Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-21T07:47:09.216Z Has data issue: false hasContentIssue false
  • English
  • Français

Independent and joint effects of vascular and cardiometabolic risk factor pairs for risk of all-cause dementia: a prospective population-based study

Published online by Cambridge University Press:  28 August 2019

C. Elizabeth Shaaban Open the ORCID record for C. Elizabeth Shaaban [Opens in a new window] ,
Yichen Jia ,
Chung-Chou H. Chang  and
Mary Ganguli Open the ORCID record for Mary Ganguli [Opens in a new window]
C. Elizabeth Shaaban*
Affiliation:
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA
Yichen Jia
Affiliation:
Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
Chung-Chou H. Chang
Affiliation:
Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Mary Ganguli
Affiliation:
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
*
Correspondence should be addressed to: C. Elizabeth Shaaban, Department of Epidemiology, Graduate School of Public Health, 130 DeSoto Street, 5121B Public Health Building, Pittsburgh, PA 15261. Phone: (412)-383-2623; E-mail: [email protected].
Get access

Abstract

Objectives:

To assess independent and joint effects of pairs of vascular and cardiometabolic risk factors (VCMRFs) in relation to risk of all-cause dementia.

Design:

Population-based longitudinal cohort study of cognitive impairment. We used an algorithm to select pairs of VCMRFs and tested their joint effects in time-dependent Cox models. We used attributable proportions (AP) to measure the proportion of risk from interactions beyond any additive effect.

Setting:

Economically depressed small-town population.

Participants:

Adults age 65+ years with up to 10 yearly study visits (N=1701, median (Q1, Q3) age, 78 (71.0, 83.0), 62.3% female, 94.9% white).

Results:

Among 1701 participants free from prevalent dementia with at least one follow-up visit, 109 developed incident all-cause dementia. In pairings of APOE*4 with hypertension (HTN) and congestive heart failure (CHF), the variables contributed independently and additively to all-cause dementia risk. In pairings of APOE*4 with stroke and stroke with CHF, the variables demonstrated independent contributions to all-cause dementia risk; their joint effects showed excess detriment demonstrating synergistic interactions (joint HR [95% CI]: 28.33 [6.74, 119.01] and 50.30 [14.57, 173.57] respectively, fully adjusted models). Physical activity (PA) was independently associated with lower all-cause dementia risk when paired with APOE*4, stroke, and CHF in unadjusted models; these associations did not survive covariate adjustment. The joint effect of low PA and APOE*4 was associated with additively increased all-cause dementia risk (joint HR [95% CI]: 4.61 [2.07, 10.23], fully adjusted model).

Conclusions:

Reduction of VCMRFs, including low PA, could be valuable for dementia prevention, especially among APOE*4 carriers.

