Association of Physical Function with Clinical and Subclinical Brain Disease: The Framingham Offspring Study

Erica C. Camargo, Galit Weinstein, Alexa S. Beiser, Zaldy S. Tan, Charles Decarli, Margaret Kelly-Hayes, Carlos Kase, Joanne M. Murabito, Sudha Seshadri

Research output: Contribution to journalArticlepeer-review


Background: Handgrip strength and gait speed are simple measures of physical capability and have been associated with current and future health outcomes. However, studies on their associations with brain structure and function in middle-aged adults are lacking. Objective: To assess the relationship of fast-paced walking speed and handgrip strength with risk of dementia, Alzheimer's disease (AD), and stroke, as well as the cross-sectional associations with cognitive and brain magnetic resonance imaging (MRI) measures in a middle-aged community sample. Methods: Framingham Offspring (n=2,176; mean age 62, 54 female) had physical function, brain MRI, and cognitive evaluations between 1999 and 2005 and were followed-up for incident dementia AD and stroke until 11 years later. We related walking speed and handgrip strength to incident dementia, AD, and stroke using Cox models, and to brain and cognitive measures using multivariable linear and logistic regression. Models were adjusted for age, sex, education, and vascular risk factors. Results: Slow walking and weak handgrip were associated with more than 2.5-fold increase in risk of AD. Weaker handgrip was associated with an increased risk of incident stroke (HR 1.74, 95 CI: 1.122.70/SDU, p=0.01) in persons ≥65 years. Both measures were associated with lower total brain volume and poorer performance on tests of visual memory, language, executive function, and visuoperceptual function. Slower gait was also related to poorer verbal memory, and weaker handgrip to poorer abstraction. Conclusion: Tests of walking speed and handgrip strength may serve as clinical markers of brain structure and function and may improve dementia risk prediction.

Original languageEnglish
Pages (from-to)1597-1608
Number of pages12
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - 2016

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS Thisworkwas supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC-25195) and by grants from the National Institutes of Health, National Institute of Neurologic Disorders and Stroke (R01-NS-17950) and from the National Institute on Aging (R01-AG-008122; AG-016495; AG-033193; AG-031287, P30-AG-013846, U01 AG-049505).


  • Alzheimer's disease
  • Brain imaging
  • Cognitive function
  • Dementia
  • Gait
  • Hand strength
  • Observational study
  • Stroke

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Clinical Psychology
  • General Neuroscience


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