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

– Sedentary (not a regular exerciser, determined using the POINTER Physical Activity
Questionnaire)

– Poor diet (as per the MIND Diet Screener)

– No cognitive impairment as per TICSm score >32 (includes adjustments for demographics
such as age, education and race), the Clinical Dementia Rating Scale (CDR <0.5), and the CDR-Sum of Boxes (CDR-SB <1) - Risk Score for cognitive decline >2, using the following scoring algorithm:

1 pt: Suboptimum cardiovascular health (treated or untreated): systolic BP >125 mmHg
~OR~ LDL cholesterol >115 mg/dL~OR~ glycated hemoglobin (HbA1c) >6.0%

1 pt: First degree family history (mother, father, sister, brother) of memory
impairment

1 pt: Race/ethnicity: African American/Black, Native American, or Hispanic/Latinx

1 pt: Older age: 70-79 years

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

– Does not plan to travel outside of the home geographic area for an extended period of
time during study participation

– Free of physical disabilities that preclude participation

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

– Willing to be randomized to either lifestyle intervention group

Exclusion Criteria

– Age <60 or ≥80 years - BMI >40

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

– History of major depression within the last 6 months

– History of bipolar disorder or schizophrenia as per DSM V criteria

– History of alcohol or substance abuse or dependence within the past 2 years, as per
DSM V criteria

– Current or past use of medications for memory impairment or AD (e.g., cholinesterase
inhibitors, memantine)

– Current daily use of systemic corticosteroids

– Current use of 3 or more doses of narcotics/week. Use of intermittent narcotics should
be stopped 48 hours prior to clinic visits/cognitive testing. Tramadol is allowed as
long as the dose remains stable for 3 months.

– Use of psychoactive medications, including benzodiazepines, tricyclic antidepressants,
antipsychotics, mood-stabilizers, psychostimulants, anti-parkinsonian medications,
anticonvulsant medications or medications with significant central anticholinergic
activity are allowed as long as the medication is NOT used to treat an exclusionary
medical condition.

– Significant cardiovascular disease (including NYHA 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 (>3 mm) 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 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; intermittent use of corticosteroids or supplemental oxygen to
treat chronic obstructive pulmonary disease exacerbation is allowed; use of inhaled
steroids for asthma is allowed

– End stage renal disease (e.g., requiring dialysis or as per clinician discretion)

– 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 post-treatment

– 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

– Resides in an assisted living facility or nursing home

– Receives hospice care

– Site PI/Study Clinician discretion regarding medical status, appropriateness of
participation or concern about intervention adherence