Our group focuses on the epidemiology of cognitive aging. Emphasis is placed on evaluating risk factors that are potentially modifiable, such as health and lifestyle-related mechanisms.
Risk and Resilience Factors for Cognitive Aging
Our team has been at the forefront of identifying modifiable risk and resilience factors for cognitive and brain health. Team members have led some of the earliest investigations on the role of cardiovascular and metabolic risk factors, lifestyle behaviors, sleep disturbances, and other psychiatric and medical comorbidities.
Selected Publications
- Cavaillès, C., Yaffe, K., Blackwell, T., Buysse, D., Stone, K., & Leng, Y. (2023). Multidimensional Sleep Health and Long-Term Cognitive Decline in Community-Dwelling Older Men. Journal of Alzheimer's disease : JAD, 96(1), 65–71.
- Brenowitz WD, Robbins NM, Strotmeyer ES, Yaffe K. Associations of Lower Extremity Peripheral Nerve Impairment and Risk of Dementia in Black and White Older Adults. Neurology. 2022 May 3;98(18):e1837-e1845.
- Whitaker KM, Zhang D, Pettee Gabriel K, Ahrens M, Sternfeld B, Sidney S, Jacobs DR Jr, Palta P, Yaffe K. Longitudinal Associations of Midlife Accelerometer Determined Sedentary Behavior and Physical Activity With Cognitive Function: The CARDIA Study. J Am Heart Assoc. 2021 Feb 2;10(3):e018350.
- Leng Y, Ackley SF, Glymour MM, Yaffe K, Brenowitz WD. Genetic Risk of Alzheimer's Disease and Sleep Duration in Non-Demented Elders. Ann Neurol. 2021 Jan;89(1):177-181.
- Rouch L, Vidal JS, Hoang T, Cestac P, Hanon O, Yaffe K. Systolic blood pressure postural changes variability is associated with greater dementia risk. Neurology. 2020 Oct 6;95(14):e1932-e1940.
- McEvoy CT, Hoang T, Sidney S, Steffen LM, Jacobs DR Jr, Shikany JM, Wilkins JT, Yaffe K. Dietary patterns during adulthood and cognitive performance in midlife: The CARDIA study. Neurology. 2019 Apr 2;92(14):e1589-e1599.
- Kaup AR, Byers AL, Falvey C, Simonsick EM, Satterfield S, Ayonayon HN, Smagula SF, Rubin SM, Yaffe K. Trajectories of Depressive Symptoms in Older Adults and Risk of Dementia. JAMA Psychiatry. 2016 May 1;73(5):525-31.
Military Risk Factors
Our group is committed to understanding the unique constellation of military risk factors for dementia in the veteran population. We are especially interested in exploring how factors like TBI and PTSD affect the cognitive health of Veteran and civilian populations in addition to examining the interaction between military risk factors, comorbidities, and cognitive outcomes.
Selected Publications
- Schneider ALC, Peltz CB, Li Y, Bahorik A, Gardner RC, Yaffe K. Traumatic Brain Injury and Long-Term Risk of Stroke Among US Military Veterans. Stroke. 2023 Jun 19. doi: 10.1161/STROKEAHA.123.042360.
- Gardner RC, Bahorik A, Kornblith ES, Allen IE, Plassman BL, Yaffe K. Systematic Review, Meta-Analysis, and Population Attributable Risk of Dementia Associated with Traumatic Brain Injury in Civilians and Veterans. J Neurotrauma. 2023 Apr;40(7-8):620-634.
- Martinez S, Yaffe K, Li Y, Byers AL, Peltz CB, Barnes DE. Agent Orange Exposure and Dementia Diagnosis in US Veterans of the Vietnam Era. JAMA Neurol. 2021 Apr 1;78(4):473-477.
- Bahorik A, Bobrow K, Hoang T, Yaffe K. Increased risk of dementia in older female US veterans with alcohol use disorder. Addiction. 2021 Jan 15.
