Research

Research in the Kristine Yaffe Lab focuses on the epidemiology of cognitive aging, particularly on evaluating risk factors and biomarkers for cognitive impairment that may lead to strategies to prevent cognitive decline and optimize cognitive aging. Emphasis is placed on identifying risk factors that are potentially modifiable such as health and lifestyle related mechanisms. The lab also aims to determine and examine biomarkers associated with risk of cognitive impairment and dementia in order to help better identify those at risk as well as to increase our understanding of the mechanisms that may contribute or lead to cognitive decline and impairment.

An overview of selected research from the lab can be found below:


Cardiovascular and Metabolic Risk Factors

The association between cardiovascular and other metabolic risk factors and risk of cognitive impairment is one of the major areas of concentration in the Kristine Yaffe Lab.  Risk factors for cognitive decline that have been identified by the group include associations with diabetes and glycemic control, obesity, vascular disease, kidney function, and the metabolic syndrome.

Selected publications:
  • Zeki Al Hazzouri A, Vittinghoff E, Sidney S, Reis JP, Jacobs DR Jr, Yaffe K. Intima-Media Thickness and Cognitive Function in Stroke-Free Middle-Aged Adults: Findings From the Coronary Artery Risk Development in Young Adults Study. Stroke. 2015; 46(8):2190-6.
  • Mayeda ER, Whitmer RA, Yaffe K. Diabetes and Cognition. Clin Geriatr Med. 2015; 31(1):101-115.
  • Yaffe K, Kurella-Tamura M, Ackerson L, Hoang TD, Anderson AH, Duckworth M, Go AS, Krousel-Wood M, Kusek JW, Lash JP, Ojo A, Robinson N, Sehgal AR, Sondheimer JH, Steigerwalk S, Townsend RR. Higher levels of cystatin C are associated with worse cognitive function in older adults with chronic kidney disease: the Chronic Renal Insufficiency Cohort Cognitive Study. J Am Geriatr Soc. 2014; 62(9):1623-9.
  • Yaffe K, Falvey CM, Hamilton N, Harris TB, Simonsick EM, Strotmeyer ES, Shorr RI, Metti A, Schwartz AV. Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Intern Med. 2013; 22;173(14):1300-6.
  • Barnes D, Alexopolous G, Lopez O, Williamsen J, Yaffe K. Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study. Archives of General Psychiatry. 2006; 63(3):273-279.
  • Whitmer R, Gunderson E, Barrett-Connor E, Quesenberry C, Yaffe K. Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. British Medical Journal. 2005; 330(7504):1360-1364.
  • Yaffe K, Kanaya A, Lindquist, K, Simonsick E, Harris T, Shorr R, Tylavsky F, Newman A. The metabolic syndrome, inflammation and risk of cognitive decline. JAMA. 2004; 292(18):2237-2242.
  • Yaffe K, Blackwell T, Kanaya A, Davidowitz N, Barrett-Connor E, Krueger K. Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology. 2004; 63(4):658-663.
  • Yaffe K, Barrett-Connor E, Lin F, Grady D. Serum lipoprotein levels, statin use and cognitive function in older women. Archives of Neurology. 2002; 59(3):378-384.

Sleep Disturbances

The Kristine Yaffe Lab has played a key role in identifying sleep disturbances as an emerging risk factor for cognitive impairment. Major areas of focus include sleep disordered breathing, sleep quality, and circadian rhythms.

Selected publications:
  • Yaffe K, Nasrallah I, Hoang TD, Lauderdale DS, Knutson KL, Carnethon MR, Launer LJ, Lewis CE, Sidney S. Sleep Duration and White Matter Quality in Middle-Aged Adults. Sleep. 2016; 39(9):1743-7.
  • Leng Y, Blackwell T, Stone KL, Hoang TD, Redline S, Yaffe K. Periodic Limb Movements in Sleep are Associated with Greater Cognitive Decline in Older Men without Dementia. Sleep. 2016; 39(10):1807-1810.
  • Yaffe K, Nettiksimmons J, Yesavage J, Byers A. Sleep Quality and Risk of Dementia Among Older Male Veterans. Am J Geriatr Psychiatry. 2015; 23(6): 651-4.
  • Spira AP, Stone KL, Rebok GW, Punjabi NM, Ancoli-Israel S, Yaffe K. Sleep-disordered breathing and functional decline in older women. Journal of the American Geriatrics Society. 2014; 62(11):2040-6.
  • Yaffe K, Falvey C, Hoang TD. Connections between sleep and cognition in older adults. Lancet Neurology. 2014; 13(10):1017-28.
  • Blackwell T, Yaffe K, Laffan A, Ancoli-Israel S, Redline S, Ensrud KE, Song Y, Stone KL; Osteoporotic Fractures in Men (MrOS) Study Group. Associations of objectively and subjectively measured sleep quality with subsequent cognitive decline in older community-dwelling men: the MrOS sleep study. Sleep. 2014; 37 (4):655-63.
  • Spira AP, Covinsky K, Rebok GW, Stone KL, Redline S, Yaffe K. Objectively measured sleep quality and nursing home placement in older women. Journal of the American Geriatrics Society. 2012; 60 (7):1237-43.
  • Blackwell T, Yaffe K, Ancoli-Israel S, Redline S, Ensrud KE, Stefanick ML, Laffan A, Stone KL; Osteoporotic Fractures in Men Study Group. Associations between sleep architecture and sleep-disordered breathing and cognition in older community-dwelling men: the Osteoporotic Fractures in Men Sleep Study. Journal of the American Geriatrics Society. 2011; 59 (12):2217-25.
  • Yaffe K, Laffan AM, Litwack Harrison S, Redline S, Spira AP, Ensrud KE, Ancoli-Israel S, Stone KL. Sleep disordered breathing, hypoxia, and risk of mild cognitive impairment & dementia in older women. JAMA. 2011; 306(6):613-9.
  • Tranah GJ, Blackwell T, Stone KL, Ancoli-Israel S, Paudel ML, Ensrud KE, Cauley JA, Redline S, Hillier TA, Cummings SR, Yaffe K; SOF Research Group. Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women. Annals of Neurology. 2011; 70 (5):722-32.
  • Spira AP, Blackwell T, Stone KL, Redline S, Cauley JA, Ancoli-Israel S, Yaffe K. Sleep-disordered breathing and cognition in older women. Journal of the American Geriatrics Society.2008; 56(1):45-50.
  • Blackwell T, Yaffe K, Ancoli-Israel S, Schneider JL, Cauley JA, Hillier TA, Fink HA, Stone KL; Study of Osteoporotic Fractures Group. Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures. Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2006; 61 (4):405-10.

