Skip to main content Accessibility help
×
Home

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

  • C. Elizabeth Shaaban (a1) (a2), Yichen Jia (a3), Chung-Chou H. Chang (a3) (a4) and Mary Ganguli (a1) (a5) (a6)

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.

Copyright

Corresponding author

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: Beth.Shaaban@pitt.edu.

References

Hide All
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, 253260.
Andersson, T., Alfredsson, L., Kallberg, H., Zdravkovic, S. and Ahlbom, A. (2005). Calculating measures of biological interaction. European Journal of Epidemiology, 20, 575579.
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, 148156.10.1016/j.jalz.2017.07.755
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, 718726.
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, 289300.
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, 245252.
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, 13651369.
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, 431439.
de Leeuw, F.E., et al. (2004). Interaction between hypertension, apoE, and cerebral white matter lesions. Stroke, 35, 10571060.
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, 329335.
Erickson, K.I., Miller, D.L. and Roecklein, K.A. (2012). The aging hippocampus: interactions between exercise, depression, and BDNF. Neuroscientist, 18, 8297.
Erickson, K.I. et al. (2010). Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study. Neurology, 75, 14151422.
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, 199207.
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, 295300.
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, 189198.10.1016/0022-3956(75)90026-6
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, 144160.
Huang, Y. (2010). Abeta-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer’s disease. Trends in Molecular Medicine, 16, 287294.
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, 13771384.
Intlekofer, K.A. and Cotman, C.W. (2013). Exercise counteracts declining hippocampal function in aging and Alzheimer’s disease. Neurobiology of Disease, 57, 4755.
Ivan, C.S. et al. (2004). Dementia after stroke: the Framingham Study. Stroke, 35, 12641268.
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, 171178.
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, 916.
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.
Kivipelto, M. et al. (2008). Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population-based study. Journal of Cellular and Molecular Medicine, 12, 27622771.
Klein, J.P. and Moeschberger, M.L. (2003). Survival Analysis: Techniques for Censored and Truncated Data. New York: Springer.
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, 21272138.
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, 154159.
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.
Llewellyn, D.J. et al. (2010). Vascular health, diabetes, APOE and dementia: the Aging, Demographics, and Memory Study. Alzheimer’s Research & Therapy, 2, 19.
Morris, J.C. (1993). The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology, 43, 24122414.
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, 1016.
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, 28822889.
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, 18271836.
Piercy, K.L. et al. (2018). The Physical Activity Guidelines for Americans. JAMA, 320, 20202028.
Prins, N.D. et al. (2004). Cerebral white matter lesions and the risk of dementia. Archives of Neurology, 61, 15311534.
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, 10031008.
R Core Team. (2018). R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing.
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, 3641.
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, 209217.
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, 12941302.
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, 183191.
Salive, M.E. (2013). Multimorbidity in older adults. Epidemiologic Reviews, 35, 7583.
SAS Inst. (2013). The SAS system for Windows. Cary, NC: SAS Institute.
Snyder, H.M. et al. (2015). Vascular contributions to cognitive impairment and dementia including Alzheimer’s disease. Alzheimer’s & Dementia, 11, 710717.
Therneau, T.M. (2015). A Package for Survival Analysis in S. Version 2.38. Available at: https://CRAN.R-project.org/package=survival.
van Dijk, E.J. et al. (2005). C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation, 112, 900905.
Vemuri, P. et al. (2017). Age, vascular health, and Alzheimer disease biomarkers in an elderly sample. Annals of Neurology, 82, 706718.
Vermeer, S.E. et al. (2002). Homocysteine, silent brain infarcts, and white matter lesions: the Rotterdam Scan Study. Annals of Neurology, 51, 285289.
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, 10331042.
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.
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, 493519.
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, 441447.
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, 14651476.
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, 5360.

Keywords

Type Description Title
UNKNOWN
Supplementary materials

Shaaban et al. supplementary material
Shaaban et al. supplementary material 1

 Unknown (66 KB)
66 KB
WORD
Supplementary materials

Shaaban et al. supplementary material
Shaaban et al. supplementary material 2

 Word (18 KB)
18 KB
UNKNOWN
Supplementary materials

Shaaban et al. supplementary material
Shaaban et al. supplementary material 3

 Unknown (135 KB)
135 KB

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

  • C. Elizabeth Shaaban (a1) (a2), Yichen Jia (a3), Chung-Chou H. Chang (a3) (a4) and Mary Ganguli (a1) (a5) (a6)

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed