Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2015

Open Access 01-12-2015 | Research

Cumulative impact of health deficits, social vulnerabilities, and protective factors on cognitive dynamics in late life: a multistate modeling approach

Authors: Joshua J Armstrong, Arnold Mitnitski, Melissa K Andrew, Lenore J Launer, Lon R White, Kenneth Rockwood

Published in: Alzheimer's Research & Therapy | Issue 1/2015

Login to get access

Abstract

Introduction

Many factors influence late-life cognitive changes, and evaluating their joint impact is challenging. Typical approaches focus on average decline and a small number of factors. We used multistate transition models and index variables to look at changes in cognition in relation to frailty (accumulation of health deficits), social vulnerability, and protective factors in the Honolulu-Asia Aging Study (HAAS).

Methods

The HAAS is a prospective cohort study of 3,845 men of Japanese descent, aged 71 to 93 years at baseline. Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI). Baseline index variables were constructed of health deficits (frailty), social vulnerabilities, and protective factors. The chances of improvement/stability/decline in cognitive function and death were simultaneously estimated using multistate transition modeling for 3- and 6-year transitions from baseline.

Results

On average, CASI scores declined by 5.3 points (standard deviation (SD) = 10.0) over 3 years and 9.5 points (SD = 13.9) over 6 years. After adjusting for education and age, baseline frailty was associated with an increased risk of cognitive decline at 3 years (β = 0.18, 95% confidence interval (CI), 0.08 to 0.29) and 6 years (β = 0.40, 95% CI, 0.27 to 0.54). The social vulnerability index was associated with 3-year changes (β = 0.16, 95% CI, 0.09 to 0.23) and 6-year changes (β = 0.14, 95% CI, 0.05 to 0.24) in CASI scores. The protective index was associated with reductions in cognitive decline over the two intervals (3-year: β = −0.16, 95% CI, −0.24 to −0.09; 6-year: β = −0.21, 95% CI, −0.31 to –0.11,).

