Self-reported measures of limitation in physical function in late midlife are associated with incident Alzheimer's disease and related dementias

Aging Clin Exp Res. 2022 Aug;34(8):1845-1854. doi: 10.1007/s40520-022-02132-w. Epub 2022 Apr 19.


Background: Even small improvements in modifiable Alzheimer's disease and related dementias (ADRD) risk factors could lead to a substantial reduction of dementia cases.

Aims: To determine if self-reported functional limitation associates with ADRD symptoms 4-18 years later.

Methods: We conducted a prospective longitudinal study using the Health and Retirement Study of adults aged 51-59 years in 1998 without symptoms of ADRD by 2002 and followed them to 2016. Main exposure variables were difficulty with activities of daily living, mobility, large muscle strength, gross motor and upper limb activities. The outcome was incident ADRD identified by the Lange-Weir algorithm, death, or alive without ADRD. We fit two GEE multinomial models for each measure: (1) baseline measure of function and (2) change in function over time.

Results: In the model with baseline only and outcome, only difficulty with mobility associated with future ADRD across levels of difficulty with near dose-response effect (risk ratios (RR) difficulty with 1-5 functions respectively, compared with no difficulty: 1.82; 2.70; 1.73 2.81; 4.03). Mobility also significantly associated with ADRD when allowing for change over time among those with 3, 4 or 5 versus no mobility limitations (RR 1.76; 2.36; 2.37).

Discussion: The results infer that an adult in midlife reporting difficulty with mobility as well as those with no mobility limitations in midlife but who later report severe limitations may be at increased risk of incident ADRD.

Conclusions: Self-reported measures of mobility limitation may be early indicators of ADRD and may be useful for public health planning.

Keywords: ADRD; Health and retirement study; Late midlife; Physical function limitation.

MeSH terms

  • Activities of Daily Living
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / epidemiology
  • Dementia* / diagnosis
  • Humans
  • Longitudinal Studies
  • Prospective Studies
  • Self Report
  • United States