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Objective: Physical activity (PA) has been linked to reduced Alzheimer's disease (AD) risk. However, less is known about its effects in the AD preclinical stage. We aimed to investigate whether greater PA was associated with lower plasma biomarkers of AD pathology, neural injury, reactive astrocytes, and better cognition in individuals with autosomal‐dominant AD due to the presenilin‐1 E280A mutation who are virtually guaranteed to develop dementia. Methods: Twenty‐eight cognitively unimpaired mutation carriers (ages x̄ = 29.28) wore a FitBit Charge‐4 for 14 days. We calculated their average steps to measure locomotion, and Training Impulse (TRIMP) to quantify the intensity and duration of PAs using heart rate. Plasma amyloid beta 42/40 ratio, phosphorylated tau 181, neurofilament light chain, and glial fibrillary acidic protein (GFAP) were measured. Cognition was assessed with the Consortium to Establish a Registry for Alzheimer's Disease word list learning and delayed recall, Trail Making Test Part A, and Wechsler Adult Intelligence Scale‐version IV Digit Span Backward. We conducted multiple linear regressions controlling for age, sex, body mass index, and education. Results: There were no associations among steps or TRIMP with plasma biomarkers or cognition. Greater TRIMP was related to higher GFAP levels. Conclusions: PA was not associated with cognition or plasma biomarkers. However, greater intensity and duration of PAs were related to higher GFAP. Participants engaged very little in moderate to vigorous PA. Therefore, light PA may not exert a significant protective effect in preclinical AD. Future work with larger samples and longitudinal data is needed to elucidate further the potential impact of PA on AD progression in the preclinical stages. Highlights: Locomotion (average steps) was not associated with plasma biomarkers or cognition.Greater training load (training impulse) was related to higher glial fibrillary acidic protein levels in mutation carriers.Light physical activity may not suffice to exert a protective effect on Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of cardiometabolic disease following spinal cord injury is known to be high. However, it is unknown whether engaging in high‐intensity exercise, which is advocated by recent guidelines, is beneficial or feasible for these individuals. Objective: To assess the effects of high‐intensity, whole‐body exercise on the prevalence of cardiometabolic disease in individuals with spinal cord injury. Design: Combination of a randomized controlled trial and an open label intervention study of functional electrical stimulation legs plus arms rowing. Setting: Outpatient academic rehabilitation hospital. Participants: Forty individuals with spinal cord injury, with American Spinal Injury Association (ASIA) impairments scales A‐D and neurological levels of injury C1‐T12. Intervention: Six months of high‐intensity, hybrid‐functional electrical stimulation rowing. Main Outcome Measures: Change in VO2max, serum lipids, and insulin resistance, prevalence of cardiometabolic disease. Results: Individuals averaged 42.1 ± 22.0 minutes of hybrid‐functional electrical stimulation rowing a week over an average of 1.69 sessions per week over the 6 months of intervention. This amounted to an average of 170.9 ± 100 km rowed, at a mean heart rate of 82.7% of individualized maximum. Only one of 40 individuals met current exercise guidelines for the full 6 months. VO2max increased significantly (P <.001), yet prevalence of cardiometabolic disease did not change significantly (decrease from 22.5% to 20%, P =.70). Hemoglobin A1c did decrease significantly over this time (P =.01), although serum lipids and fasting glucose/insulin levels were unchanged. In exploratory subanalyses assessing individuals injured ≤12 months, those with more chronic injuries decreased their triglyceride‐to‐high‐density lipoprotein (HDL) ratio (P =.04), a marker of cardiac mortality. Stratifying by neurological level of injury, individuals with paraplegia had worsened low‐density lipoprotein (LDL) level (P =.02) and total cholesterol‐to‐HDL ratio (P =.04) over the 6‐month intervention. Conclusions: Sustained high‐intensity exercise with hybrid functional electrical stimulation rowing does not decrease the prevalence of cardiometabolic disease after spinal cord injury. [ABSTRACT FROM AUTHOR]

