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

Prior treatment

• 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.
• Currently receiving physical therapy or cardiopulmonary rehabilitation

Other illness

• 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 Diagnostic and Statistical Manual (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)
• 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 New York Heart Association (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 transient ischemic attack (TIA) or small vessel stroke in the last 6 months; TIA occurring more than 6 months ago with residual effects
• 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)
• 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; long-term endocrine therapy for breast cancer is allowed (e.g., tamoxifen, anastrozole)
• History of hip fracture, joint replacement, or spinal surgery in the last 6 months
• History of a malabsorptive bariatric procedure (gastric bypass, biliopancreatic diversion); other bariatric procedures involving restriction (i.e., sleeve, band) are not exclusionary

Lab values

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

Age

• Age \<60 or ≥80 years

Other

• 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

• Sedentary (not a regular exerciser, determined using the POINTER--modified Telephone Assessment of Physical Activity \[TAPA\]
• Low MIND Diet score (determined using the MIND Diet Screener)
• No cognitive impairment as per Telephone Interview for Cognitive Status (mTICS) 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 point: Suboptimum cardiovascular health (treated or untreated): systolic Blood Pressure \>125 mmHg \~OR\~ low-density lipoprotein (LDL) cholesterol \>115 mg/dL\~OR\~ glycated hemoglobin (HbA1c) \>6.0%1 point: First degree family history (mother, father, sister, brother) of memory impairment- 1 point: Race and ethnicity: African American/Black, Native American, Middle Eastern/North African, or Hispanic/Latinx
  • 1 point: Older age: 70-79 years 1 point: Sex: male
• 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
• Capacity to complete physical exercise
• Willing to complete all study-related activities for at least 24 months
• Willing to be randomized to either lifestyle intervention group