Keywords

Alzheimer‘s disease (AD)apolipoprotein E (APOE)cerebral vascular disease (CVD)dementiaepidemiology
Type
Original Research Article
Information
International Psychogeriatrics , Volume 31 , Issue 10: Issue Theme: Dementia and the Society , October 2019 , pp. 1421 - 1432
Copyright
© International Psychogeriatric Association 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adelborg, K., Horvath-Puho, E., Ording, A., Pedersen, L., Toft Sorensen, H. and Henderson, V. W. (2017). Heart failure and risk of dementia: a Danish nationwide population-based cohort study. European Journal of Heart Failure, 19, 253–260.CrossRefGoogle ScholarPubMed
Andersson, T., Alfredsson, L., Kallberg, H., Zdravkovic, S. and Ahlbom, A. (2005). Calculating measures of biological interaction. European Journal of Epidemiology, 20, 575–579.CrossRefGoogle ScholarPubMed
Azarpazhooh, M.R., Avan, A., Cipriano, L.E., Munoz, D.G., Sposato, L.A. and Hachinski, V. (2018). Concomitant vascular and neurodegenerative pathologies double the risk of dementia. Alzheimer’s & Dementia, 14, 148–156.10.1016/j.jalz.2017.07.755CrossRefGoogle Scholar
Baumgart, M., Snyder, H.M., Carrillo, M.C., Fazio, S., Kim, H. and Johns, H. (2015). Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimer’s & Dementia, 11, 718–726.CrossRefGoogle ScholarPubMed
Benjamini, Y. and Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society: Series B (Methodological), 57, 289–300.Google Scholar
Berkowitz, C.L., Mosconi, L., Rahman, A., Scheyer, O., Hristov, H. and Isaacson, R.S. (2018). Clinical Application of APOE in Alzheimer’s Prevention: A Precision Medicine Approach. The Journal of Prevention of Alzheimer’s Disease, 5, 245–252.Google ScholarPubMed
Choi, B.R. et al. (2006). Factors associated with decreased cerebral blood flow in congestive heart failure secondary to idiopathic dilated cardiomyopathy. The American Journal of Cardiology, 97, 1365–1369.CrossRefGoogle ScholarPubMed
de Frias, C.M., Schaie, K.W. and Willis, S.L. (2014). Hypertension moderates the effect of APOE on 21-year cognitive trajectories. Psychology and Aging, 29, 431–439.CrossRefGoogle ScholarPubMed
de Leeuw, F.E., et al. (2004). Interaction between hypertension, apoE, and cerebral white matter lesions. Stroke, 35, 1057–1060.CrossRefGoogle ScholarPubMed
Diniz, B.S., Butters, M.A., Albert, S.M., Dew, M.A. and Reynolds, C.F. (2013). Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. British Journal of Psychiatry, 202, 329–335.CrossRefGoogle ScholarPubMed
Erickson, K.I., Miller, D.L. and Roecklein, K.A. (2012). The aging hippocampus: interactions between exercise, depression, and BDNF. Neuroscientist, 18, 82–97.CrossRefGoogle ScholarPubMed
Erickson, K.I. et al. (2010). Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study. Neurology, 75, 1415–1422.CrossRefGoogle ScholarPubMed
Etnier, J.L. et al. (2007). Cognitive performance in older women relative to ApoE-epsilon4 genotype and aerobic fitness. Medicine & Science in Sports & Exercise, 39, 199–207.CrossRefGoogle ScholarPubMed
Ferguson, T.W., Komenda, P. and Tangri, N. (2015). Cystatin C as a biomarker for estimating glomerular filtration rate. Current Opinion in Nephrology and Hypertension, 24, 295–300.CrossRefGoogle ScholarPubMed
Folstein, M.F., Folstein, S.E. and McHugh, P.R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.10.1016/0022-3956(75)90026-6CrossRefGoogle ScholarPubMed
Ganguli, M., Gilby, J., Seaberg, E. and Belle, S. (1995). Depressive Symptoms and Associated Factors in a Rural Elderly Population: The MoVIES Project. The American Journal of Geriatric Psychiatry, 3, 144–160.CrossRefGoogle Scholar
Huang, Y. (2010). Abeta-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer’s disease. Trends in Molecular Medicine, 16, 287–294.CrossRefGoogle ScholarPubMed
