Prospects for Clinicians to Reduce Cognitive Decline in Elderly Patients

Cognitive decline is an increasing clinical and public health problem in the United States (US) and globally. Cognitive decline encompasses decreased executive functions, including memory, thinking, and reasoning. Clinicians encounter a range of patients who suffer from cognitive decline. These range from mild cognitive impairment to more severe conditions like Alzheimer’s disease or severe dementia. Today, about 7.2 million Americans age 65 years and older suffer from Alzheimer’s disease. By 2060, this figure is estimated to be 13.8 million.1 These data indicate that, clinicians and public health practitioners face major challenges. The goals of clinicians and public health practitioners are the same which is, namely, to reduce significant cognitive decline as well as mild or moderate declines in their patients. Between 2000 and 2022, death rates from cardiovascular disease, including coronary heart disease, declined, but deaths from Alzheimer’s disease increased by over 142%.1 In addition, it had been estimated in 2020 that perhaps 40 to 45% of the risks of dementia may be attributable to modifiable environmental factors.¹ The strongest known and best described risk factor for cognitive decline is chronological age. Loss of cognition among the elderly, however, is not an inevitable consequence of aging. Lifestyle risk factors such as physical inactivity, unhealthy diets, obesity, alcohol consumption and medical conditions such as dyslipidemias, hypertension, diabetes, and depression as well as social isolation and intellectual inactivity have been postulated to play important roles in cognitive decline.1 The same therapeutic lifestyle changes of proven benefit in cardiovascular diseases and other common serious diseases, including colorectal cancer, each individually has the potential to decrease cognitive decline in elderly patients. Further, it is tempting to speculate that the presence of multiple risk factors may be additive. Thus, therapeutic lifestyle changes, if demonstrated to be beneficial, would have major clinical and public health implications in reducing cognitive decline in the US and worldwide. This possibility is of even greater importance given the interrelationships of cognitive decline with increasing age as well as the increasing proportion of US and other populations of the elderly.

With respect to advancing medical knowledge, there are several known and postulated biological mechanisms that may explain why therapeutic lifestyle changes may reduce cognitive decline.2,3 For example, physical activity improves brain health through a variety of mechanisms. Increased levels of physical activity have been linked to increases in brain-derived neurotrophic factor (BDNF). BDNF supports neuronal growth and remapping, specifically in the hippocampus which is damaged in dementia. In one randomized trial, patients assigned to an aerobic exercise plan demonstrated increased hippocampal volume and improved spatial memory.4 Increases in daily physical activity also improve cerebral perfusion and reduce pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alfa (TNF-α). Both IL-6 and TNF-α have been implicated in neurodegeneration. Dietary patterns such as the Mediterranean as well as DASH diets may reduce oxidative stress, improve insulin sensitivity, and lower vascular risk. Smoking cessation may preserve white matter integrity and reduce the risk of microvascular cognitive impairment. Specifically, cigarette smokers have significantly worse cognitive performance than nonsmokers. Further, in a neuroimaging study, cigarette smokers also have greater evidence of Alzheimer’s disease related changes than their non-smoking counterparts.5 The known as well as postulated mechanisms to explain why therapeutic lifestyle changes may improve cognitive decline in elderly patients provide support for the hypothesis that adoption of therapeutic lifestyle changes will reduce cognitive decline.

Advances in medical knowledge also include the unique contributions of large-scale randomized trials, which, in hypothesis testing, provide the most reliable means to detect the most plausible small to moderate effects of interventions.² ³ The results of the first large scale randomized trial of this issue from the US were presented in late July 2025 at the Alzheimer’s Association International Conference and published simultaneously online in JAMA.6 with an accompanying editorial.7 In the Protect Brain Health Through Lifestyle Interventions to Reduce Risk (POINTER) trial, 2111 men and women aged 60 to 79 years at high risk for cognitive decline due to their risk factors were enrolled. Willing and eligible participants were randomized to either a high intensity lifestyle intervention or a self-guided program. Both randomized groups were made aware of the importance of diet and nutrition, which included emphasis on a combination of the Mediterranean and Dietary Approaches to Stop Hypertension diets. They were also instructed in methods of cognitive stimulation and planned social engagement. The group assigned to the high intensity lifestyle intervention had frequent team meetings in person, professional guidance and accountability measures, whereas the self-guided group received educational materials and general support. After two years, the group assigned to the high intensity lifestyle intervention demonstrated statistically significant and clinically important improvements in global cognition. These findings were strongest in the subgroup of executive functions which include planning, attention, and problem solving.

These findings are consistent with the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial.8 Participants had high scores for cognitive decline as well as cardiovascular disease. Like POINTER, there was a multidomain intervention group, and a comparison group that was assigned general health advice. The primary prespecified outcome was change in cognition measured through a neuropsychological test battery. When compared to those in the comparison group, participants randomized to the intense intervention group had significantly greater improvements in neuropsychological test batteries. Notably, at baseline, participants in the FINGER trial had elevated cardiovascular risk scores.

There are implications for clinical practice, public health, and government policy, as well as further research. Clinicians will now be armed with lifestyle-based changes to reduce cognitive decline. In addition, public health practitioners may also add to their programs based on the study designs of POINTER and FINGER to maintain brain health, complementing pharmacologic approaches. From a policy perspective, these findings include potential cost savings. Among the factors responsible are the expensive costs of the newly developed pharmacologic agents. These agents tend to offer modest benefits but sometimes at the risk of common and sometimes serious side effects. The common side effects include loss of appetite, nausea, vomiting, headache, fatigue and restlessness. The rare but more serious side effects include gastrointestinal bleeding, confusion, agitation, and seizures. In a mathematical modeling study, reduction of risk factors by 10 to 20% per decade would yield an 8 to 15% decline in cognitive loss. The findings also imply that early attention to risk factor modifications may reduce future medical and caregiving costs.¹

Dementia is a disease where the cost of time and resources to family members and caregivers is extremely high. It is estimated that in 2024 nearly 12 million family members and unpaid caregivers committed 19.2 billion hours to those with dementia – corresponding to a societal cost of $413.5 billion.¹ Furthermore, caregiving is associated with emotional stresses and adverse mental health outcomes. These circumstances emphasize the urgent need for clinical, public-health, and community-based interventions to reduce the significant burden of cognitive decline. Finally, there is also a need for more basic, clinical, and epidemiological research.2,3

Thus, the available data strongly support the need for coordinated clinical, public health, and policy measures to implement lifestyle-based interventions aimed to mitigate the rising burden of cognitive loss in the US and globally.