Background: Functional electrical stimulation (FES) is widely used to induce functional movements for paralyzed muscles. However, rapid muscle fatigue during FES-induced muscle contractions limits FES clinical efficacy.Objective: To investigate muscle fatigue response across stimulation patterns and frequencies during FES in able-bodied individuals and in those with spinal cord injury (SCI).Design: Four stimulation protocols combining 20 and 40 Hz average frequency with either constant frequency trains (CFTs) or with doublet frequency trains (DFTs) were applied to the quadriceps of seven adults with SCI and eight able-bodied participants.Setting: A FES-row training laboratory.Participants: Seven individuals with SCI (one female; age range, 25 ± 6 years) and eight age-matched able-bodied participants (one female).Intervention: None.Main Outcome Measures: Fatigue was defined as the number of contractions until force decreased by 20% from the target level of 25% maximal contraction force. The number of contractions and the stimulation current used during the four stimulation protocols were compared.Results: There was a significant effect of frequency, as well as interaction between group and stimulation pattern (P < .05). In both groups, 20-Hz trains increased the number of contractions to fatigue compared to 40-Hz trains. However, the responses to the pattern of stimulation differed. In the able-bodied participants, CFT increased the number of contractions to fatigue compared to DFT, whereas in those with SCI, DFT increased the number of contractions to fatigue. In fact, DFT resulted in similar number of contractions to fatigue in both populations.Conclusions: These results indicate that DFT at 20 Hz may be a better stimulation protocol to delay fatigue onset in the SCI population than the other three protocols. In addition, this work implies that results from able-bodied persons may not be directly applicable to those with SCI. [ABSTRACT FROM AUTHOR]

Objective: Physical activity (PA) has been linked to reduced Alzheimer's disease (AD) risk. However, less is known about its effects in the AD preclinical stage. We aimed to investigate whether greater PA was associated with lower plasma biomarkers of AD pathology, neural injury, reactive astrocytes, and better cognition in individuals with autosomal-dominant AD due to the presenilin-1 E280A mutation who are virtually guaranteed to develop dementia., Methods: Twenty-eight cognitively unimpaired mutation carriers (ages x̄ = 29.28) wore a FitBit Charge-4 for 14 days. We calculated their average steps to measure locomotion, and Training Impulse (TRIMP) to quantify the intensity and duration of PAs using heart rate. Plasma amyloid beta 42/40 ratio, phosphorylated tau 181, neurofilament light chain, and glial fibrillary acidic protein (GFAP) were measured. Cognition was assessed with the Consortium to Establish a Registry for Alzheimer's Disease word list learning and delayed recall, Trail Making Test Part A, and Wechsler Adult Intelligence Scale-version IV Digit Span Backward. We conducted multiple linear regressions controlling for age, sex, body mass index, and education., Results: There were no associations among steps or TRIMP with plasma biomarkers or cognition. Greater TRIMP was related to higher GFAP levels., Conclusions: PA was not associated with cognition or plasma biomarkers. However, greater intensity and duration of PAs were related to higher GFAP. Participants engaged very little in moderate to vigorous PA. Therefore, light PA may not exert a significant protective effect in preclinical AD. Future work with larger samples and longitudinal data is needed to elucidate further the potential impact of PA on AD progression in the preclinical stages., Highlights: Locomotion (average steps) was not associated with plasma biomarkers or cognition.Greater training load (training impulse) was related to higher glial fibrillary acidic protein levels in mutation carriers.Light physical activity may not suffice to exert a protective effect on Alzheimer's disease., Competing Interests: Quiroz and Lopera serve as consultants for Biogen. Guzmán‐Vélez serves as a consultant for VarMed Management outside the submitted work. Arnold has consulted and/or served on advisory boards for Allyx Therapeutics, BioVie, Bob's Last Marathon, Daewoong Pharmaceuticals, Foster & Eldridge, LLP, Quince Therapeutics, Sage Therapeutics, and Vandria. He has received sponsored research grant support via his institution from the following commercial entities: AbbVie, Amylyx, Athira Pharma, Chromadex, Cyclerion Therapeutics, EIP Pharma, Ionis Pharmaceuticals, Janssen Pharmaceuticals, Inc., Novartis AG, Seer Biosciences, Inc., and vTv Therapeutics, Inc. He has received sponsored research grant support via his institution from the following non‐commercial entities: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Challenger