U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk

Lifestyle interventions focused on combining healthy diet, physical activity, and social and
intellectual challenges may represent a promising therapeutic strategy to protect brain
health. The recent results of the population-based 2-year clinical trial, Finnish Geriatric
Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), indicated that a
multidomain intervention of physical activity, nutritional guidance, cognitive training,
social activities, and management of heart health risk factors protected cognitive function
in healthy older adults at increased risk of cognitive decline. As yet, there are no
pharmacological treatment options that can rival this effect. Thus, there is an urgent need
to expand this work to test the generalizability, adaptability and sustainability of its
findings in diverse and global populations. This pivotal U.S. Study to Protect Brain Health
through Lifestyle Intervention to Reduce Risk (U.S. POINTER) will test whether a similar
2-year intensive lifestyle intervention, adapted to American culture and delivered within the
community, can protect cognitive function in older adults in the U.S. who are at increased
risk for cognitive decline and dementia. If successful, the results of this study will have
large-scale implications for public policy regarding standard of clinical care and
prescriptive practices for a fast-growing and vulnerable population of older adults.

Inclusion Criteria:

- Sedentary

- Poor diet

- First-degree family history of a significant memory impairment (if unknown,
participant is ineligible)

- Cognitive function: no cognitive impairment

- Lives in a region where the POINTER interventions will be delivered

- Does not plan to travel outside of the home geographic area for more than 3 months
over the course of the study

- Free of physical disabilities that preclude participation in the study

- Willing to complete all study-related activities for 24 months

- Willing to be randomized to either lifestyle intervention group

Exclusion Criteria:

- Body mass index (BMI) >40

- Systolic blood pressure (BP), hemoglobin A1c (HbA1c), and lipids all conform to
current health guidelines for age (systolic BP <130mmHG; low-density lipoprotein (LDL)
cholesterol <130mg/dL; HbA1c <6.0%)

- Any significant neurologic disease, including any form of dementia, mild cognitive
impairment, Parkinson's disease, Huntington's disease, normal pressure hydrocephalus,
brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma,
multiple sclerosis, or history of significant head trauma with persistent neurologic
sequelae or known structural brain abnormalities

- Current or past use of medications for memory impairment or Alzheimer's disease (e.g.,
cholinesterase inhibitors, memantine)

- History of major depression within the last 12 months

- History of bipolar disorder or schizophrenia as per Diagnostic and Statistical manual
(DSM) V criteria

- History of alcohol or substance abuse or dependence within the past 2 years

- Use of psychoactive medications within the last 3 months including tricyclic
antidepressants, antipsychotics, mood-stabilizing psychotropic agents (e.g., lithium
salts), psychostimulants, opiate analgesics, antiparkinsonian medications,
anticonvulsant medications (except gabapentin and pregabalin for non-seizure
indications), systemic corticosteroids, or medications with significant central
anticholinergic activity; in the absence of major depression, stable dose use of
selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake
inhibitors are allowed

- Significant cardiovascular disease (including Class III or IV congestive heart
failure, clinically significant aortic stenosis, history of cardiac arrest, or
uncontrolled angina)

- Serious conduction disorder (e.g., 3rd degree heart block), uncontrolled arrhythmia,
or new Q waves or ST-segment depressions (>3mm) on ECG (treated atrial fibrillation
for more than 1 year or occasional premature ventricular contractions on ECG are not
exclusions)

- Myocardial infarction, major heart surgery (i.e., valve replacement, bypass surgery,
stent placement, angioplasty), deep vein thrombosis, or pulmonary embolus in the past
6 months

- Large vessel stroke in the past 2 years

- History of transient ischemia attack (TIA) or small vessel stroke in the last 6
months; TIA occurring more than 6 months ago with residual effects

- Past or current use of insulin to treat type 2 diabetes

- Lung disease requiring either regular use of corticosteroids or the use of
supplemental oxygen (inhaled steroids for asthma is permissible)

- Renal disease

- Clinically significant abnormalities in laboratory blood tests as per judgment of the
site Study Clinician

- History within the last 2 years of treatment for primary or recurrent malignant
disease, excluding non-melanoma skin cancers, resected cutaneous squamous cell
carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ
prostate cancer with normal prostate-specific antigen posttreatment

- History of hip fracture, joint replacement, or spinal surgery in the last 6 months

- Currently receiving physical therapy or cardiopulmonary rehabilitation

- History of a malabsorptive bariatric procedure (gastric bypass, biliopancreatic
diversion); other bariatric procedures involving restriction (i.e., sleeve, band) are
not exclusionary

- For women: currently pregnant, pregnant within the past 6 months, or planning to
become pregnant within the next 6 months.

- Resides in an assisted living facility or nursing home

- Receives hospice care

- Site PI/Study Clinician discretion regarding appropriateness of participation or
concern about intervention adherence