Feasibility of Improving Glycemia With Heat Therapy to Prevent AD

Aim 1. Examine the effects of heat therapy on blood glucose regulation in older adults at risk for AD. The Investigators will determine the ability of 10 weeks of heat therapy (3 days/week) to improve blood glucose regulation in older adults at risk for AD. Our primary outcome measures will be change in glycated hemoglobin (HbA1c), and change in insulin sensitivity index (ISI) assessed pre- vs post-intervention. The Investigators will also perform continuous glucose monitoring for 7 days prior to and following the intervention, as well as monitor dietary patterns during the intervention. The Investigators hypothesize that 10 weeks of heat therapy will lower HbA1c values and improve ISI outcomes.

Aim 2. Test the effect of heat therapy on brain glucose metabolism. To date, no studies have examined the impact of heat therapy on brain glucose metabolism. Here The Investigators will determine the effect of 10 weeks of heat therapy on brain glucose metabolism in older adults at risk for AD. Our primary outcome measure will be change in [18F] fluorodeoxyglucose (FDG) global standardized uptake value ratio (SUVR) pre- vs post- heat therapy. The Investigators hypothesize that individuals will improve (increase) global cerebral glucose metabolism following 10 weeks of heat therapy. The Investigators further hypothesize that the degree of change in blood glucose metabolism will track with change in brain glucose metabolism.

Aim 3. Explore the effect of heat therapy on fluid biomarkers (proteostasis, inflammation, neuropathology) and neuroimaging markers of brain health. The Investigators will explore the effect of heat therapy on plasma markers of proteostasis (HSP's), inflammation (CRP, TNF, IL-6, JNK and IKK) and AD-related neuropathology (Amyloid/Tau/Neurodegeneration; A/T/N measures) markers in plasma at baseline and following 10 weeks of heat treatment. The Investigators will also obtain MRI measures of resting state metabolism, brain blood flow, and oxygen uptake for preliminary characterization of intervention-related changes. The Investigators hypothesize that proteostasis, inflammation, and AD neuropathology will be beneficially affected by heat treatment. The Investigators further hypothesize that the team will observe benefits in MRI-related brain outcomes.

Inclusion criteria

• Age 65 and older
• Stable medication doses (>1 month)
• Post-menopausal
• Clinical Dementia Rating (CDR) of 0
• History of or current metabolic impairment (i.e. metabolic syndrome, pre-diabetes, Type 2 Diabetes, etc)

Exclusion criteria

• Excluded from or unable to complete an MRI scan. MRI compatible pacemakers will require cardiologist clearance prior to enrolling.
• ACSM Risk score stratification of "High" unless cleared by a physician prior to participation.
• Myocardial infarction or symptoms of coronary artery disease in the last 2 years.
• History of or current diagnosis of disorders with the potential to impair cognition (i.e. AD, Parkinson's disease, stroke (defined as clinical episode w/ neuroimaging evidence in appropriate area to explain symptoms)).
• Insulin-dependent (Type 1) Diabetes Mellitus.
• Clinically significant chronic disease such as cancer, HIV, or acquired immunodeficiency syndrome.
• Clinically significant depressive symptoms that may impair cognition, use of psychoactive and investigational medications, and significant visual or auditory impairment.
• Orthopedic complications that would preclude individuals from safely entering a hot tub.
• Untreated hypothyroidism or diseases associated with heat intolerance (i.e. Graves disease, etc).
• Contraindication for temperature pill ingestion (i.e. inflammatory bowel disease, diverticulitis or related).