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 (NIA)-funded ancillary studies were presetented this week at the Clinical Trials in Alzheiemer's Disease (CTAD) annual meeting in San Diego.1

"These studies tell us that the US 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.'"1

The US POINTER Trial

The US POINTER trial, which published initial results in JAMA last July,2 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.2,3

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.4

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, according to the Alzheimer's Association.1

Sleep disorders are common in older adults and frequently go undetected or untreated. 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.1

Neurovascular Function: POINTER-NV

The POINTER-NV study enrolled 491 parent tiral 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.5

The structured lifestyle 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.1

Poor bloodflow to the brain is a hallmark of AD, the assocation noted, but research on how vascular health is related to regulation of bloodflow has been lacking. A large proportion of POINTER participants had documented athersclerosis, ateriosclerosis, and postural hypotension at baseline.1

The observed improvement in blood pressure regulation not only enhances blood circulation to the brain, "Improved blood pressure regulation can also reduce aging-related vascular changes that allow harmful, pulsing flow of blood — too fast and too much— into the brain," ancillary study principal investigators Tina Brinkley, PhD and Hossam Shaltout, PhD, said in the statement.1

Brain Biomarkers: POINTER-Neuroimaging

POINTER-Neuroimaging6,7 represents the first large-scale investigation of the effects of lifestyle intervention on biological markers of AD and dementia, the Alzhiemer's Association said.1 Participants from the 5 main study sites were invited to participate, with approximately 50% of parent trial participants undergoing MRI and Aβ and tau PET imaging. Investigators evaluated intervention impact on brain health as measured by brain imaging biomarkers of AD and cerebrovascular disease and related cognitive benefits.6,7

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, researchers reported at CTAD. However, amyloid burden did not influence the degree of cognitive benefit.1

"Participating in the US POINTER study's structured intervention protected against the negative effects of tau tangle build up or smaller baseline hippocampal volume," University of California Berkeley's Susan Landau, PhD, PI of the neuroimaging study, said. She noted that amyloid buildup, which is the primary biomarker defining AD, did not predict differential response, meaning "people with amyloid build up experience the same benefits from the intervention as those without amyloid."1

"I am very encouraged by these early findings...which offer valuable insights into the physiological mechanisms that may have contributed to the positive results of the US POINTER trial," NIA Director Richard Hodes, MD, said.1 "The forthcoming publications and continued analysis of this rich dataset will deepen our understanding of how multimodal interventions can support brain health."

"Bottom line, we now have a more comprehensive picture of how the US POINTER intervention affects brain health, and overall health, too," Alzheimer's Association chief science officer and medical lead Carrillo, added.1

A fourth ancillary study examining microbiome changes presented a poster at CTAD 2025, with full results pending.

References

1. The U.S. POINTER structured healthy lifestyle program—previously shown to improve cognition—may also improve sleep apnea, blood pressure regulation, and cognitive resilience. News release. The Alzheimer's Association. December 2, 2025. Accessed December 3, 2025. https://www.prnewswire.com/news-releases/the-us-pointer-structured-healthy-lifestyle-program--previously-shown-to-improve-cognition--may-also-improve-sleep-apnea-blood-pressure-regulation-and-cognitive-resilience-302629883.html

2. Baker LD, Espeland MA, Whitmer RA, et al. Structured vs self-guided multidomain lifestyle interventions for global cognitive function: the US POINTER randomized clinical trial. JAMA. 2025;334(8):681-691. doi:10.1001/jama.2025.12923

3. Jennings S. Structured lifestyel program yields statistically signficant cognitive gains in US POINTER trial. Patient Care. August 4, 2025. Accessed December 3, 2025. https://www.patientcareonline.com/view/structured-lifestyle-program-yields-statistically-significant-cognitive-gains-in-us-pointer-trial

4. Hayden KM, Ingraham B, Beavers DP, et al. POINTER-zzz: study design and baseline characteristics from the U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) sleep ancillary. Alzheimers Dement. 2023;19(S17):e072514. doi:10.1002/alz.072514

5. Brinkley TE, Garcia KR, Mitchell GF, et al. The U.S. POINTER neurovascular ancillary study: study design and methods. Alzheimers Dement. Published online February 24, 2025. doi:10.1002/alz.14574

6. Harrison TM, Ward T, Taggett J, et al. The POINTER imaging baseline cohort: associations between multimodal neuroimaging biomarkers, cardiovascular health, and cognition. Alzheimers Dement. Published online December 3, 2024. doi:10.1002/alz.14374

7. Lockhart SN, Baker LD, Carrillo MC, et al. U.S. POINTER imaging: study design and launch. Alzheimers Dement. 2020;16(S10):e038414. doi:10.1002/alz.038414