Conclusions

Research on cognition in late life needs to consider overall health, the accumulation of protective factors, and the dynamics of cognitive change. Index variables and multistate transition models can enhance understanding of the multifactorial nature of late-life changes in cognition.
Appendix
Available only for authorised users
Literature
1.
Wilson RS, Beckett LA, Barnes LL, Schneider JA, Bach J, Evans DA, et al. Individual differences in rates of change in cognitive abilities of older persons. Psychol Aging. 2002;17:179–93.CrossRefPubMed
2.
Yaffe K, Fiocco AJ, Lindquist K, Vittinghoff E, Simonsick EM, Newman AB, et al. Predictors of maintaining cognitive function in older adults: The Health ABC Study. Neurology. 2009;72:2029–35.CrossRefPubMedCentralPubMed
3.
Mitnitski A, Fallah N, Wu YG, Rockwood K, Borenstein AR. Changes in cognition during the course of eight years in elderly Japanese Americans: a multistate transition model. Ann Epidemiol. 2010;20:480–6.CrossRefPubMed
4.
Hayden KM, Reed BR, Manly JJ, Tommet D, Pietrzak RH, Chelune GJ, et al. Cognitive decline in the elderly: an analysis of population heterogeneity. Age Ageing. 2011;40:684–9.CrossRefPubMedCentralPubMed
5.
Artero S, Ancelin M, Portet F, Dupuy A, Berr C, Dartigues JF, et al. Risk profiles for mild cognitive impairment and progression to dementia are gender specific. J Neurol Neurosurg Psychiatry. 2008;79:979–84.CrossRefPubMed
6.
Matthews FE, Stephan BCM, McKeith IG, Bond J, Brayne C. Two-year progression from mild cognitive impairment to dementia: to what extent do different definitions agree? J Am Geriatr Soc. 2008;56:1424–33.CrossRefPubMed
7.
Ganguli M, Snitz BE, Saxton JA, Chang CC, Lee CW, Vander Bilt J, et al. Outcomes of mild cognitive impairment by definition: a population study. Arch Neurol. 2011;68:761–7.PubMedCentralPubMed
8.
Brodaty H, Heffernan M, Kochan NA, Draper B, Trollor JN, Reppermund S, et al. Mild cognitive impairment in a community sample: The Sydney Memory and Ageing Study. Alzheimers Dement. 2013;9:310–7. e1.CrossRefPubMed
9.
Sachdev P, Lipnicki D, Crawford J, Reppermund S, Kochan NA, Trollor JN, et al. Sydney Memory Ageing Study Team. Factors predicting reversion from mild cognitive impairment to normal cognitive functioning: a population-based study. PLoS One. 2013;8:e59649.CrossRefPubMedCentralPubMed
10.
Hsiung G, Donald A, Grand J, Black S, Bouchard R, Gauthier S, et al. Outcomes of cognitively impaired not demented at 2 years in the Canadian cohort study of cognitive impairment and related dementias. Dement Geriatr Cogn Disord. 2006;22:413–20.CrossRefPubMed
11.
Roberts R, Knopman D, Mielke M, Cha RH, Pankratz VS, Christianson TJ, et al. Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal. Neurology. 2014;82:317–25.CrossRefPubMedCentralPubMed
12.
Koepsell T, Monsell S. Reversion from mild cognitive impairment to normal or near-normal cognition: risk factors and prognosis. Neurology. 2012;79:1591–8.CrossRefPubMedCentralPubMed
13.
Lopez OL, Becker JT, Chang YF, Sweet RA, Dekosky ST, Gach MH, et al. Incidence of mild cognitive impairment in the Pittsburgh cardiovascular health study-cognition study. Neurology. 2012;79:1599–606.CrossRefPubMedCentralPubMed
14.
Mitnitski A, Fallah N, Dean CB, Rockwood K. A multi-state model for the analysis of changes in cognitive scores over a fixed time interval. Stat Methods Med Res. 2014;23:244–56.CrossRef
15.
Mitnitski A, Fallah N, Rockwood K. A multistate model of cognitive dynamics in relation to frailty in older adults. Ann Epidemiol. 2011;21:507–16.CrossRefPubMed
16.
Song X, Mitnitski A, Zhang N, Chen W, Rockwood K. Alzheimer’s Disease Neuroimaging Initiative. Dynamics of brain structure and cognitive function in the Alzheimer’s disease neuroimaging initiative. J Neurol Neurosurg Psychiatry. 2013;84:71–8.CrossRefPubMed
17.
White L, Petrovitch H, Ross W, Masaki KH, Abbottt RD, Teng EL, et al. Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study. JAMA. 1996;276:955–60.CrossRefPubMed
18.
Teng EL, Hasegawa K, Homma A, Imai Y, Larson E, Graves A, et al. The Cognitive Abilities Screening Instrument (CASI): a practical test for cross-cultural epidemiological studies of dementia. Int Psychogeriatr. 1994;6:45.CrossRefPubMed
19.
Graves A, Larson E, Kukull W, White L, Teng E. Screening for dementia in the community in cross national studies: comparison between the Cognitive Abilities Screening Instrument and the Minimental State Examination. In: Corain B, Iqbal K, Nicolini M, et al., editors. Alzheimer’s Disease: Advances in Clinical and Basic Research. New York: John Wiley & Sons; 1993. p. 113–9.
20.
Gelber R, Launer L, White L. The Honolulu-Asia Aging Study: epidemiologic and neuropathologic research on cognitive impairment. Curr Alzheimer Res. 2012;9:664–72.CrossRefPubMed
21.
22.
23.
Andrew MK, Rockwood K. Social vulnerability predicts cognitive decline in a prospective cohort of older Canadians. Alzhimers Dement. 2010;6:319–25.CrossRef
24.
Wang C, Song X, Mitnitski A, Fang X, Tang Z, Yu P, et al. Effect of health protective factors on health deficit accumulation and mortality risk in older adults in the Beijing Longitudinal Study of Aging. J Am Geriatr Soc. 2014;62:821–8.CrossRefPubMed
25.
Middleton L, Barnes D, Lui L, Yaffe K. Physical activity over the life course and its association with cognitive performance and impairment in old age. J Am Geriatr Soc. 2010;58:1322–6.CrossRefPubMedCentralPubMed
26.
Gow AJ, Bastin ME, Muñoz Maniega S, Valdés Hernández MC, Morris Z, Murray C, et al. Neuroprotective lifestyles and the aging brain: activity, atrophy, and white matter integrity. Neurology. 2012;79:1802–8.CrossRefPubMed
27.
