humans and animal models, evaluation of changes across the brain through development and following cranial radiation is lacking. In this study, we used high-resolution longitudinal MRI through development to evaluate the effects of exercise in a pediatric mouse model of cranial radiation. Female mice received whole-brain radiation (7 Gy) or sham radiation (0 Gy) at an infant equivalent age (P16). One week after irradiation, mice were housed in either a regular cage or a cage equipped with a running wheel. In vivo MRI was performed prior to irradiation, and at three subsequent timepoints to evaluate the effects of radiation and exercise. We used a linear mixed-effects model to assess volumetric and cortical thickness changes. Exercise caused substantial increases in the volumes of certain brain regions, notably the hippocampus in both irradiated and nonirradiated mice. Volume increases exceeded the deficits induced by cranial irradiation. The effect of exercise and irradiation on subregional hippocampal volumes was also characterized. In addition, we characterized cortical thickness changes across development and found that it peaked between P23 and P43, depending on the region. Exercise also induced regional alterations in cortical thickness after 3 weeks of voluntary exercise, while irradiation did not substantially alter cortical thickness. Our results show that exercise has the potential to alter neuroanatomical outcomes in both irradiated and nonirradiated mice. This supports ongoing research exploring exercise as a strategy for improving neurocognitive development for children, particularly those treated with cranial radiotherapy.

Exercise intensity and sex alter neurometabolic, transcriptional, and functional recovery following traumatic brain injury

Physical exercise represents a potentially inexpensive, accessible, and optimizable rehabilitation approach to traumatic brain injury (TBI) recovery. However, little is known about the impact of post-injury exercise on the neurometabolic, transcriptional, and cognitive outcomes following a TBI. In the current study, we examined TBI outcomes in adolescent male and female mice following a controlled cortical impact (CCI) injury. Mice underwent a 10-day regimen of sedentary, low-, moderate-, or high-intensity treadmill exercise and were assessed for cognitive function, histopathology, mitochondrial function, and oxidative stress. Among male mice, low-moderate exercise improved cognitive recovery, and reduced cortical lesion volume and oxidative stress, whereas high-intensity exercise impaired both cognitive recovery and mitochondrial function. On the other hand, among female mice, exercise had an intermediate effect on cognitive recovery but significantly improved brain mitochondrial function. Moreover, single nuclei RNA sequencing of perilesional brain tissue revealed neuronal plasticity-related differential gene expression that was largely limited to the low-intensity exercise injured males. Taken together, these data build on previous reports of the neuroprotective capacity of exercise in a TBI model, and reveal that this rehabilitation strategy impacts neurometabolic, functional, and transcriptional outcome measures in an intensity- and sex-dependent manner.

The long-term exercise after traumatic brain injury: Reharmonizing brain by sound body

Traumatic brain injuries (TBI) refer to multiple acquired dysfunctions arising from damage to the brain caused by an external force, including rapid acceleration/deceleration and concussion. Among them, mild TBI (mTBI) accounts for most cases (up to 90%) of injuries. It is responsible for a variety of symptoms, including anxiety, depression, and cognitive impairments that remain difficult to be treated. It has been reported that regular physical activity, as well as, improving life quality, display a neuroprotective function, suggesting a possible role in post-traumatic rehabilitation.In this study, we investigated the effects of treadmill exercise in a mice mTBI model by behavioural, electrophysiological and neurochemical analysis.Daily exercise decreased anxiety, aggressive behavior, and depression in mTBI mice. Accordingly, electrophysiological and neurochemical maladaptive rearrangement occurring in the hippocampus of mTBI mice were prevented by the exercise.