- Kornblith E, Peltz CB, Xia F, Plassman B, Novakovic-Apopain T, Yaffe K. Sex, race, and risk of dementia diagnosis after traumatic brain injury among older veterans. Neurology. 2020 Sep 29;95(13):e1768-e1775.
- Yaffe K, Lwi SJ, Hoang TD, Xia F, Barnes DE, Maguen S, Peltz CB. Military-related risk factors in female veterans and risk of dementia. Neurology. 2019 Jan 15;92(3):e205-e211.
- Barnes DE, Byers AL, Gardner RC, Seal KH, Boscardin WJ, Yaffe K. Association of Mild Traumatic Brain Injury With and Without Loss of Consciousness With Dementia in US Military Veterans. JAMA Neurol. 2018 Sep 1;75(9):1055-1061.
Life Course Approach to Dementia
Brain changes related to cognitive aging and dementia occur over several decades. Using innovative population-based approaches, our group is investigating risk and resilience factors for brain health across the life course in order to better inform treatment and prevention strategies.
Selected Publications
- Bahorik AL, Hoang TD, Jacobs DR, Levine DA, Yaffe K. Association of Changes in C-Reactive Protein Level Trajectories Through Early Adulthood With Cognitive Function at Midlife: The CARDIA Study. Neurology. 2024 Jul 23;103(2):e209526. doi: 10.1212/WNL.0000000000209526. Epub 2024 Jul 3. PMID: 38959452; PMCID: PMC11226328.
- Jiang, X., Lewis, C. E., Allen, N. B., Sidney, S., & Yaffe, K. (2023). Premature Cardiovascular Disease and Brain Health in Midlife: The CARDIA Study. Neurology, 100(14), e1454–e1463. https://doi.org/10.1212/WNL.0000000000206825
- Brenowitz WD, Fornage M, Launer LJ, Habes M, Davatzikos C, Yaffe K. Alzheimer's Disease Genetic Risk, Cognition, and Brain Aging in Midlife. Ann Neurol. 2023 Mar;93(3):629-634.
- Dintica CS, Habes M, Erus G, Vittinghoff E, Davatzikos C, Nasrallah IM, Launer LJ, Sidney S, Yaffe K. Elevated blood pressure is associated with advanced brain aging in mid-life: A 30-year follow-up of The CARDIA Study. Alzheimers Dement. 2022 Jul 2:10.1002/alz.12725.
- Yaffe K, Vittinghoff E, Hoang T, Matthews K, Golden SH, Zeki Al Hazzouri A. Cardiovascular Risk Factors Across the Life Course and Cognitive Decline: A Pooled Cohort Study. Neurology. 2021 Apr 27;96(17):e2212-e2219.
- Bahorik AL, Sidney S, Kramer-Feldman J, Jacobs DR Jr, Mathew AR, Reis JP, Yaffe K. Early to Midlife Smoking Trajectories and Cognitive Function in Middle-Aged US Adults: the CARDIA Study. J Gen Intern Med. 2021 Jan 26. doi: 10.1007/s11606-020-06450-5.
- Zeki Al Hazzouri A, Vittinghoff E, Zhang Y, Pletcher MJ, Moran AE, Bibbins-Domingo K, Golden SH, Yaffe K. Use of a pooled cohort to impute cardiovascular disease risk factors across the adult life course. Int J Epidemiol. 2019 Jun 1;48(3):1004-1013.
- Hoang TD, Reis J, Zhu N, Jacobs DR Jr, Launer LJ, Whitmer RA, Sidney S, Yaffe K. Effect of Early Adult Patterns of Physical Activity and Television Viewing on Midlife Cognitive Function. JAMA Psychiatry. 2016 Jan;73(1):73-9.
- Yaffe K, Vittinghoff E, Pletcher MJ, Hoang TD, Launer LJ, Whitmer R, Coker LH, Sidney S. Early adult to midlife cardiovascular risk factors and cognitive function. Circulation. 2014 Apr 15;129(15):1560-7.
