Curcumin and Yoga Therapy for Those at Risk for Alzheimer's Disease

Subjects with Mild cognitive impairment (MCI) or Subjective Cognitive Impairment (SCD) are
eligible for this study. MCI often represents the earliest stages of Alzheimer's disease
(AD), as individuals meeting criteria for MCI are subsequently diagnosed with AD at much
higher rates than their cognitively normal elderly peers. Subjects with MCI are at risk of
developing AD, within 6 years. Subjects with SCD may be at risk to develop MCI. The study is
stratified according to whether subjects have SCD or MCI. The goal of the current study is to
determine whether dietary supplementation with a novel formulation of curcumin (a component
of the curry spice turmeric), which is better absorbed and more efficiently transported into
the brain, can alter biological and clinical markers associated with AD risk, and to
determine whether the potential beneficial effects of curcumin supplementation are
synergistic with aerobic exercise. The investigators will recruit 80 elderly participants
meeting criteria for MCI. Over the second 6 months of the study, the curcumin and placebo
groups will be further divided into groups receiving training in either aerobic or
non-aerobic yoga to determine the synergism between curcumin supplementation and aerobic
exercise. The effectiveness of these interventions will be measured using plasma samples (for
expression of Alzheimer-related biomarkers), and neuropsychological, functional, and
behavioral assessments (i.e. clinical measures) collected at baseline, 6 months, and 12
months after initiation of treatments, with a subset of participants receiving brain imaging
at baseline and 6 months. Dosage is titered up two weeks prior to study start (1 capsule BID,
first five days, then 2 capsules BID for five days, then 6 capsules BID for five days, then 8
capsules BID- study dosage). Over the first 6 months of the study, participants will be
randomized into equal groups receiving dietary supplementation with either curcumin or
placebo. Patients are stratified according to whether they have only subjective memory
complaints without MCI versus those that have MCI. Over the second 6 months of the study,
participants will be further randomized into equal groups receiving dietary supplementation
with either curcumin or placebo.

Inclusion Criteria:

- age between 50 and 90 years;

- Mini-Mental Status Exam (MMSE) scores greater than 24;

- subjective cognitive complaints based on subjective cognitive impairment questionaire
(Gifford et al. 2015) including non-amnestic or amnestic cognitive deficits MCI
(performance 1.5 standard deviation (SD) below normative means on The Consortium to
Establish a Registry for Alzheimer's Disease (CERAD) word list learning test);

- essentially intact activities of daily living (FAQ scores < 6);

- Sedentary (exercise < 30 minutes a day, 3 times a week);

- ambulatory, able exercise safely without cardiovascular symptoms, and able to pass a
graded treadmill test modified for the elderly;

- able to arrange transportation to the study;

- Willing and intellectually able to understand and to sign an informed consent and to
adhere to protocol requirements;

- community dwelling; and

- fluent in written and spoken English

- must screen positive for a Modified abbreviated MCI or SCD screen on phone, before
coming in to clinic for extensive testing

Exclusion Criteria:

- diagnosis of dementia,

- concurrent substance abuse disorder,

- psychosis or mood disorder,

- neurological disease affecting motor or cognitive abilities (e.g. Parkinson's
disease),or other significant uncontrolled medical problems,

- cannot get up and down from floor

- initiation of any new medications/treatment for cognitive impairment (i.e.
cholinesterase inhibitor, memantine) < 6 months prior to study enrollment