Foundation, Cure Alzheimer's Fund, John Sperling Foundation, the National Institutes of Health, and the Prion Alliance. All other co‐authors have no conflicting interests to disclose. Author disclosures are available in the supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: The prevalence of cardiometabolic disease following spinal cord injury is known to be high. However, it is unknown whether engaging in high-intensity exercise, which is advocated by recent guidelines, is beneficial or feasible for these individuals., Objective: To assess the effects of high-intensity, whole-body exercise on the prevalence of cardiometabolic disease in individuals with spinal cord injury., Design: Combination of a randomized controlled trial and an open label intervention study of functional electrical stimulation legs plus arms rowing., Setting: Outpatient academic rehabilitation hospital., Participants: Forty individuals with spinal cord injury, with American Spinal Injury Association (ASIA) impairments scales A-D and neurological levels of injury C1-T12., Intervention: Six months of high-intensity, hybrid-functional electrical stimulation rowing., Main Outcome Measures: Change in VO 2max , serum lipids, and insulin resistance, prevalence of cardiometabolic disease., Results: Individuals averaged 42.1 ± 22.0 minutes of hybrid-functional electrical stimulation rowing a week over an average of 1.69 sessions per week over the 6 months of intervention. This amounted to an average of 170.9 ± 100 km rowed, at a mean heart rate of 82.7% of individualized maximum. Only one of 40 individuals met current exercise guidelines for the full 6 months. VO 2max increased significantly (P < .001), yet prevalence of cardiometabolic disease did not change significantly (decrease from 22.5% to 20%, P = .70). Hemoglobin A1c did decrease significantly over this time (P = .01), although serum lipids and fasting glucose/insulin levels were unchanged. In exploratory subanalyses assessing individuals injured ≤12 months, those with more chronic injuries decreased their triglyceride-to-high-density lipoprotein (HDL) ratio (P = .04), a marker of cardiac mortality. Stratifying by neurological level of injury, individuals with paraplegia had worsened low-density lipoprotein (LDL) level (P = .02) and total cholesterol-to-HDL ratio (P = .04) over the 6-month intervention., Conclusions: Sustained high-intensity exercise with hybrid functional electrical stimulation rowing does not decrease the prevalence of cardiometabolic disease after spinal cord injury., (© 2020 American Academy of Physical Medicine and Rehabilitation.)

Background: Functional electrical stimulation (FES) is widely used to induce functional movements for paralyzed muscles. However, rapid muscle fatigue during FES-induced muscle contractions limits FES clinical efficacy., Objective: To investigate muscle fatigue response across stimulation patterns and frequencies during FES in able-bodied individuals and in those with spinal cord injury (SCI)., Design: Four stimulation protocols combining 20 and 40 Hz average frequency with either constant frequency trains (CFTs) or with doublet frequency trains (DFTs) were applied to the quadriceps of seven adults with SCI and eight able-bodied participants., Setting: A FES-row training laboratory., Participants: Seven individuals with SCI (one female; age range, 25 ± 6 years) and eight age-matched able-bodied participants (one female)., Intervention: None., Main Outcome Measures: Fatigue was defined as the number of contractions until force decreased by 20% from the target level of 25% maximal contraction force. The number of contractions and the stimulation current used during the four stimulation protocols were compared., Results: There was a significant effect of frequency, as well as interaction between group and stimulation pattern (P < .05). In both groups, 20-Hz trains increased the number of contractions to fatigue compared to 40-Hz trains. However, the responses to the pattern of stimulation differed. In the able-bodied participants, CFT increased the number of contractions to fatigue compared to DFT, whereas in those with SCI, DFT increased the number of contractions to fatigue. In fact, DFT resulted in similar number of contractions to fatigue in both populations., Conclusions: These results indicate that DFT at 20 Hz may be a better stimulation protocol to delay fatigue onset in the SCI population than the other three protocols. In addition, this work implies that results from able-bodied persons may not be directly applicable to those with SCI., (© 2019 American Academy of Physical Medicine and Rehabilitation.)