Multidomain Interventions
The group’s work on risk and resilience factors has been foundational in shaping the current dementia prevention framework, particularly multidomain strategies. In collaboration with Kaiser Seattle, we are piloting the first multidomain dementia intervention in the United States.
Selected Publications
- Yaffe K, Vittinghoff E, Dublin S, et al. Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults: The SMARRT Randomized Clinical Trial. JAMA Intern Med. 2024;184(1):54–62. doi:10.1001/jamainternmed.2023.6279
- Brenowitz WD, Yaffe K. Observational studies in Alzheimer disease: bridging preclinical studies and clinical trials. Nat Rev Neurol. 2022 Dec;18(12):747-757.
- Anstey KJ, Peters R, Zheng L, Barnes DE, Brayne C, Brodaty H, Chalmers J, Clare L, Dixon RA, Dodge H, Lautenschlager NT, Middleton LE, Qiu C, Rees G, Shahar S, Yaffe K. Future Directions for Dementia Risk Reduction and Prevention Research: An International Research Network on Dementia Prevention Consensus. J Alzheimers Dis. 2020;78(1):3-12.
- Marcum ZA, Rosenberg D, Barnes DE, Yaffe K, Larson EB. Engaging Patients to Design the Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT) Intervention: Findings from a Web-Based Survey. J Alzheimers Dis Rep. 2020 Jul 23;4(1):255-260.
- Yaffe K, Barnes DE, Rosenberg D, Dublin S, Kaup AR, Ludman EJ, Vittinghoff E, Peltz CB, Renz AD, Adams KJ, Larson EB. Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): Study Protocol. J Alzheimers Dis. 2019;70(s1):S207-S220.
- Committee on the Public Health Dimensions of Cognitive Aging; Board on Health Sciences Policy; Institute of Medicine. Cognitive Aging: Progress in Understanding and Opportunities for Action. Blazer DG, Yaffe K, Liverman CT, editors. Washington (DC): National Academies Press (US); 2015 Jul 21.
- Barnes DE, Santos-Modesitt W, Poelke G, Kramer AF, Castro C, Middleton LE, Yaffe K. The Mental Activity and eXercise (MAX) trial: a randomized controlled trial to enhance cognitive function in older adults. JAMA Intern Med. 2013 May 13;173(9):797-804.
- Yaffe K, Krueger K, Sarkar S, Grady D, Barrett-Connor E, Cox DA, Nickelsen T; Multiple Outcomes of Raloxifene Evaluation Investigators. Cognitive function in postmenopausal women treated with raloxifene. N Engl J Med. 2001 Apr 19;344(16):1207-13.
Health Disparities
There are significant disparities in risk of dementia and cognitive decline by race, ethnicity, sex, and socioeconomic status. Our team is seeking to understand the impact of these factors and to determine population-based strategies to reduce these disparities.
Selected Publications
- Dintica CS, Bahorik A, Xia F, Kind A, Yaffe K. Dementia Risk and Disadvantaged Neighborhoods. JAMA Neurol. 2023 Jul 19.
- Kornblith E, Peltz CB, Xia F, Plassman B, Novakovic-Apopain T, Yaffe K. Sex, race, and risk of dementia diagnosis after traumatic brain injury among older veterans. Neurology. 2020 Sep 29;95(13):e1768-e1775.
- Caunca MR, Odden MC, Glymour MM, Elfassy T, Kershaw KN, Sidney S, Yaffe K, Launer L, Zeki Al Hazzouri A. Association of Racial Residential Segregation Throughout Young Adulthood and Cognitive Performance in Middle-aged Participants in the CARDIA Study. JAMA Neurol. 2020 Aug 1;77(8):1000-1007
- Lwi SJ, Barnes DE, Xia F, Peltz C, Hoang T, Yaffe K. Ten-Year Prevalence of Cognitive Impairment Diagnoses and Associated Medical and Psychiatric Conditions in a National Cohort of Older Female Veterans. Am J Geriatr Psychiatry. 2019 Apr;27(4):417-425.