Enhanced Aggregate Framework to Model Crash Frequency by Accommodating Zero Crashes by Crash Type

In recent years, joint count and fractional split model structure based approaches have emerged as a credible alternative for multivariate crash frequency dependent variables. However, current approaches in the fractional split theme have a limitation. The fractional split component of these frameworks allocates a proportion to all crash configurations. It is possible that, across spatial units, several crash configurations might have a large share of zero crashes. In the traditional multivariate context, in the presence of a high share of zeros, researchers employ zero-inflated or hurdle variants such as the zero inflated negative binomial model. The current research effort improves the fractional split based multivariate model systems with an explicit consideration for the potential presence of zeros by crash configuration. The newly included binary component can be employed to identify safer (or riskier) zones by crash configuration. The framework also accommodates unobserved heterogeneity across the components of the model system. The proposed model structure is estimated using zonal data from the Central Florida region, U.S., for 2016. The model considered six crash types—rear-end, angle, sideswipe, single-vehicle, multi-vehicle (three or more), and non-motorized crashes. The model estimation is conducted using an exhaustive set of independent variables. The model results clearly highlight the importance of accommodating zero crashes by crash type in the analysis. The model exercise is further augmented with a validation analysis.

Wheel Running Exacerbates Joint Damage after Meniscal Injury in Mice, but Does Not Alter Gait or Physical Activity Levels.

Exercise and physical activity are recommended to reduce pain and improve joint function in patients with knee osteoarthritis (OA). However, exercise has dose effects, with excessive exercise accelerating OA development and sedentary behaviors also promoting OA development. Prior work evaluating exercise in preclinical models has typically used prescribed exercise regimens; however, in-cage voluntary wheel running creates opportunities to evaluate how OA progression affects self-selected physical activity levels. This study aimed to evaluate how voluntary wheel running after a surgically induced meniscal injury affects gait characteristics and joint remodeling in C57Bl/6 mice. We hypothesize that injured mice will reduce physical activity levels as OA develops after meniscal injury and will engage in wheel running to a lesser extent than the uninjured animals. Seventy-two C57Bl/6 mice were divided into experimental groups based on sex, lifestyle (physically active vs sedentary), and surgery (meniscal injury or sham control). Voluntary wheel running data were continuously collected throughout the study, and gait data were collected at 3, 7, 11, and 15 wk after surgery. At end point, joints were processed for histology to assess cartilage damage. After meniscal injury, physically active mice showed more severe joint damage relative to sedentary mice. Nevertheless, injured mice engaged in voluntary wheel running at the same rates and distances as mice with sham surgery. In addition, physically active mice and sedentary mice both developed a limp as meniscal injury progressed, yet exercise did not further exacerbate gait changes in the physically active mice, despite worsened joint damage. Taken together, these data indicate a discordance between structural joint damage and joint function. Although wheel running after meniscal injury did worsen OA-related joint damage, physical activity did not necessarily inhibit or worsen OA-related joint dysfunction or pain in mice.

Revisiting policy combinations under IS–LM–EE framework introducing capacity utilization

The study introduces the capacity utilization factor into the existing works on the effect of technological progress towards environment friendly capital formation to analyse the impacts of fiscal and monetary policies in an IS–LM framework and concludes that the effects of fiscal and monetary policies on conservation capital and permit cost in the presence of technological progress cause increases in output, but these increases will centre around the full capacity utilization level. Further, the empirical exercise in a pooled regression model involving the income-influencing factors through fiscal and monetary policies shows that technological progress endowed with emission intensity and capacity utilization dummy for the world’s 28 countries, confirms the theoretical results in most circumstances. The study signifies the role of institutions and technological progress as the backbone to frame fiscal and monetary policies as an effective instrument for getting green growth.

Therapeutic and preventive effect of aerobic exercise in a GBM experimental model

Therapeutic and preventive effect of aerobic exercise in a GBM experimental model

Potential role of UCP-1 for mediating beneficial effects of exercise in an endometriosis rat model

Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue in areas outside the uterus. Previous studies in our laboratory demonstrated that endometriosis animals have increased mesenteric adipose tissue (MAT), inflammation, and implanted endometrial vesicles, which are all decreased by voluntary exercise. Interestingly, the levels of Uncoupling Protein 1 (UCP-1), a mitochondrial protein, are known to be increased by exercise promoting thermogenesis, and decreasing inflammation in rodents. However, the possible role of UCP-1 in endometriosis is still unclear. Our aim was to study the effects of exercise on UCP-1 in MAT near the endometrial implants in an endometriosis rat model. Hypothesis: UCP-1 increases due to exercise decreasing the MAT and thus beneficially impacts the endometrial vesicles. Methods: Endometriosis was induced by implanting uterine tissue on the intestinal mesentery in young adult female Sprague Dawley rats where the control group only received sutures. Exercise rats had access to a running wheel after induction: ENDO-EX or SHAM-EX, while non-exercised animals didn’t (ENDO and SHAM; n=10=11/group). After sixty days of intervention, animals were sacrificed and UCP-1 immunofluorescent staining was performed on collected MAT near the vesicles (ENDO, n=3; ENDO-EX, n=3; SHAM, n=4; SHAM-EX, n=4). Results: The vesicles from ENDO-EX animals had significantly decreased average weight (p<0.05) and smaller average total area (p<0.01) compared with the ENDO group. UCP-1 staining shows a trend to increase in exercise groups when compared to non-exercise groups. Interestingly, there is a moderate negative correlation between UCP-1 expression and vesicle size (r=-.69). Conclusions: Exercise is related to increasing the UCP-1 pathways in MAT that may be associated with decreasing the size of the endometrial vesicle implants. Supported by R15AT009915 and HRD-2008186. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Co-administration of exercise training and melatonin on the function of diabetic heart tissue: a systematic review and meta-analysis of rodent models

PurposeDiabetes mellitus (DM), a hyperglycemic condition, occurs due to the failure of insulin secretion and resistance. This study investigated the combined effects of exercise training and melatonin (Mel) on the function of heart tissue in diabetic rodent models.MethodsA systematic search was conducted in Embase, ProQuest, Cochrane library, Clinicaltrial.gov, WHO, Google Scholar, PubMed, Ovid, Scopus, Web of Science, Ongoing Trials Registers, and Conference Proceedings in July 2022 with no limit of date or language. All trials associated with the effect of Mel and exercise in diabetic rodent models were included. Of the 962 relevant publications, 58 studies met our inclusion criteria as follows; Mel and type 1 DM (16 studies), Mel and type 2 DM (6 studies), exercise and type 1 DM (24 studies), and exercise and type 2 DM (12 studies). Meta-analysis of the data was done using the Mantel Haenszel method.ResultsIn most of these studies, antioxidant status and oxidative stress, inflammatory response, apoptosis rate, lipid profiles, and glucose levels were monitored in diabetic heart tissue. According to our findings, both Mel and exercise can improve antioxidant capacity by activating antioxidant enzymes compared to the control diabetic groups (p < 0.05). The levels of pro-inflammatory cytokines, especially TNF-α were reduced in diabetic rodents after being treated with Mel and exercise. Apoptotic changes were diminished in diabetic rodents subjected to the Mel regime and exercise in which p53 levels and the activity of Caspases reached near normal levels (p < 0.05). Based on the data, both Mel and exercise can change the lipid profile in diabetic rodents, especially rats, and close it to near-to-control levels.ConclusionThese data showed that exercise and Mel can reduce the harmful effects of diabetic conditions on the heart through the regulation of lipid profile, antioxidant capacity, apoptosis, and inflammation.

Adropin is Involved in the Ameliorative Effect of Chronic Exercise in Non-alcoholic Fatty Liver Rat Model

Adropin is Involved in the Ameliorative Effect of Chronic Exercise in Non-alcoholic Fatty Liver Rat Model

Suppression of neuroinflammation and α-synuclein oligomerization by rotarod walking exercise in subacute MPTP model of Parkinson's disease

