Physical frailty in older persons is associated with Alzheimer disease pathology
Abstract
Objective: We examined the extent to which physical frailty in older persons is associated with common age-related brain pathology, including cerebral infarcts, Lewy body pathology, and Alzheimer disease (AD) pathology.
Methods: We studied brain autopsies from 165 deceased participants from the Rush Memory and Aging Project, a longitudinal clinical–pathologic study of aging. Physical frailty, based on four components, including grip strength, time to walk 8 feet, body composition, and fatigue, was assessed at annual clinical evaluations. Multiple regression analyses were used to examine the relation of postmortem neuropathologic findings to frailty proximate to death, controlling for age, sex, and education.
Results: The mean age at death was 88.1 years (SD = 5.7 years). The level of AD pathology was associated with frailty proximate to death (
= 0.252, SE = 0.077, p = 0.001), accounting for 4% of the variance of physical frailty. Neither cerebral infarcts ( = −0.121, SE = 0.115, p = 0.294) nor Lewy body disease pathology ( = 0.07, SE = 0.156, p = 0.678) was associated with frailty. These associations were unchanged after controlling for the time interval from last clinical evaluation to autopsy. The association of AD pathology with frailty did not differ by the presence of dementia, and this association was unchanged even after considering potential confounders, including physical activity; parkinsonian signs; pulmonary function; or history of chronic diseases, including vascular risk factors, vascular disease burden, falls, joint pain, or use of antipsychotic or antihypertensive medications.
= 0.252, SE = 0.077, p = 0.001), accounting for 4% of the variance of physical frailty. Neither cerebral infarcts ( = −0.121, SE = 0.115, p = 0.294) nor Lewy body disease pathology ( = 0.07, SE = 0.156, p = 0.678) was associated with frailty. These associations were unchanged after controlling for the time interval from last clinical evaluation to autopsy. The association of AD pathology with frailty did not differ by the presence of dementia, and this association was unchanged even after considering potential confounders, including physical activity; parkinsonian signs; pulmonary function; or history of chronic diseases, including vascular risk factors, vascular disease burden, falls, joint pain, or use of antipsychotic or antihypertensive medications.Conclusion: Physical frailty in old age is associated with Alzheimer disease pathology in older persons with and without dementia.
Get full access to this article
View all available purchase options and get full access to this article.
REFERENCES
1.
Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146–M156.
2.
Ferrucci L, Guralnik JM, Studenski S, et al. Designing randomized, controlled trials aimed at preventing or delaying functional decline and disability in frail, older persons: a consensus report J Am Geriatr Soc 2004;52:625–634.
3.
Andrews AW, Bohannon RW. Short-term recovery of limb muscle strength after acute stroke. Arch Phys Med Rehabil 2003;84:125–130.
4.
Burn DJ, Rowan EN, Allan LM, et al. Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2006;77:585–589.
5.
Stewart R, Masaki K, Xue Q-L, et al. A 32-year prospective study of change in body weight and incident dementia: the Honolulu-Asia Aging Study. Arch Neurol 2005;62:55–60.
6.
Rosano C, Simonsick EM, Harris TB, et al. Association between physical and cognitive function in healthy elderly: the Health, Aging and Body Composition Study. Neuroepidemiology 2005;24:8–14.
7.
Wang L, Larson EB, Bowen JD, et al. Performance-based physical function and future dementia in older people. Arch Intern Med 2006;166:1115–1120.
8.
Bennett DA, Schneider JA, Buchman AS, et al. The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort. Neuroepidemiology 2005;25:163–175.
9.
Bennett DA, Schneider JA, Aggarwal NT, et al. Decision rules guiding the clinical diagnosis of Alzheimer's disease in two community-based cohort studies compared to standard practice in a clinic-based cohort study. Neuroepidemiology 2006;27:169–176.
10.
Louis ED, Tang MX, Schupf N, et al. Functional correlates and prevalence of mild parkinsonian signs in a community population of older people. Arch Neurol 2005;62:297–302.
11.
Schupf N, Tang MX, Albert SM, et al. Decline in cognitive and functional skills increases mortality risk in nondemented elderly. Neurology 2005;65:1218–1226.
12.
Onder G, Penninx BW, Lapuerta P, et al. Change in physical performance over time in older women: the Women's Health and Aging Study. J Gerontol A Biol Sci Med Sci 2002;57:M289–M293.
13.
Buchman AS, Wilson RS, Bienias JL, et al. Change in frailty and risk of death in older persons. Exp Aging Res (in press).
14.
Buchman AS, Boyle PA, Wilson RS, et al. Frailty is associated with incident Alzheimer's disease and cognitive decline in the elderly. Psychosom Med 2007;69:483–489.
15.
McPhillips JB, Pellettera KM, Barrett-Connor E, et al. Exercise patterns in a population of older adults. Am J Prev Med 1989;5:65–72.
16.
Buchman AS, Wilson RS, Boyle PA, et al. Physical activity and leg strength predict decline in mobility performance in older persons. J Am Geriatr Soc 2007;55:1618–1623.
17.
Boyle PA, Wilson RS, Aggarwal NT, et al. Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology 2006;67:441–445.
18.
Bennett DA, Schneider JA, Tang Y, et al. The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study. Lancet Neurol 2006;5:406–412.
19.
