Brain pathology is related to total daily physical activity in older adults

Buchman, Aron S.; Dawe, Robert J.; Yu, Lei; Lim, Andrew; Wilson, Robert S.; Schneider, Julie A.; Bennett, David A.

doi:10.1212/wnl.0000000000005552

Cited by 28 publications

(47 citation statements)

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“…4,5 We have also found that AD and other brain pathologies are associated with motor phenotypes including physical activity. [6][7][8] Furthermore, we found that physical activity modified the relation of white matter changes to motor function in older persons. 9 This raises the possibility that a more active lifestyle may modify the association of brain pathologies with cognition.…”

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confidence: 69%

Physical activity, common brain pathologies, and cognition in community-dwelling older adults

Buchman

Wilson

et al. 2019

Neurology

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ObjectiveTo examine the associations of physical activity, Alzheimer disease (AD), and other brain pathologies and cognition in older adults.MethodsWe studied 454 brain autopsies from decedents in a clinical-pathologic cohort study. Nineteen cognitive tests were summarized in a global cognitive score. Total daily physical activity summarized continuous multiday recordings of activity during everyday living in the community setting. A global motor ability score summarized 10 supervised motor performance tests. A series of regression analyses were used to examine associations of physical activity, AD, and other brain pathologies with global cognition proximate to death controlling for age, sex, education, and motor abilities.ResultsHigher levels of total daily activity (estimate 0.148, 95% confidence interval 0.053–0.244, SE 0.049, p = 0.003) and better motor abilities (estimate 0.283, 95% confidence interval, 0.175–0.390, SE 0.055, p < 0.001) were independently associated with better cognition. These independent associations remained significant when terms for AD and other pathologies were added as well as in sensitivity analyses excluding cases with poor cognition or dementia. Adding interaction terms, the associations of total daily activity and motor abilities with cognition did not vary in individuals with and without dementia. The associations of AD and other pathologies with cognition did not vary with the levels of total daily activity or motor abilities.ConclusionsPhysical activity in older adults may provide cognitive reserve to maintain function independent of the accumulation of diverse brain pathologies. Further studies are needed to identify the molecular mechanisms underlying this potential reserve and to ensure the causal effects of physical activity.

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Physical activity, common brain pathologies, and cognition in community-dwelling older adults

Buchman

Wilson

et al. 2019

Neurology

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“…6). The 3 locomotor activity parameters represent well-established aging-related locomotor impairments that are welldocumented in humans [11][12][13][14][15]49,68,69 . The BNF rat strain used emulates aging-related locomotor decline seen across rodents, non-human primates, and humans with decreased movement initiation frequency or ability 72 , exhibiting motor decline beginning in the middle to latter half of the lifespan 40,48,66 and further decreasing out to 30 months of age 26,31 .…”

Section: Discussionmentioning

confidence: 99%

“…The BNF rat strain used emulates aging-related locomotor decline seen across rodents, non-human primates, and humans with decreased movement initiation frequency or ability 72 , exhibiting motor decline beginning in the middle to latter half of the lifespan 40,48,66 and further decreasing out to 30 months of age 26,31 . While recognizing that aging produces a number of changes in dopamine neurotransmission and in other CNS components, nigral neuron loss is independently associated with physical activity proximate to death 49 . Our results support the possibility that aging-related loss of TH protein or DA in the SN, possibly due to neuron loss 49 , is a contributing neurobiological mechanism of aging-related decreases in movement frequency.…”

Section: Discussionmentioning

confidence: 99%

“…While recognizing that aging produces a number of changes in dopamine neurotransmission and in other CNS components, nigral neuron loss is independently associated with physical activity proximate to death 49 . Our results support the possibility that aging-related loss of TH protein or DA in the SN, possibly due to neuron loss 49 , is a contributing neurobiological mechanism of aging-related decreases in movement frequency.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of nigral neurons is independently associated with reduced physical activity proximate to death in older adults 49 . However, the possibility that loss of DA or TH in the SN similar to that in aging could contribute to motor decline has not been systematically interrogated.…”