Parkinson's disease (PD) belongs to an α-synucleinopathy and manifests motor dysfunction attributed to nigrostriatal dopaminergic degeneration. In clinical practice, the beneficial role of physical therapy such as motor skill learning training has been recognized in PD-linked motor defects. Nevertheless, the disease-modifying effects of motor skill learning training on PD-related pathology remain unclear. Here, we investigated the disease-modifying effects of rotarod walking exercise (RWE), a modality of motor skill learning training, in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In motor function and dopaminergic degeneration, RWE improved MPTP-induced deficits. In addition, RWE enhanced the expression of neurotrophic factors BDNF/GDNF, PGC1-α, Nurr1, and p-AMPK, thereby recovering dopaminergic neuronal cell death. Moreover, RWE inhibited microglial activation and the expression of pro-inflammatory markers, such as p-IκBα, iNOS, IL-1β, TNF-α, and cathepsin D, while elevating anti-inflammatory IL-10 and TGF-β. RWE also decreased oxidative stress markers in the substantia nigra, such as 4-HNE and 8-OHdG-positive cells, while increasing Nrf2-controlled antioxidant enzymes. Regarding the effect of RWE on α-synuclein, it reduced the monomer/oligomer forms of α-synuclein and phosphorylation at serine 129. Further mechanistic studies revealed that RWE suppressed the expression of matrix metalloproteinase-3 and p-GSK3β (Y216), which play key roles in α-synuclein aggregation. These data collectively suggest that inhibition of neuroinflammation and α-synuclein oligomerization by RWE may contribute to the improvement of PD pathology.

Curcumin-Loaded Nanocomposite Hydrogel Augments Functional Muscle Recovery and Shows Synergistic Effects with Post-Injury Treadmill Exercise in a Muscle Injury Model in Rats: An In Vitro and In Vivo Study

Herein, the synergistic healing activity of treadmill exercise and curcumin-delivering hydrogel was evaluated in a rat model of skeletal muscle injury. In Vitro experiments were utilized to characterize the filler material and the healing potential of the treatment strategy was investigated in a rat model of anterior tibialis muscle injury. Study showed excellent biocompatibility of the hydrogel system. In Vivo study showed that the developed hydrogel and treadmill sport regimen significantly augmented muscle function recovery as evidenced by histopathological analysis. Gene expression studies showed that tissue expression levels of NFK-B and collagen type 1 genes were significantly downregulated in the animals treated with curcumin-loaded hydrogels with and without exercise.

Effect of aerobic exercise on AKT/GSK3β mediated hepatocyte apoptosis in nonalcoholic fatty liver disease

To investigate the effect of aerobic exercise on AKT/GSK3β pathway-mediated hepatocyte apoptosis in non-alcoholic fatty liver diseases(NAFLD). A total of 30 6-week-old male C57BL/6J mice, and mice were fed adaptively for one week. The control group was fed with ordinary diet, and the model group and model exercise group were fed with high-fat diet until 18 weeks. At the 10th week of the experiment, the model exercise group received aerobic exercise intervention for 8 consecutive weeks until the end of the experiment at the 18th week. Automatic biochemical analyzer to detect serum total cholesterol(TC), triglycerides(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST), low-density lipoprotein(LDL-C) and high-density lipoprotein(HDL-C) levels. Liver pathological morphology was observed by staining with oil red O and HE. The expression changes of AKT, P-AKT~( Ser473), GSK3β, P-GSK3β~(Ser9) and Caspase-3 proteins were detected by western blot, and the apoptosis of hepatocytes was detected by in situ terminal transferase labeling(TUNEL). (1) After intervention, compared with control group, body weight, liver index, serum TC, TG, ALT, AST and LDL-C levels in model group were significantly increased(P&lt;0.01 or P&lt;0.05), while HDL-C level was significantly decreased(P&lt;0.01). Compared with model group, body weight, liver index, serum TC, TG, ALT, AST and LDL-C levels in model exercise group were significantly decreased(P&lt;0.01 or P&lt;0.05), while HDL-C level was significantly increased(P&lt;0.01). (2) Compared with the control group, hepatocyte steatosis and the number of lipid droplets in model group were significantly increased. Compared with the model group, the degree of hepatic adipose degeneration was significantly improved and the number of hepatic lipid droplets was significantly decreased in the model exercise group. (3) Compared with control group, the protein expression levels of P-AKT~(Ser473) and P-GSK3β~(Ser9) in model group were significantly decreased(P&lt;0.01 or P&lt;0.05), the protein expression levels of Caspase-3 were significantly increased(P&lt;0.05), and the number of hepatocyte apoptosis was significantly increased(P&lt;0.05). Compared with model group, the expression of P-AKT~(Ser473) and P-GSK3β~(Ser9) protein in model exercise group was significantly increased(P&lt;0.01 or P&lt;0.05), the expression of Caspase-3 protein was significantly decreased(P&lt;0.05), and the number of hepatocyte apoptosis was significantly decreased(P&lt;0.01). Aerobic exercise can effectively improve NAFLD, by activating AKT/GSK3β pathway and increasing the expression of AKT/GSK3β pathway related molecules, thereby reducing caspase-3 expression and hepatocyte apoptosis.