Hughes, T.F., Becker, J.T., Lee, C.W., Chang, C.C. and Ganguli, M. (2015). Independent and combined effects of cognitive and physical activity on incident MCI. Alzheimer’s & Dementia, 11, 1377–1384.CrossRefGoogle ScholarPubMed
Intlekofer, K.A. and Cotman, C.W. (2013). Exercise counteracts declining hippocampal function in aging and Alzheimer’s disease. Neurobiology of Disease, 57, 47–55.CrossRefGoogle ScholarPubMed
Ivan, C.S. et al. (2004). Dementia after stroke: the Framingham Study. Stroke, 35, 1264–1268.CrossRefGoogle ScholarPubMed
Jin, Y.P., Di Legge, S., Ostbye, T., Feightner, J.W. and Hachinski, V. (2006). The reciprocal risks of stroke and cognitive impairment in an elderly population. Alzheimer’s & Dementia, 2, 171–178.CrossRefGoogle Scholar
Jin, Y.P., Ostbye, T., Feightner, J.W., Di Legge, S. and Hachinski, V. (2008). Joint effect of stroke and APOE 4 on dementia risk: the Canadian Study of Health and Aging. Neurology, 70, 9–16.CrossRefGoogle ScholarPubMed
Jorgensen, D.R., Shaaban, C.E., Wiley, C.A., Gianaros, P.J., Mettenburg, J. and Rosano, C. (2018). A population neuroscience approach to the study of cerebral small vessel disease in mid- and late-life: an Invited Review. American Journal of Physiology-Heart and Circulatory Physiology.CrossRefGoogle Scholar
Kivipelto, M. et al. (2008). Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population-based study. Journal of Cellular and Molecular Medicine, 12, 2762–2771.CrossRefGoogle ScholarPubMed
Klein, J.P. and Moeschberger, M.L. (2003). Survival Analysis: Techniques for Censored and Truncated Data. New York: Springer.Google Scholar
Kloppenborg, R.P., Nederkoorn, P.J., Geerlings, M.I. and van den Berg, E. (2014). Presence and progression of white matter hyperintensities and cognition: a meta-analysis. Neurology, 82, 2127–2138.CrossRefGoogle ScholarPubMed
Kokmen, E., Whisnant, J.P., O’Fallon, W.M., Chu, C.P. and Beard, C.M. (1996). Dementia after ischemic stroke: a population-based study in Rochester, Minnesota (1960-1984). Neurology, 46, 154–159.CrossRefGoogle Scholar
Larson, E.B. (2019). Risk factors for cognitive decline and dementia. UpToDate. Available at: https://www.uptodate.com/contents/risk-factors-for-cognitive-decline-and-dementia.Google Scholar
Llewellyn, D.J. et al. (2010). Vascular health, diabetes, APOE and dementia: the Aging, Demographics, and Memory Study. Alzheimer’s Research & Therapy, 2, 19.CrossRefGoogle ScholarPubMed
Morris, J.C. (1993). The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology, 43, 2412–2414.CrossRefGoogle ScholarPubMed
Pantoni, L., Fierini, F. and Poggesi, A. (2015). Impact of cerebral white matter changes on functionality in older adults: an overview of the LADIS Study results and future directions. Geriatrics & Gerontology International, 15 Suppl 1, 10–16.CrossRefGoogle ScholarPubMed
Peila, R. et al. (2001). Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment: the Honolulu-Asia aging study. Stroke, 32, 2882–2889.CrossRefGoogle ScholarPubMed
Perales, J., Hinton, L., Burns, J. and Vidoni, E.D. (2018). Cardiovascular health and cognitive function among Mexican older adults: cross-sectional results from the WHO Study on Global Ageing and Adult Health. International Psychogeriatrics, 30, 1827–1836.CrossRefGoogle Scholar
Piercy, K.L. et al. (2018). The Physical Activity Guidelines for Americans. JAMA, 320, 2020–2028.CrossRefGoogle ScholarPubMed
Prins, N.D. et al. (2004). Cerebral white matter lesions and the risk of dementia. Archives of Neurology, 61, 1531–1534.CrossRefGoogle Scholar
Qiu, C., Winblad, B., Marengoni, A., Klarin, I., Fastbom, J. and Fratiglioni, L. (2006). Heart failure and risk of dementia and Alzheimer disease: a population-based cohort study. Archives of Internal Medicine, 166, 1003–1008.CrossRefGoogle ScholarPubMed