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Tyrosine Hydroxylase Inhibition in Substantia Nigra Decreases Movement Frequency

et al. 2018

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Reduced movement frequency or physical activity (bradykinesia) occurs with high prevalence in the elderly. However, loss of striatal tyrosine hydroxylase (TH) in aging humans, non-human primates, or rodents does not reach the ~ 80% loss threshold associated with bradykinesia onset in Parkinson's disease. Moderate striatal dopamine (DA) loss, either following TH inhibition or decreased TH expression, may not affect movement frequency. In contrast, moderate DA or TH loss in the substantia nigra (SN), as occurs in aging, is of similar magnitude (~ 40%) to nigral TH loss at bradykinesia onset in Parkinson's disease. In aged rats, increased TH expression and DA in SN alone increases movement frequency, suggesting aging-related TH and DA loss in the SN contributes to aging-related bradykinesia or decreased physical activity. To test this hypothesis, the SN was targeted with bilateral guide cannula in young (6 months old) rats, in a within-subjects design, to evaluate the impact of nigral TH inhibition on movement frequency and speed. The TH inhibitor, α-methyl-p-tyrosine (AMPT) reduced nigral DA (~ 40%) 45-150 min following infusion, without affecting DA in striatum, nucleus accumbens, or adjacent ventral tegmental area. Locomotor activity in the open-field was recorded up to 3 h following nigral saline or AMPT infusion in each test subject. During the period of nigra-specific DA reduction, movement frequency, but not movement speed, was significantly decreased. These results indicate that DA or TH loss in the SN, as observed in aging, contributes as a central mechanism of reduced movement frequency.

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Association of White Matter Hyperintensities With Pathology and Progression of Parkinsonism in Aging

Oveisgharan

Poole

et al. 2021

JAMA Neurol

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IMPORTANCEProgressive parkinsonism is common in older adults without a diagnosis of Parkinson disease and is associated with adverse health outcomes, but its pathologic basis is controversial.OBJECTIVE To examine if the burden of cerebral white matter hyperintensity (WMH), a common manifestation of cerebrovascular disease pathologies, is associated with the rate of progressive parkinsonism. DESIGN, SETTING, AND PARTICIPANTSThis community-based cohort study included participants recruited in 3 ongoing cohorts that began enrollment in 1994, 1997, and 2004. Prior to death, participants were observed for a mean of 7.5 years, with annual clinical assessments. From 4427 participants enrolled in the 3 cohorts, 2134 died. Postmortem autopsy was performed in 1725 decedents, and 598 also had ex vivo brain magnetic resonance imaging. Participants were excluded if they were missing any of the 9 postmortem pathology indices (n = 22) or repeated parkinsonism assessment (n = 41) or had received a clinical diagnosis of Parkinson disease at any point before or during the study (n = 19). Data were analyzed from April 2020 to August 2021.EXPOSURES WMH burden was assessed using a modified Fazekas rating scale.MAIN OUTCOMES AND MEASURES Parkinsonism was assessed annually using 26 items of a modified motor portion of the Unified Parkinson's Disease Rating Scale. A summary score was developed from the item scores, with higher scores indicating more severe parkinsonism. RESULTSOf 516 included decedents, 364 (70.5%) were female, and the mean (SD) age at death was 90.2 (6.4) years. Higher WMH was associated with faster progressive parkinsonism (estimate, 0.024; SE, 0.008; P = .002). The attenuation of this association was greater when controlling for indices of cerebrovascular disease pathologies than when controlling for neurodegenerative pathologies (cerebrovascular disease: estimate, 0.019; SE, 0.008; P = .02; neurodegenerative: estimate, 0.022; SE, 0.008; P = .003), but both remained significant. CONCLUSIONS AND RELEVANCEIn this cohort study, higher levels of both WMH and indices of cerebrovascular disease pathologies in aging brains were associated with more rapid progressive parkinsonism. Further studies are needed to determine if in vivo brain imaging of older adults for evidence of WMH and aggressive medical treatment of vascular risk factors and diseases can reduce the occurrence or severity of late-life parkinsonism.

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Brain pathology is related to total daily physical activity in older adults

Abstract: Macroinfarcts, nigral neuronal loss, and white matter pathologies are related to total daily physical activity in older adults, but further studies are needed to explain its pathologic basis more fully.

Cited by 28 publications

References 41 publications

Physical activity, common brain pathologies, and cognition in community-dwelling older adults

Physical activity, common brain pathologies, and cognition in community-dwelling older adults

Tyrosine Hydroxylase Inhibition in Substantia Nigra Decreases Movement Frequency

Association of White Matter Hyperintensities With Pathology and Progression of Parkinsonism in Aging

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