Frailty-a risk factor of global and domain-specific cognitive decline among a nationally representative sample of community-dwelling older adult U.S. Medicare beneficiaries.

OBJECTIVES frail older adults may be more vulnerable to stressors, resulting in steeper declines in cognitive function. Whether the frailty-cognition link differs by cognitive domain remains unclear; however, it could lend insight into underlying mechanisms. METHODS we tested whether domain-specific cognitive trajectories (clock-drawing test, (CDT), immediate and delayed recall, orientation to date, time, president and vice-president naming) measured annually (2011-2016) differ by baseline frailty (physical frailty phenotype) in the National Health and Aging Trends Study (n = 7,439), a nationally representative sample of older adult U.S. Medicare beneficiaries, using mixed effects models to describe repeated measures of each cognitive outcome. To determine if the association between frailty and subsequent cognitive change differed by education, we tested for interaction using the Wald test. RESULTS we observed steeper declines for frail compared to non-frail participants in each domain-specific outcome, except for immediate recall. Largest differences in slope were observed for CDT (difference = -0.12 (standard deviations) SD/year, 95%CI: -0.15, -0.08). By 2016, mean CDT scores for frail participants were 1.8 SD below the mean (95%CI: -1.99, -1.67); for non-frail participants, scores were 0.8 SD below the mean (95%CI: -0.89, -0.69). Associations differed by education for global cognitive function (Pinteraction < 0.001) and for each domain-specific outcome: CDT (Pinteraction < 0.001), orientation (Pinteraction < 0.001), immediate (Pinteraction < 0.001) and delayed (Pinteraction < 0.001) word recalls. CONCLUSION frailty is associated with lower levels and steeper declines in cognitive function, with strongest associations for executive function. These findings suggest that aetiologies are multifactorial, though primarily vascular related; further research into its association with dementia sub-types and related pathologies is critical.

[1]  A. Gross,et al.  Physical Frailty Phenotype Criteria and their Synergistic Association on Cognitive Functioning. , 2020, The journals of gerontology. Series A, Biological sciences and medical sciences.

[2]  Jing Tian,et al.  U.S. National Profile of Older Adults with Cognitive Impairment Alone, Physical Frailty Alone, and Both , 2020, Journal of the American Geriatrics Society.

[3]  R. Varadhan,et al.  Principles and Issues for Physical Frailty Measurement and its Clinical Application. , 2019, The journals of gerontology. Series A, Biological sciences and medical sciences.

[4]  Jing Tian,et al.  Hierarchical Development of Frailty and Cognitive Impairment: Clues into Etiological Pathways. , 2019, The journals of gerontology. Series A, Biological sciences and medical sciences.

[5]  J. Walston,et al.  Frailty Screening and Interventions: Considerations for Clinical Practice. , 2018, Clinics in geriatric medicine.

[6]  Silvina Santana,et al.  Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults: a systematic review , 2018, JBI database of systematic reviews and implementation reports.

[7]  H. Wunsch,et al.  A Scoping Review of Frailty and Acute Care in Middle-Aged and Older Individuals with Recommendations for Future Research , 2017, Canadian geriatrics journal : CGJ.

[8]  Jenny Ploeg,et al.  Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a scoping review of the literature and international policies , 2017, Age and ageing.

[9]  R. Varadhan,et al.  Declines and Impairment in Executive Function Predict Onset of Physical Frailty. , 2016, The journals of gerontology. Series A, Biological sciences and medical sciences.

[10]  Job G. Godino,et al.  Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments , 2016, Ageing Research Reviews.

[11]  R. Varadhan,et al.  Frailty in Older Adults: A Nationally Representative Profile in the United States. , 2015, The journals of gerontology. Series A, Biological sciences and medical sciences.

[12]  D. Segev,et al.  Changes in Frailty After Kidney Transplantation , 2015, Journal of the American Geriatrics Society.

[13]  Allan Gustavo Brigola,et al.  Relationship between cognition and frailty in elderly: A systematic review , 2015, Dementia & neuropsychologia.

