Effect of Physical Exercise on Cognitive Function of Alzheimer's Disease Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trial

Liu, Wei; Zhang, Jia; Wang, Yanyan; Li, Junfeng; Chang, Jindong; Jia, Qingyin

doi:10.3389/fpsyt.2022.927128

Cited by 21 publications

(27 citation statements)

References 61 publications

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“…Exercise prior to the onset of AD pathology prevents the memory loss and loss of myelin in white matter in the APP/PS1 mouse AD model (Zhang et al, 2017). Physical exercise may improve cognitive function slightly in AD patients (Liu W. et al, 2022).…”

Section: Reversing White Matter Injury Improves Cognition In Animal A...mentioning

confidence: 99%

White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer’s disease (AD) neuropathology: A hypothesis and review

Sharp

DeCarli

Jin

et al. 2023

Front. Aging Neurosci.

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We postulate that myelin injury contributes to cholesterol release from myelin and cholesterol dysmetabolism which contributes to Abeta dysmetabolism, and combined with genetic and AD risk factors, leads to increased Abeta and amyloid plaques. Increased Abeta damages myelin to form a vicious injury cycle. Thus, white matter injury, cholesterol dysmetabolism and Abeta dysmetabolism interact to produce or worsen AD neuropathology. The amyloid cascade is the leading hypothesis for the cause of Alzheimer’s disease (AD). The failure of clinical trials based on this hypothesis has raised other possibilities. Even with a possible new success (Lecanemab), it is not clear whether this is a cause or a result of the disease. With the discovery in 1993 that the apolipoprotein E type 4 allele (APOE4) was the major risk factor for sporadic, late-onset AD (LOAD), there has been increasing interest in cholesterol in AD since APOE is a major cholesterol transporter. Recent studies show that cholesterol metabolism is intricately involved with Abeta (Aβ)/amyloid transport and metabolism, with cholesterol down-regulating the Aβ LRP1 transporter and upregulating the Aβ RAGE receptor, both of which would increase brain Aβ. Moreover, manipulating cholesterol transport and metabolism in rodent AD models can ameliorate pathology and cognitive deficits, or worsen them depending upon the manipulation. Though white matter (WM) injury has been noted in AD brain since Alzheimer’s initial observations, recent studies have shown abnormal white matter in every AD brain. Moreover, there is age-related WM injury in normal individuals that occurs earlier and is worse with the APOE4 genotype. Moreover, WM injury precedes formation of plaques and tangles in human Familial Alzheimer’s disease (FAD) and precedes plaque formation in rodent AD models. Restoring WM in rodent AD models improves cognition without affecting AD pathology. Thus, we postulate that the amyloid cascade, cholesterol dysmetabolism and white matter injury interact to produce and/or worsen AD pathology. We further postulate that the primary initiating event could be related to any of the three, with age a major factor for WM injury, diet and APOE4 and other genes a factor for cholesterol dysmetabolism, and FAD and other genes for Abeta dysmetabolism.

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Section: Reversing White Matter Injury Improves Cognition In Animal A...mentioning

confidence: 99%

White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer’s disease (AD) neuropathology: A hypothesis and review

Sharp

DeCarli

Jin

et al. 2023

Front. Aging Neurosci.

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“…Clinical trials of mild to moderate exercise in AD suggest a possible beneficial effect in some studies but several studies have not shown efficacy. 7,8 The two patients reported here suggest that vigorous, regular exercise, which has not been studied systematically in MCI or AD, may be needed to slow disease progression in biomarker-positive amnestic MCI or mild AD.…”

Section: Discussionmentioning

confidence: 95%

“…8 This discrepancy may be related to differing selection criteria for studies in meta-analyses, partly because of marked heterogeneity in physical exercise interventions and lack of blindness of raters in most studies. 7,8 Nearly all published studies have evaluated mild to moderate exercise for a few months to 2 years without regular exercise being required during the entire follow-up period. 7 Therefore, the potential diseasemodifying effect of vigorous, regular physical exercise over several years to decades in AD is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Vigorous, regular physical exercise may slow disease progression in Alzheimer's disease

Devanand

Masurkar

Wısnıewskı

2023

Alzheimer's & Dementia

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Introduction Mild to moderate exercise may decrease Alzheimer's disease (AD) risk, but the effects of vigorous, regular physical exercise remain unclear. Methods Two patients with initial diagnoses of amnestic mild cognitive impairment (MCI) demonstrated positive AD biomarkers throughout 16 and 8 years of follow‐up, with final diagnoses of mild AD and amnestic MCI, respectively. Results Patient 1 was diagnosed with amnestic MCI at age 64. Neuropsychological testing, magnetic resonance imaging (MRI), fluorodeoxyglucose–positron emission tomography (FDG‐PET), amyloid imaging PET, and cerebrospinal fluid (CSF) biomarkers during follow‐ups remained consistent with AD. By age 80, progression was minimal with Montreal Cognitive Assessment (MoCA) 26 of 30. Patient 2 was diagnosed with amnestic MCI at age 72. Neuropsychological testing, MRI, FDG‐PET, and amyloid imaging PET during follow‐ups remained consistent with AD. At age 80, MoCA was 27 of 30 with no clinical progression. Both patients regularly performed vigorous, regular exercise that increased after retirement/work reduction. Discussion Vigorous, regular exercise may slow disease progression in biomarker‐positive amnestic MCI and mild AD.

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“…However, in VR applications for AD patients, promoting a high level of immersion that corresponds to the experience of feeling "present" in the real world is critical to the patient's response to the intervention. In the available literature, we cannot yet determine whether fully immersive VR technologies are better than moderate or low immersion VR technologies (46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Effect of virtual reality exercise on interventions for patients with Alzheimer’s disease: A systematic review

Cui

et al. 2022

Front. Psychiatry

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Virtual reality (VR) interventions are increasingly being used in rehabilitating and treating patients with neurological disorders. This study aimed to explore the effects of VR exercise interventions for patients with Alzheimer’s disease (AD). A systematic review of the published literature on randomized controlled trials of VR technology applied to patients with AD was conducted using the preferred reporting entry for systematic reviews and Meta-analysis guidelines. Descriptive analyses were performed to assess the quality of the studies in terms of the characteristics of the included studies, samples, diagnoses, types of VR technologies, subjective and objective levels of immersion, and quality of studies. Eight studies were included, including a pooled sample of 362 patients with AD. A systematic review showed that most studies focused on patients with AD’s cognitive and physical functions. The main finding was that VR interventions could help improve cognitive and physical balance in patients with AD. However, future studies should emphasize design and use well-accepted assessment tools to validate the effects of VR interventions further.

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Effect of Physical Exercise on Cognitive Function of Alzheimer's Disease Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trial

Cited by 21 publications

References 61 publications

White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer’s disease (AD) neuropathology: A hypothesis and review

White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer’s disease (AD) neuropathology: A hypothesis and review

Vigorous, regular physical exercise may slow disease progression in Alzheimer's disease

Effect of virtual reality exercise on interventions for patients with Alzheimer’s disease: A systematic review

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