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Strategies for improving cognition with aging: insights from a longitudinal study of antioxidant and behavioral enrichment in canines.

ABSTRACT: Studies in humans suggest that lifestyle factors can have a beneficial impact on the risk for developing cognitive decline and dementia with age. There is growing evidence that maintaining a physically and intellectually active lifestyle can positively impact cognitive ability in older individuals. Dietary factors, such as the intake of antioxidants, may also prevent age-related cognitive decline. However, studies in humans are challenging; many variables cannot be controlled, making it difficult for researchers to determine the exact types and quantities of enrichment and dietary factors necessary for positive effects on cognition. Studies in animal models of human aging allow researchers to precisely control such variables, and can be used to assess the mechanisms and molecular pathways underlying any positive effects. Here we review the results of an intervention study using a canine model of human aging. The study was unique in that it compared the effects of dietary antioxidant supplementation alone and in combination with behavioral enrichment. We found that both interventions lead to improvements in cognitive ability in aged dogs; however, combining the treatments preserved cognition to a greater extent than either treatment alone. Overall, the results suggest that antioxidant supplementation and behavioral enrichment target separate yet complementary molecular pathways to improve cognition, and support the idea that combinations of treatments to improve cognition and slow brain aging will produce greater benefits than single interventions.

SUBMITTER: Christie LA

PROVIDER: S-EPMC2734239 | biostudies-other | 2009 Sep

REPOSITORIES: biostudies-other

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Project description:Abstract Aging in older humans is associated with impaired mitochondrial fatty-acid oxidation (MFO), muscle weakness, cognitive decline and inflammation, but contributing mechanisms are not well understood and effective interventions are lacking. We proposed a unifying hypothesis that deficiency of the endogenous antioxidant protein Glutathione predisposes to all of these defects which are reversible on correcting Glutathione deficiency. To test our hypothesis, we conducted a 36-week open label clinical trial (NCT02348762) in 8 older humans (73.8 ± 1y) studied before and after 24-weeks of supplementation with N-acetylcysteine and Glycine (NAC-Gly, as Glutathione precursor amino-acids), and again 12-weeks after stopping supplements to determine washout changes. 8 young humans (25.8 ± 1y) served as controls, and were not supplemented. Study measures were intracellular Glutathione, fasted MFO (calorimetry), physical function (gait-speed, grip-strength, chair-rise and 6-minute walk tests), cognition (MoCA, Montreal Cognitive-Assessment; trail-making tests; verbal-fluency test; symbol-digital modalities test), plasma oxidative-stress (F2-isoprostanes), inflammation (Interleukein-6; Tumor Necrosis Factor alpha; C-reactive Protein) and body composition (DEXA-scan). Compared to young-controls, older humans had significantly (P<0.05 to P<0.01) impaired MFO, physical and cognitive decline, and higher inflammation and body fat. After 24-weeks of supplementation outcome measures improved significantly (P<0.05 to P<0.01), with complete normalization of fMFO (P<0.001), gait-speed (strength, P<0.001) and MoCA (cognition, P<0.01) to young controls. Accrued benefits declined on stopping supplementation. These novel discoveries provide a proof-of-concept for the exciting possibility that supplementing NAC-Gly in older humans could offer a novel nutritional approach to reverse age-related abnormalities in mitochondrial energetics, physical function, cognition, inflammation and body composition, and thereby ‘reverse aging’.

Project description:ObjectiveThe impact of cognitive function and decline on political ideology is unknown. We studied the relationship between cognition and both political orientation and political policy choices in a population of older persons.DesignLongitudinal investigation.SettingA retirement community and its surroundings in Southern California.Participants151 members of a longitudinal investigation of aging and dementia in the oldest-old (the 90+ Study), mean age 95 years.MeasurementsParticipants self-reported their political ideology (7-point scale from extremely liberal to extremely conservative) and policy preferences for federal spending on public schooling, aid to the poor, and protecting the environment, as well as on preferences on immigration rates, death penalty, and university admission. The same political survey was mailed to participants twice: at time one and 6-months later. Cognitive function based on neurological examination and cognitive testing was classified as normal (55%), cognitive impairment/not dementia (CIND) (33%), or dementia (12%). We calculated rank correlations between ideology and policy choices, stratified by cognitive status, and agreement between Surveys 1 and 2.ResultsPolitical ideology/orientation was highly consistent over a six-month period (84% agreement) among the 122 who returned the second survey, with no significant relationship to cognitive status. Among cognitively impaired (CIND and dementia), however, there was significant loss of consistency between an individual's political orientation and their policy choices. Level of political engagement was high for participants, with more than 90% voting in the 2016 presidential election.ConclusionIn this population of older persons, political identification on the liberal-conservative spectrum was resilient despite cognitive decline, but its meaning and function were changed. For the cognitively impaired it remained a self-defining label, but no longer operated as a higher order framework for orienting specific policy preferences. There appeared to be loss of coherence between the political orientation and political policy choices of cognitively impaired individuals. Given the high level of political engagement of these individuals, these results have substantial public policy implications.

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Strategies for improving cognition with aging: insights from a longitudinal study of antioxidant and behavioral enrichment in canines.

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