R Core Team. (2018). R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing.Google Scholar
Reitz, C., Bos, M.J., Hofman, A., Koudstaal, P.J. and Breteler, M.M. (2008). Prestroke cognitive performance, incident stroke, and risk of dementia: the Rotterdam Study. Stroke, 39, 36–41.CrossRefGoogle ScholarPubMed
Rosano, C. et al. (2017). Hippocampal response to a 24-month physical activity intervention in sedentary older adults. The American Journal of Geriatric Psychiatry, 25, 209–217.CrossRefGoogle ScholarPubMed
Roy, B., Woo, M.A., Wang, D.J.J., Fonarow, G.C., Harper, R.M. and Kumar, R. (2017). Reduced regional cerebral blood flow in patients with heart failure. European Journal of Heart Failure, 19, 1294–1302.CrossRefGoogle ScholarPubMed
Rusanen, M. et al. (2014). Heart diseases and long-term risk of dementia and Alzheimer’s disease: a population-based CAIDE study. Journal of Alzheimer’s Disease, 42, 183–191.CrossRefGoogle ScholarPubMed
Salive, M.E. (2013). Multimorbidity in older adults. Epidemiologic Reviews, 35, 75–83.CrossRefGoogle ScholarPubMed
SAS Inst. (2013). The SAS system for Windows. Cary, NC: SAS Institute.Google Scholar
Snyder, H.M. et al. (2015). Vascular contributions to cognitive impairment and dementia including Alzheimer’s disease. Alzheimer’s & Dementia, 11, 710–717.CrossRefGoogle ScholarPubMed
Therneau, T.M. (2015). A Package for Survival Analysis in S. Version 2.38. Available at: https://CRAN.R-project.org/package=survival.Google Scholar
van Dijk, E.J. et al. (2005). C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation, 112, 900–905.CrossRefGoogle ScholarPubMed
Vemuri, P. et al. (2017). Age, vascular health, and Alzheimer disease biomarkers in an elderly sample. Annals of Neurology, 82, 706–718.CrossRefGoogle Scholar
Vermeer, S.E. et al. (2002). Homocysteine, silent brain infarcts, and white matter lesions: the Rotterdam Scan Study. Annals of Neurology, 51, 285–289.CrossRefGoogle ScholarPubMed
Wagner, M., Helmer, C., Tzourio, C., Berr, C., Proust-Lima, C. and Samieri, C. (2018). Evaluation of the concurrent trajectories of cardiometabolic risk factors in the 14 years before dementia. JAMA Psychiatry, 75, 1033–1042.CrossRefGoogle ScholarPubMed
Walker, K.A., Power, M.C. and Gottesman, R.F. (2017). Defining the relationship between hypertension, cognitive decline, and dementia: a review. Current Hypertension Reports, 19, 24.CrossRefGoogle ScholarPubMed
Walldius, G. and Jungner, I. (2006). The apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy--a review of the evidence. Journal of Internal Medicine, 259, 493–519.CrossRefGoogle Scholar
Wong, A., Mok, V., Fan, Y.H., Lam, W.W., Liang, K.S. and Wong, K.S. (2006). Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease. Journal of Neurology, 253, 441–447.CrossRefGoogle ScholarPubMed
Yuan, M. et al. (2018). Associations between modifiable lifestyle factors and multidimensional cognitive health among community-dwelling old adults: stratified by educational level. International Psychogeriatrics, 30, 1465–1476.CrossRefGoogle ScholarPubMed
Zhu, L. et al. (2000). Incidence of dementia in relation to stroke and the apolipoprotein E epsilon4 allele in the very old. Findings from a population-based longitudinal study. Stroke, 31, 53–60.CrossRefGoogle ScholarPubMed
Supplementary material: Image

Shaaban et al. supplementary material

Shaaban et al. supplementary material 1

Download Shaaban et al. supplementary material(Image)
Image 66.3 KB
Supplementary material: File

Shaaban et al. supplementary material

Shaaban et al. supplementary material 2

Download Shaaban et al. supplementary material(File)
File 17.9 KB
Supplementary material: Image

Shaaban et al. supplementary material

Shaaban et al. supplementary material 3

Download Shaaban et al. supplementary material(Image)
Image 135 KB