The effectiveness of treadmill and swimming exercise in an animal model of osteoarthritis.

Introduction: Osteoarthritis (OA) is considered an inflammatory and degenerative joint disease, characterized by loss of hyaline joint cartilage and adjacent bone remodeling with the formation of osteophytes, accompanied by various degrees of functional limitation and reduction in the quality of life of individuals. The objective of this work was to investigate the effects of treatment with physical exercise on the treadmill and swimming in an animal model of osteoarthritis. Methods: Forty-eight male Wistar rats were divided (n=12 per group): Sham (S); Osteoarthritis (OA); Osteoarthritis + Treadmill (OA + T); Osteoarthritis + Swimming (OA + S). The mechanical model of OA was induced by median meniscectomy. Thirty days later, the animals started the physical exercise protocols. Both protocols were performed at moderate intensity. Forty-eight hours after the end of the exercise protocols, all animals were anesthetized and euthanized for histological, molecular, and biochemical parameters analysis. Results: Physical exercise performed on a treadmill was more effective in attenuating the action of pro-inflammatory cytokines (IFN-γ, TNF-α, IL1-β, and IL6) and positively regulating anti-inflammatories such as IL4, IL10, and TGF-β in relation to other groups. Discussion: In addition to maintaining a more balanced oxi-reductive environment within the joint, treadmill exercise provided a more satisfactory morphological outcome regarding the number of chondrocytes in the histological evaluation. As an outcome, better results were found in groups submitted to exercise, mostly treadmill exercise.

Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle.

Dynamic interaction between lipid droplets (LDs) and mitochondria controls the mobilization of long-chain fatty acids (LCFAs) from LDs for mitochondrial β-oxidation in skeletal muscle in response to energy stress. However, little is known about the composition and regulation of the tethering complex mediating LD-mitochondrion interaction. Here, we identify Rab8a as a mitochondrial receptor for LDs forming the tethering complex with the LD-associated PLIN5 in skeletal muscle. In rat L6 skeletal muscle cells, the energy sensor AMPK increases the GTP-bound active Rab8a that promotes LD-mitochondrion interaction through binding to PLIN5 upon starvation. The assembly of the Rab8a-PLIN5 tethering complex also recruits the adipose triglyceride lipase (ATGL), which couples LCFA mobilization from LDs with its transfer into mitochondria for β-oxidation. Rab8a deficiency impairs fatty acid utilization and decreases endurance during exercise in a mouse model. These findings may help to elucidate the regulatory mechanisms underlying the beneficial effects of exercise on lipid homeostasis control.

Early-stage Alzheimer's disease: are skeletal muscle and exercise the key?

Alzheimer's disease (AD) is the most common form of dementia affecting approximately 6.5 million people in the United States alone. The development of AD progresses over a span of years to possibly decades before resulting in cognitive impairment and clinically diagnosed AD. The time leading up to a clinical diagnosis is known as the preclinical phase, a time in which recent literature has noted a more severe loss of body mass and more specifically lean muscle mass and strength prior to diagnosis. Mitochondria dysfunction in neurons is also closely associated with AD, and mitochondrial dysfunction has been seen to occur in skeletal muscle with mild cognitive impairment prior to AD manifestation. Evidence from animal models of AD suggests a close link among skeletal muscle mass, mitochondria function, and cognition. Exercise is a powerful stimulus for improving mitochondria function and muscle health, and its benefits to cognition have been suggested as a possible therapeutic strategy for AD. However, evidence for beneficial effects of exercise in AD-afflicted populations and animal models has produced conflicting results. In this mini-review, we discuss these findings and highlight potential avenues for further investigation that may lead to the implementation of exercise as a therapeutic intervention to delay or prevent the development of AD.