Lifestyle Intervention Shows Benefits Beyond Cognition in US POINTER Trial, Highlighting Modifiable Risk Factors for Dementia

A 2-year multicomponent lifestyle intervention previously shown to improve cognition in at-risk adults also enhances blood pressure regulation, reduces sleep apnea events, and may protect against cognitive decline linked to specific Alzheimer disease (AD) biomarkers. The findings, from 3 National Institute on Aging-funded ancillary studies were presetented this week at the Clinical Trials in Alzheiemer's Disease (CTAD) annual meeting in San Diego.

"These studies tell us that the U.S. POINTER lifestyle intervention with structured support has substantial and significant health benefits beyond improving cognition — and the benefits are in areas known to lower risk of cognitive decline and dementia," Maria C. Carrillo, PhD, Alzheimer's Association chief science officer and medical affairs lead, said in a statement. "This positive relationship may multiply the beneficial impact of closely adhering to the structured US POINTER 'recipe.'"

The US POINTER Trial

The US POINTER trial, which published initial results in JAMA last July, tested a structured lifestyle intervention combining regular physical exercise, the MIND diet, computerized cognitive training with social and intellectual activities, and regular health metric reviews with goal-setting sessions. The trial compared 2 delivery formats: a structured intervention with intensive support versus a self-guided approach. Participants in the structured group demonstrated greater improvement in global cognition compared to the self-guided group, reflecting an estimated one to two years of slowed cognitive aging.

Sleep Quality: POINTER-zzz

The POINTER-zzz ancillary study examined sleep outcomes in 780 US POINTER participants using at-home sleep monitoring devices. Nearly 65% of participants had at least mild sleep apnea at baseline.

Participants in the structured intervention experienced a reduction of 1 to 2 respiratory disturbance events per hour of sleep compared to those in the self-guided group.

Sleep disorders are common in older adults and frequently go undetected or untreated, according to the Alzheimer's Association. Poor sleep quality has been linked to cognitive decline, suggesting the sleep may be a modifiable risk factor for AD and other related dementias.

"We are excited about this finding, as it shows that the structured intervention improves not only cognition but also other behaviors that affect brain health, which may increase protection against dementia," Laura D. Baker, PhD, professor of internal medicine and public health sceinces at Wake Forest University School of Medicine and Principal Investigator of the sleep ancillary study.

Neurovascular Function: POINTER-NV

The POINTER-NV study enrolled 491 participants who underwent comprehensive vascular health testing at baseline, month 12, and month 24. Researchers used ultrasound and continuous blood pressure monitoring to assess blood vessel structure and function throughout the body and brain.

The structured intervention produced significant improvements in cardiovascular response to sudden blood pressure changes, indicating enhanced blood pressure regulation compared to the self-guided group. The intervention also improved multiple measures of blood vessel health in the aorta and carotid arteries.

Principal Investigators Drs. Brinkley and Shaltout noted the structured intervention "can improve the body's ability to regulate blood pressure, which is crucial for proper brain blood flow to the brain."

Brain Biomarker Interactions

POINTER-Neuroimaging represents the first large-scale investigation of lifestyle intervention effects on biological markers of Alzheimer's disease and dementia. The study enrolled roughly 50% of parent trial participants, who underwent MRI and Aβ and tau positron emission tomography (PET) imaging.

Participants with lower hippocampal volume or higher tau protein accumulation gained greater cognitive benefits from the structured intervention compared to those with similar brain changes in the self-guided group. However, amyloid burden did not influence the degree of cognitive benefit.

"Participating in the U.S. POINTER study's structured intervention protected against the negative effects of tau tangle build up or smaller baseline hippocampal volume," said Dr. Susan Landau, Principal Investigator of the neuroimaging study. She noted that amyloid buildup—the primary biomarker defining Alzheimer's disease—did not predict differential response, meaning "people with amyloid build up experience the same benefits from the intervention as those without amyloid."

Clinical Implications

"These studies tell us that the U.S. POINTER lifestyle intervention with structured support has substantial and significant health benefits beyond improving cognition — and the benefits are in areas known to lower risk of cognitive decline and dementia," said Maria C. Carrillo, PhD, Alzheimer's Association chief science officer.

NIA Director Dr. Richard Hodes stated: "I am very encouraged by these early findings from the U.S. POINTER ancillary studies, which offer valuable insights into the physiological mechanisms that may have contributed to the positive results of the U.S. POINTER trial."

The ancillary studies received funding through the following NIH grants: POINTER-zzz (R01AG064440), POINTER-NV (R01AG066910), POINTER-Neuroimaging (R01AG062689), and POINTER-Microbiome (U19AG063744). A fourth ancillary study examining microbiome changes presented a poster at CTAD 2025, with full results pending.