Gelber RP, Ross GW, Petrovitch H, Masaki KH, Launer LJ, White LR. Antihypertensive medication use and risk of cognitive impairment: The Honolulu-Asia Aging Study. Neurology. 2013;81:888–95.CrossRefPubMedCentralPubMed
28.
Petrovitch H, Galanis DJ, Launer LJ, Harris TB, Foley DJ, White LR. Smoking history in middle age and subsequent cognitive performance in elderly Japanese-American men. The Honolulu-Asia Aging Study. Am J Epidemiol. 1997;145:507–15.CrossRefPubMed
29.
Galanis DJ, Joseph C, Masaki KH, Petrovitch H, Ross GW, White LR. A longitudinal study of drinking and cognitive performance in elderly Japanese American men: The Honolulu-Asia Aging Study. Am J Public Health. 2000;90:1254–9.CrossRefPubMedCentralPubMed
30.
Small B, Dixon R, McArdle J. Tracking cognition-health changes from 55 to 95 years of age. J Gerontol B Psychol Sci Soc Sci. 2011;66:i153–61.CrossRefPubMed
31.
Kivimaki M, Shipley M, Marmot M, Singh Manoux A, Sabia S. Body mass index over the adult life course and cognition in late midlife: The Whitehall II cohort study. Am J Clin Nutr. 2009;89:601–7.CrossRefPubMedCentralPubMed
32.
Cosco T, Stephan BCM, Brayne C. Deathless models of aging and the importance of acknowledging the dying process. Can Med Assoc J. 2013;185:751–2.CrossRef
33.
Diehr P, Patrick D. Trajectories of health for older adults over time: accounting fully for death. Ann Intern Med. 2003;139:416–20.CrossRefPubMed
34.
Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, et al. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology. 2000;54:1265–72.CrossRefPubMed
35.
Roberts R, Knopman D, Przybelski S, Mielke MM, Kantarci K, Preboske GM, et al. Association of type 2 diabetes with brain atrophy and cognitive impairment. Neurology. 2014;82:1132–41.CrossRefPubMedCentralPubMed
36.
Westwood A, Beiser A, DeCarli C, Harris TB, Chen TC, He XM, et al. Insulin-like growth factor-1 and risk of Alzheimer dementia and brain atrophy. Neurology. 2014;82:1613–9.CrossRefPubMed
37.
Ford A, Flicker L, Alfonso H, Hankey GJ, Norman PE, van Bockxmeer FM, et al. Plasma homocysteine and MTHFRC677T polymorphism as risk factors for incident dementia. J Neurol Neurosurg Psychiatry. 2012;83:70–5.CrossRefPubMed
38.
39.
Weston A, Hood L. Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine. J Proteome Res. 2004;3:179–96.CrossRefPubMed
40.
Barabási A. Network medicine - from obesity to the “Diseasome”. N Engl J Med. 2007;357:404–7.CrossRefPubMed
41.
Leischow S, Best A, Trochim W, Clark P, Gallagher R, Marcus S, et al. Systems thinking to improve the public’s health. Am J Prev Med. 2008;35:S196–203.CrossRefPubMedCentralPubMed
42.
Buchman A, Boyle PA, Wilson RS, Tang Y, Bennett DA. Frailty is associated with incident Alzheimer’s disease and cognitive decline in the elderly. Psychosom Med. 2007;69:483–9.CrossRefPubMed
43.
Samper-Ternent R, Al Snih S, Raji MA, Markides KS, Ottenbacher KJ. Relationship between frailty and cognitive decline in older Mexican Americans. J Am Geriatr Soc. 2008;56:1845–52.CrossRefPubMedCentralPubMed
44.
Avila-Funes JA, Amieva H, Barberger-Gateau P, Le Goff M, Raoux N, Ritchie K, et al. Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: The Three-City Study. J Am Geriatr Soc. 2009;57:453–61.CrossRefPubMed
45.
Boyle PA, Buchman AS, Wilson RS, Leurgans SE, Bennett DA. Physical frailty is associated with incident mild cognitive impairment in community-based older persons. J Am Geriatr Soc. 2010;58:248–55.CrossRefPubMedCentralPubMed
46.
Solfrizzi V, Scafato E, Frisardi V, Seripa D, Logroscino G, Maggi S, et al. Frailty syndrome and the risk of vascular dementia: The Italian Longitudinal Study on Aging. Alzhimers Dement. 2013;9:113–22.CrossRef
47.
Buchman AS, Yu L, Wilson RS, Schneider JA, Bennett DA. Association of brain pathology with the progression of frailty in older adults. Neurology. 2013;80:2055–61.CrossRefPubMedCentralPubMed
48.
Shankar A, Hamer M, McMunn A, Steptoe A. Social isolation and loneliness: relationships with cognitive function during 4 years of follow-up in the English Longitudinal Study of Ageing. Psychosom Med. 2013;75:161–70.CrossRefPubMed
49.
Holwerda T, Deeg DJ, Beekman AT, van Tilburg TG, Stek ML, Jonker C, et al. Feelings of loneliness, but not social isolation, predict dementia onset: results from the Amsterdam study of the elderly (AMSTEL). J Neurol Neurosurg Psychiatry. 2014;85:135–42.CrossRefPubMed
50.
Zahodne L, Glymour MM, Sparks C, Bontempo D, Dixon R, Manly J. Education does not slow cognitive decline with aging: 12-year evidence from the Victoria longitudinal study. J Int Neuropsychol Soc. 2011;17:1039–46.CrossRefPubMedCentralPubMed
51.
52.
53.
54.
Fontana L, Kennedy BK, Longo VD, Seals D, Melov S. Medical research: treat ageing. Nature. 2014;511:405–7.CrossRefPubMed
Metadata
Title
Cumulative impact of health deficits, social vulnerabilities, and protective factors on cognitive dynamics in late life: a multistate modeling approach
Authors
Joshua J Armstrong
Arnold Mitnitski
Melissa K Andrew
Lenore J Launer
Lon R White
Kenneth Rockwood
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2015
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-015-0120-7

Other articles of this Issue 1/2015

Alzheimer's Research & Therapy 1/2015 Go to the issue

Research

Modulation of Aβ42 in vivo by γ-secretase modulator in primates and humans

Research

Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease

Research

Improved predictive ability of the Montreal Cognitive Assessment for diagnosing dementia in a community-based study

Review

Lung disease as a determinant of cognitive decline and dementia

Research

Alpha-synucleinopathy and neuropsychological symptoms in a population-based cohort of the elderly

Debate

Is the risk of Alzheimer’s disease and dementia declining?