Schneider JA, Boyle PA, Arvanitakis Z, et al. Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons. Ann Neurol 2007;62:59–66.
20.
Wilson RS, Scherr PA, Schneider JA, et al. Relation of cognitive activity and risk of developing Alzheimer disease. Neurology 2007;69:1911–1920.
21.
Schneider JA, Bienias JL, Gilley DW, et al. Improved detection of substantia nigra pathology in Alzheimer's disease. J Histochem Cytochem 2002;50:99–106.
22.
Collett D. Modelling Survival Data in Medical Research, 2nd ed. Boca Raton, FL: Chapman & Hall, 2003.
23.
SAS. SAS/STAT® User's Guide, Version 8, 8th ed. Cary, NC: SAS Institute Inc., 2000.
24.
Walston J, Hadley EC, Ferrucci L, et al. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc 2006;54:991–1001.
25.
Newman AB, Gottdiener JS, McBurnie MA, et al. Associations of subclinical cardiovascular disease with frailty. J Gerontol A Biol Sci Med Sci 2001;56:M158–M166.
26.
Bennett DA, Schneider JA, Bienias JL, et al. Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology 2005;64:834–841.
27.
Riley KP, Snowdon DA, Markesbery WR. Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study. Ann Neurol 2002;51:567–577.
28.
Guillozet AL., Weintraub S, Mach DC, et al. Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch Neurol 2003;60:729–736.
29.
Buchman AS, Wilson RS, Bienias JL, et al. Change in body mass index and risk of incident Alzheimer disease. Neurology 2005;65:892–897.
30.
Schneider JA, Li JL, Li Y, et al. Substantia nigra tangles are related to gait impairment in older persons. Ann Neurol 2006;59:166–173.
31.
Buchman AS, Wilson RS, Boyle PA, et al. Grip strength and the risk of incident Alzheimer's disease. Neuroepidemiology 2007;29:66–73.
32.
Buchman AS, Schneider JA, Wilson RS, et al. Body mass index in older persons is associated with Alzheimer disease pathology. Neurology 2006;67:1949–1954.
33.
Serrien DJ, Ivry RB, Swinnen SP. The missing link between action and cognition. Prog Neurobiol 2007;82:95–107.
34.
Sweeney JA, Luna B, Keedy SK, et al. fMRI studies of eye movement control: investigating the interaction of cognitive and sensorimotor brain systems. Neuroimage 2007;36:T54–T60.
35.
Thorvaldsson V, Hofer SM, Berg S, et al. Onset of terminal decline in cognitive abilities in non-demented individuals. Neurology (in press).
36.
Vassar R. Caspase-3 cleavage of GGA3 stabilizes BACE: implications for Alzheimer's disease. Neuron 2007;54:671–673.
37.
Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008;57:178–201.
Information & Authors
Information
Published In
Copyright
© 2008.
Publication History
Published online: August 11, 2008
Published in print: August 12, 2008
Authors
Metrics & Citations
Metrics
Citation information is sourced from Crossref Cited-by service.
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
Cited By
- Explore the Role of Frailty as a Contributor to the Association Between AT(N) Profiles and Cognition in Alzheimer’s Disease, Journal of Alzheimer’s Disease, 100, 4, (1333-1343), (2024).https://doi.org/10.3233/JAD-231489
- Alzheimer’s Disease and Related Dementias: A Review of Evidence for Clinical Exercise Physiologists, Journal of Clinical Exercise Physiology, 13, 1, (24-34), (2024).https://doi.org/10.31189/2165-6193-13.1.24
- Predicting Brain Amyloid Status Using the National Institute of Health Toolbox (NIHTB) for Assessment of Neurological and Behavioral Function, The Journal of Prevention of Alzheimer's Disease, 11, 4, (943-957), (2024).https://doi.org/10.14283/jpad.2024.77
- Evaluation of the effects of thyroid functions on frailty in geriatric patients using the Edmonton, SOF and FRAIL Scales, BMC Geriatrics, 24, 1, (2024).https://doi.org/10.1186/s12877-024-05643-5
- Association between frailty and cognitive status among ambulating Korean elderly: An observational study, Medicine, 103, 32, (e39222), (2024).https://doi.org/10.1097/MD.0000000000039222
- Midlife cumulative deficit frailty predicts Alzheimer’s disease-related plasma biomarkers in older adults, Age and Ageing, 53, 3, (2024).https://doi.org/10.1093/ageing/afae028
- New horizons in the diagnosis and management of Alzheimer’s Disease in older adults, Age and Ageing, 53, 2, (2024).https://doi.org/10.1093/ageing/afae005
- Alzheimer’s disease risk reduction in clinical practice: a priority in the emerging field of preventive neurology, Nature Mental Health, 2, 1, (25-40), (2024).https://doi.org/10.1038/s44220-023-00191-0
- Physical frailty, genetic predisposition, and incident dementia: a large prospective cohort study, Translational Psychiatry, 14, 1, (2024).https://doi.org/10.1038/s41398-024-02927-7
- Intake of vegetables and fruits at midlife and the risk of physical frailty in later life, The Journal of nutrition, health and aging, 28, 11, (100374), (2024).https://doi.org/10.1016/j.jnha.2024.100374
- See more
Loading...
View Options
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.
If you need immediate support or to place an order, please call or email customer service:
- 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
- 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
- [email protected]
We appreciate your patience during this time and apologize for any inconvenience.