- Zeki Al Hazzouri A, Elfassy T, Sidney S, Jacobs D, Pérez Stable EJ, Yaffe K. Sustained Economic Hardship and Cognitive Function: The Coronary Artery Risk Development in Young Adults Study. Am J Prev Med. 2017 Jan;52(1):1-9.
- Kaup AR, Nettiksimmons J, Harris TB, Sink KM, Satterfield S, Metti AL, Ayonayon HN, Yaffe K; Health, Aging, and Body Composition (Health ABC) Study. Cognitive resilience to apolipoprotein E ε4: contributing factors in black and white older adults. JAMA Neurol. 2015 Mar;72(3):340-8.
- Yaffe K, Falvey C, Harris TB, Newman A, Satterfield S, Koster A, Ayonayon H, Simonsick E; Health ABC Study. Effect of socioeconomic disparities on incidence of dementia among biracial older adults: prospective study. BMJ. 2013 Dec 19;347:f7051.
Biomarkers of Cognitive Decline and Dementia
We are also interested in exploring potential biomarkers for cognitive aging and dementia. This work includes publications on inflammatory markers, beta amyloid, markers of cardiovascular health, measures of oxidative stress, structural brain MRI measures, and genetic markers.
Selected Publications
- Jiang X, Bahorik AL, Graff-Radford NR, Yaffe K. Association of Plasma Amyloid-β and Dementia Among Black and White Older Adults. J Alzheimers Dis. 2024;99(2):787-797.
- Jiang X, O'Bryant SE, Johnson LA, Rissman RA, Yaffe K; Health and Aging Brain Study (HABS‐HD) Study Team. Association of cardiovascular risk factors and blood biomarkers with cognition: The HABS-HD study. Alzheimers Dement (Amst). 2023 Mar 8;15(1):e12394.
- O'Bryant SE, Johnson LA, Barber RC, Braskie MN, Christian B, Hall JR, Hazra N, King K, Kothapalli D, Large S, Mason D, Matsiyevskiy E, McColl R, Nandy R, Palmer R, Petersen M, Philips N, Rissman RA, Shi Y, Toga AW, Vintimilla R, Vig R, Zhang F, Yaffe K; HABLE Study Team. The Health & Aging Brain among Latino Elders (HABLE) study methods and participant characteristics. Alzheimers Dement (Amst). 2021 Jun 21;13(1):e12202.
- O'Donovan A, Bahorik A, Sidney S, Launer LJ, Yaffe K. Relationships of inflammation trajectories with white matter volume and integrity in midlife. Brain Behav Immun. 2021 Jan;91:81-88.
- Peltz CB, Kenney K, Gill J, Diaz-Arrastia R, Gardner RC, Yaffe K. Blood biomarkers of traumatic brain injury and cognitive impairment in older veterans. Neurology. 2020 Sep 1;95(9):e1126-e1133.
- Duarte S, Hoang T, Ewing SK, Cawthon PM, Cummings S, Stone KL, Cauley JA, Bauer DC, Hillier TA, Yaffe K. Glycated Peptide Levels Are Associated With Cognitive Decline Among Nondiabetic Older Women. J Gerontol A Biol Sci Med Sci. 2019 Feb 15;74(3):396-399.
- Nettiksimmons J, Tranah G, Evans DS, Yokoyama JS, Yaffe K. Gene-based aggregate SNP associations between candidate AD genes and cognitive decline. Age (Dordr). 2016; 38(2):41.
- Nettiksimmons J, Ayonayon H, Harris T, Phillips CL, Rosano C, Satterfield S, Yaffe K. Development and validation of risk index for cognitive decline using blood-derived markers. Neurology. 2015; 84(7):696-702.