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Principal Investigator: Breno Satler Diniz
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $1,803,334
Funding agency: National Institute on Aging
Abstract:
Exercise and mindfulness are believed to be effective stress reduction interventions, but research to date has
not been able to assess their benefits while individuals are coping with a major stressor in real time. The
COVID-19 pandemic is an unwanted natural experiment in the deleterious effects of stress – especially social
isolation (social disconnectedness and loneliness), a stressor particularly strongly associated with the
pandemic - on older Americans’ cognitive and emotional health and risk for Alzheimer’s Disease (AD). This
project will elucidate whether exercise and mindfulness can mitigate the effects of pandemic stress on
cognitive function and emotional health in later life, including neurobiological measures of risk for AD.
We will leverage a unique resource: the NIH-funded trial, “Mindfulness-Based Stress Reduction and Exercise
for Age-Related Cognitive Decline” (MEDEX). By leveraging MEDEX and following these participants, who
continue to attend monthly booster sessions of their randomized condition remotely during the pandemic, we
will have repeated sets of clinical, cognitive, molecular, and neuroimaging measures covering 7.5 years during
the pre-, during-, and post-pandemic period. We can examine intervention effects, as well as individual factors
such as resilience, on long-term outcomes. Among other innovative aspects of the project, we will analyze
effects on two novel peripheral biomarkers: Senescence-Associated Secretory Phenotype (SASP), which
measures mechanisms of biological aging, and plasma amyloid Aβ42 and Aβ40, which measure AD risk.
In the proposed project, (1) during the pandemic, we will use novel methods such as Ecological Momentary
Assessment (EMA) to characterize social isolation both objectively (e.g., number of social contacts) and
subjectively (e.g., loneliness), and its biological mechanisms on aging (such as elevations in SASP and plasma
amyloid); (2) post-pandemic, we will assess downstream effects on cognitive function, emotional well-being,
and brain health, including AD risk, using neuropsychological assessments, EMA, and neuroimaging.
Outcomes include (Aim 1) changes in cognitive performance and emotional well-being, and decline in
emotional well-being measured by positive and negative affect and sleep quality; increases in biological aging
and decreasing AΒ42/40 ratio in the post-pandemic phase, indicating higher risk of AD; atrophy in hippocampal
and prefrontal volume (structural MRI) and reduced global functional connectivity (resting-state fMRI).
Modifiers of these effects (Aim 2) include exercise and mindfulness; psychological resilience; COVID-19
exposure; medical morbidities; and APOE genotype. Mechanisms of cognitive, emotional, and brain health
changes (Aim 3) include amyloid (Aβ40 and Aβ42), SASP, DNA methylation, and cortisol during the pandemic.
This project will advance our knowledge of the impact of social isolation and other stressors on older adults,
including mechanisms by which these stressors produce deleterious cognitive, emotional, and brain health
changes over time, and whether exercise and mindfulness have durable protective effects.
