# Long-term impact of random assignment to intensive lifestyle intervention on Alzheimers disease and related dementias: The Action for Health in Diabetes ADRD Study (Look AHEAD-MIND)

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $1,041,032

## Abstract

It is critical to understand the role of lifestyle intervention for the treatment of older adults with type 2 diabetes
mellitus and obesity. Together, these two diseases nearly double one's risk for Alzheimer's disease and related
dementias. The Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial documented
that 10 years of intensive lifestyle intervention to reduce caloric intake and increase physical activity was
associated with a 30% decrease in the odds of Alzheimer's disease, related dementias, and mild cognitive
impairment in overweight older adults with type 2 diabetes. However, power was limited to establish this
potential benefit firmly [95% CI for odds ratio: 0.40-1.22]. If this finding holds, it provides a powerful message to
support lifestyle interventions in this rapidly growing population. Disturbingly, this intervention was not uniformly
beneficial for all adults. Look AHEAD also reported that among the 837 individuals with the greatest level of
obesity, e.g. body mass index >40 kg/m2, the intensive lifestyle intervention appeared to increase the odds of
Alzheimer's disease, related dementias, and mild cognitive impairment by a factor of 1.46 [0.83-2.56]. Cerebral
blood flow data in this cohort point towards an impaired neurovascular response as the underlying mechanism
for these harmful effects. However, more data are needed to establish these findings and to identify more
firmly the mechanisms underlying the potential benefits and harms that have been observed. Look AHEAD, the
only long-term randomized trial of lifestyle intervention in persons with type 2 diabetes, provides the
unprecedented and timely opportunity to assess the legacy that a successful, sustained, and well-documented
lifestyle intervention has on cognitive resilience and the risk of Alzheimer's disease, related dementia, and mild
cognitive impairment in a large and diverse cohort drawn from clinical centers across the US.
 The Action for Health in Diabetes Alzheimer's Disease and Related Dementias Study (Look AHEAD-MIND)
that we propose will answer the question of whether interventions designed to induce and sustain long term
weight losses lead to cognitive benefit in some, or harm in others, and determine the role that baseline weight
plays in modifying this association. We propose to repeat the cognitive assessment and adjudication of
cognitive impairment in the cohort (N=3,500), more than doubling the number of cases: to confirm findings and
identify potential mechanisms for benefit (inflammation, sex hormones) and harm (angiogenesis). Combining
the rich characterization of the Look AHEAD cohort over nearly 20 years with these incident cases and
cognitive trajectories (two-thirds of the cohort has had only one cognitive assessment), we will identify factors
related to cognitive resilience. We will also develop public-use databases to promote research on cognitive
health in the rapidly growing and understudied population of older in...

## Key facts

- **NIH application ID:** 10168411
- **Project number:** 5R01AG058571-04
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MARK Andrew ESPELAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,041,032
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168411

## Citation

> US National Institutes of Health, RePORTER application 10168411, Long-term impact of random assignment to intensive lifestyle intervention on Alzheimers disease and related dementias: The Action for Health in Diabetes ADRD Study (Look AHEAD-MIND) (5R01AG058571-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10168411. Licensed CC0.

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