The beneficial effects of a structured healthy lifestyle program for older adults go beyond improved cognition to include improved blood pressure regulation, reduced sleep apnea respiratory events, and increased cognitive resilience for those with certain Alzheimer’s disease (AD)-related brain changes.

That’s according to findings from three ancillary studies to the US POINTER trial, presented on December 2 at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) Conference.

“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 news release.

“Bottom line, we now have a more comprehensive picture of how the US POINTER intervention affects brain health, and overall health, too,” Carrillo added.

Positive Topline Ancillary Study Results

As previously reported by Medscape Medical News, two different lifestyle interventions improved cognition over 2 years in older adults at risk for cognitive decline, enrolled in the Alzheimer’s Association’s US POINTER study.

However, the high-intensity, structured intervention with more support and accountability led to significantly greater improvement on global cognition than a less intense, self-guided intervention. Compared with participants in the self-guided group, those in the structured group performed at a level comparable to adults 1-2 years younger in age.

The US POINTER Neurovascular Ancillary Study (POINTER-NV) investigated neurovascular mechanisms that may underlie the structured intervention’s effects on cognitive function and overall brain health.

It included 491 participants from the parent study who completed comprehensive testing of vascular health at baseline and 12 and 24 months.

The primary outcome was baroreflex sensitivity — a measure of the ability of the body to regulate acute changes in blood pressure, which has important implications for cerebral blood flow, Tina Brinkley, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina, explained in her presentation.

The structured intervention group saw a “statistically significant 14% increase in baroreflex sensitivity compared to a very minor, nonsignificant 3% increase in the self-guided group,” Brinkley told attendees. This effect was fairly consistent across subgroups.

The structured intervention was also associated with significant improvements in heart rate variability and vascular hemodynamics.

Susan Landau, PhD, with University of California Berkeley presented results of the US POINTER Neuroimaging Ancillary Study — the first large-scale investigation of how lifestyle interventions affect biological markers of AD and dementia in the brain.

It included 983 original trial participants who underwent MRI at baseline and 12 and 24 months and amyloid-beta and tau PET imaging at baseline and 24 months.

Overall, there were no differences between the two intervention groups on 2-year change in amyloid-beta or entorhinal tau PET, hippocampal volume or white matter hyperintensity volume, Landau reported. However, longer follow-up time may be needed to detect biomarker changes, she noted.

In subgroup analyses, participants with “at-risk” imaging profiles — lower baseline hippocampal volume or greater entorhinal tau accumulation — had greater cognitive benefits from the structured lifestyle intervention than those with these brain changes in the self-guided group.

“Participating in the US POINTER study’s structured intervention protected against the negative effects of tau tangle build up or smaller baseline hippocampal volume,” Landau said in a statement.

Laura Baker, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina, presented results of US POINTER Sleep Ancillary Study (POINTER-zzz) — which revealed a significant decline in respiratory disturbances during sleep in the structured intervention group relative to the self-guided group.

Sleep disorders are highly prevalent in older adults, often go undetected and untreated, and are associated with poor brain health outcomes, including cognitive decline, Baker explained.

Of the 780 adults who participated POINTER-zzz ancillary study, 42% had mild sleep apnea (Apnea-Hypopnea Index [AHI], 5 to < 15), 17% had moderate sleep apnea (AHI, 15 to < 30), and 4% had severe sleep apnea (AHI, > 30) at baseline.

Compared with the self-guided group, the number of sleep apnea events declined by 1-2 per hour of sleep in the structured intervention group, independent of baseline BMI. “If we’re assuming 6 hours of sleep, that’s about 10 of those significant respiratory events per night, 365 days a week,” Baker told attendees.

These results were consistent across several key subgroups and tended to be stronger in adults with more severe baseline sleep apnea.

In addition, actigraphy data showed significant sleep fragmentation among study participants. Wake after sleep onset — that is the number of minutes awake during an entire night of sleep — was 77.5 minutes in the structured group and 81.0 minutes in the self-guided group. “Typical is 30-60 minutes — so anything above 70 is clinically significant,” Baker noted.

Analyses of the sleep fragmentation data and the impact of the interventions is ongoing and was not reported.

Baker said the team still has extensive data to examine, both within the sleep study, but also in relation to the brain imaging and neurovascular data — as well as gut microbiome data, which is being collected in a fourth ancillary study from US POINTER.

The hope, said Baker, is that improved sleep due to a lifestyle intervention may increase neuroprotection and reduce the risk for cognitive decline via reduced hypoxic burden, increased sleep continuity, and stabilized cerebral blood flow and clearance of neurotoxins.

In a statement, Richard Hodes, MD, director of the National Institute on Aging (NIA), said he is “very encouraged” by these early findings from the ancillary studies, “which offer valuable insights into the physiological mechanisms that may have contributed to the positive results of the US POINTER trial.”

“The forthcoming publications and continued analysis of this rich dataset will deepen our understanding of how multimodal interventions can support brain health,” Hodes added.

The Alzheimer’s Association provided funding for the main US POINTER trial. The NIA funded the ancillary studies. The authors had no relevant disclosures.