Terms: <21+ years old><A β-42><A β42><A-beta 42><A-beta42><AD dementia><Abeta-42><Abeta42><Active Follow-up><Adult><Adult Human><Aeroseb-HC><Age-associated cognitive decline><Age-associated memory impairment><Age-related cognitive decline><Aging><Alzheimer Type Dementia><Alzheimer beta-Protein><Alzheimer disease dementia><Alzheimer risk factor><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Amyloid beta-Protein><Alzheimer's Disease><Alzheimer's amyloid><Alzheimer's disease risk><Alzheimers Dementia><American><Ammon Horn><Amyloid><Amyloid Alzheimer's Dementia Amyloid Protein><Amyloid Beta-Peptide><Amyloid Protein A4><Amyloid Substance><Amyloid beta-42><Amyloid beta-Protein><Amyloid beta42><Amyloid β><Amyloid β-42><Amyloid β-Peptide><Amyloid β-Protein><Amyloid β42><Amyloidβ-42><Amyloidβ42><Anxiety><Atrophic><Atrophy><Aβ><Aβ-42><Aβ42><Behavioral><Benign senescent forgetfulness><Biological><Biological Aging><Biological Markers><Blood Plasma><Brain><Brain Nervous System><Buffers><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 exposure><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cetacort><Clinical><Clinical Trials><Cognition><Cognitive><Cornu Ammonis><Cort-Dome><Cortef><Cortenema><Cortisol><Cortispray><Cortril><DNA Methylation><Dermacort><Ecological momentary assessment><Eldecort><Emotional><Emotional well being><Encephalon><Enrollment><Episodic memory><Exercise><Exercise Test><Feels well><Functional MRI><Functional Magnetic Resonance Imaging><Funding><Genotype><Goals><Health><Health Instruction><Health Tutoring><Health education><Hippocampus><Hydrocortisone><Hydrocortone><Hytone><Individual><Intervention><Intervention Strategies><Knowledge><Life Style><Lifestyle><Loneliness><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Measures><Medical><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Memory><Mental Depression><Methods><Modeling><Molecular><Morbidity><Morbidity - disease rate><NIH><NMR Imaging><NMR Tomography><National Institutes of Health><Natural experiment><Neurobiology><Neuropsychologies><Neuropsychology><Normal mental condition><Normal mental state><Normal psyche><Nuclear Magnetic Resonance Imaging><Nutracort><Outcome><Participant><Peripheral><Personal Satisfaction><Phase><Physiologic><Physiological><Plasma><Plasma Serum><Primary Senile Degenerative Dementia><Proctocort><Psychological Well Being><Public Health><Randomized><Research><Research Resources><Resources><Rest><Reticuloendothelial System, Serum, Plasma><Risk-associated variant><SARS-CoV-2 epidemic><SARS-CoV-2 exposure><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV2 exposure><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Salivary><Sense of well-being><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 pandemic><Social isolation><Stress><Structure><Testing><Time><United States National Institutes of Health><Well in self><Zeugmatography><a beta peptide><abeta><active followup><adulthood><age associated effects><age associated memory decline><age effect><age related cognitive deficit><age related cognitive impairment><age related effects><age related memory dysfunction><age-induced cognitive decline><age-related decline in cognition><age-related decline in cognitive function><aged><aging effect><alzheimer risk><amyloid beta><amyloid-b protein><beta amyloid fibril><bio-markers><biologic><biologic marker><biological process of age><biomarker><brain health><cognitive control><cognitive function><cognitive performance><coping><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 exposure><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><depression><emotional wellbeing><emotional wellness><enroll><executive control><executive function><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><fMRI><follow up><follow-up><followed up><followup><high risk><hippocampal><impact of age><influence of age><innovate><innovation><innovative><intervention effect><interventional strategy><late life><life style intervention><lifestyle intervention><lonely><mental well-being><mental wellbeing><mental wellness><mindfulness><mindfulness-based stress reduction><mobile assessment><mobile based assessment><negative affect><negative affectivity><neural imaging><neuro-imaging><neurobiological><neuroimaging><neurological imaging><neuropsychologic><novel><older adult><older adulthood><pandemic><pandemic associated stress><pandemic disease><pandemic effect><pandemic impact><pandemic induced stress><pandemic outcome><pandemic related stress><pandemic repercussions><pandemic stress><post-pandemic><prevent><preventing><primary degenerative dementia><protective effect><psychologic><psychological><psychological wellbeing><psychological wellness><quality of sleep><randomisation><randomization><randomly assigned><resilience><resilient><risk allele><risk gene><risk genotype><risk loci><risk locus><risk variant><satisfaction><self wellness><senescence associated secretome><senescence associated secretory phenotype><senile dementia of the Alzheimer type><sense of wellbeing><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sleep quality><smart phone based assessment><smartphone based assessment><social><social contact><social engagement><social involvement><social participation><soluble amyloid precursor protein><stress due to pandemic><stress during the pandemic><stress reduction><stressor><virtual><well-being><wellbeing>