[14]  M. Cesari,et al.  Frailty and cognitive decline: how do they relate? , 2015, Current opinion in clinical nutrition and metabolic care.

[15]  V. Pankratz,et al.  Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal , 2014, Neurology.

[16]  David S Knopman,et al.  Classification and epidemiology of MCI. , 2013, Clinics in geriatric medicine.

[17]  G. Savva,et al.  Frailty and cognitive impairment—A review of the evidence and causal mechanisms , 2013, Ageing Research Reviews.

[18]  C. Jack,et al.  Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers , 2013, The Lancet Neurology.

[19]  N. Doba,et al.  A pilot trial to predict frailty syndrome: The Japanese Health Research Volunteer Study , 2012, Experimental Gerontology.

[20]  Jenny Lee,et al.  Physical frailty predicts future cognitive decline — A four-year prospective study in 2737 cognitively normal older adults , 2011, The journal of nutrition, health & aging.

[21]  Jennifer C Cornman,et al.  Validation of new measures of disability and functioning in the National Health and Aging Trends Study. , 2011, The journals of gerontology. Series A, Biological sciences and medical sciences.

[22]  A. Mitnitski,et al.  Transitions in cognitive status in relation to frailty in older adults: A Comparison of three frailty measures , 2011, The journal of nutrition, health & aging.

[23]  Denise C. Park,et al.  Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[24]  Q. Xue The frailty syndrome: definition and natural history. , 2011, Clinics in geriatric medicine.

[25]  G. Ostir,et al.  Cognitive status and future risk of frailty in older Mexican Americans. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[26]  Kenneth J Ottenbacher,et al.  Relationship Between Frailty and Cognitive Decline in Older Mexican Americans , 2008, Journal of the American Geriatrics Society.

[27]  Donald R. Miller,et al.  patients' Self‐report of Diseases in the Medicare Health Outcomes Survey Based on Comparisons With Linked Survey and Medical Data From the Veterans Health Administration , 2008, The Journal of ambulatory care management.

[28]  Y. Rolland,et al.  Frailty: toward a clinical definition. , 2008, Journal of the American Medical Directors Association.

[29]  A. Mitnitski,et al.  Frailty in relation to the accumulation of deficits. , 2007, The journals of gerontology. Series A, Biological sciences and medical sciences.

[30]  L. Ferrucci,et al.  Phenotype of frailty: characterization in the women's health and aging studies. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[31]  I. McDowell,et al.  A global clinical measure of fitness and frailty in elderly people , 2005, Canadian Medical Association Journal.

[32]  D. W. Desmond,et al.  The neuropsychology of vascular cognitive impairment: is there a specific cognitive deficit? , 2004, Journal of the Neurological Sciences.

[33]  R. Petersen Mild cognitive impairment as a diagnostic entity , 2004, Journal of internal medicine.

[34]  L. Ferrucci,et al.  Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[35]  J. Thornby,et al.  Is Mild Cognitive Impairment Prodromal for Vascular Dementia Like Alzheimer’s Disease? , 2002, Stroke.

[36]  Y. Stern What is cognitive reserve? Theory and research application of the reserve concept , 2002, Journal of the International Neuropsychological Society.

[37]  J. Schneider,et al.  Participation in cognitively stimulating activities and risk of incident Alzheimer disease. , 2002, JAMA.

[38]  Kenneth Rockwood,et al.  Accumulation of Deficits as a Proxy Measure of Aging , 2001, TheScientificWorldJournal.

[39]  L. Fried,et al.  Frailty in older adults: evidence for a phenotype. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[40]  K. Shulman,et al.  Clock‐drawing and dementia in the community: A longitudinal study , 1993 .

[41]  J. Morris,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer's disease , 1989, Neurology.

[42]  H. Chui,et al.  10-minute delayed recall from the modified mini-mental state test predicts Alzheimer's disease pathology. , 2014, Journal of Alzheimer's disease : JAD.

[43]  Robert C Green,et al.  Clock drawing test ratings by dementia specialists: interrater reliability and diagnostic accuracy. , 2010, The Journal of neuropsychiatry and clinical neurosciences.