Lifestyle

Researchers in the Kristine Yaffe Lab have contributed some of the earliest studies supporting a protective relationship between physical activity and cognitive health. The lab continues to explore this association in addition to investigating the benefits of cognitive activity and cognitive reserve for dementia prevention.

Selected Publications:
  • 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; 52(1):1-9.
  • 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; 73(1):73-9.
  • Koyama A, Houston DK, Simonsick EM, Lee JS, Ayonayon HN, Shahar DR, Rosano C, Satterfield S, Yaffe K. Association between the Mediterranean Diet and cognitive decline in a biracial population. Journal of Gerontology: Medical Sciences. 2015 Mar; 70(3):354-9.
  • Hoang TD, Byers AL, Barnes D, Yaffe K. Alcohol consumption patterns and cognitive impairment in older women. Journal of the American Geriatrics Society. 2014; 22(12): 1663-7.
  • Wang S, Luo X, Barnes D, Sano M, Yaffe K. Physical activity and risk of cognitive impairment among oldest-old women. Journal of the American Geriatrics Society. 2014; 22(11):1149-57.
  • Kaup AR, Simonsick EM, Harris TB, Satterfield S, Metti AL, Ayonayon HN, Rubin SM, Yaffe K. Older Adults With Limited Literacy Are at Increased Risk for Likely Dementia. Journal of Gerontology: Medical Sciences. 2014 Jul; 69(7):900-6.
  • Yaffe K, Weston A, Graff-Radford NR, Satterfield S, Simonsick EM, Younkin SG, Younkin LH, Kuller L, Ayonayon HN, Ding J, Harris TB. Association of plasma beta-amyloid level and cognitive reserve with subsequent cognitive decline. JAMA. 2011; 305(3):261-6.
  • Middleton LE, Barnes DE, Lui L-Y, Yaffe K. Physical activity over the life course and its association with cognitive performance and impairment in old age. Journal of the American Geriatrics Society. 2010; 58(7):1322-1326.
  • Barnes D, Tager I, Satariano W, Yaffe K. The relationship between literacy and cognition in well-educated elders. Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2004; 59(4):M390-395.
  • Barnes D, Yaffe K, Satariano W, Tager I. A longitudinal study of cardiorespiratory fitness and cognitive function in healthy older adults. Journal of the American Geriatrics Society. 2003; 51(4):459-465.
  • Yaffe K, Barnes D, Nevitt M, Lui L, Covinsky K. A prospective study of physical activity and cognitive decline in elderly women: women who walk. Archives of Internal Medicine. 2001; 161(14):1703-1708.

Neuropsychiatric Disorders

Research in the Kristine Yaffe Lab also focuses on the relationship between neuropsychiatric disorders and cognitive outcomes in older adults, including associations with depression, post-traumatic stress disorder (PTSD), and traumatic brain injury (TBI). A particular area of research focuses on neuropsychological risk factors among Veteran populations. The Kristine Yaffe Lab was one of the first groups to provide epidemiological evidence of an association between PTSD and dementia and is now also at the forefront of research on the effects of TBI on cognitive aging.

Selected publications:
  • Kaup AR, Peltz C, Kenney K, Kramer JH, Diaz-Arrastia R, Yaffe K. Neuropsychological Profile of Lifetime Traumatic Brain Injury in Older Veterans. J Int Neuropsychol Soc. 2016 Oct 4:1-9. [Epub ahead of print]
  • 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; 73(5):525-31.
  • Kaup AR, Nettiksimmons J, LeBlanc ES, Yaffe K. Memory Complaints and Risk of Cognitive Impairment Nearly Two Decades Later among Older Women. Neurology. 2015; 85(21):1852-58.
  • Gardner RC, Yaffe K. Epidemiology of mild traumatic brain injury and neurodegenerative disease. Mol Cell Neurosci. 2015; 66(Pt B):75-80.
  • Gardner RC, Burke J, Barnes D, Kaup A, Nettiksimmons J, Goldman S, Tanner C, Yaffe K. Traumatic brain injury in later life increases risk for Parkinson’s disease. Ann Neurol. 2015; 77(6):987-95.
  • Gardner RC, Burke JF, Nettiksimmons J, Kaup A, Barnes DE, Yaffe K. Dementia risk after traumatic brain injury versus nonbrain trauma: the role of age and severity. JAMA Neurology. 2014; 71(12):1490-7.
  • Zeki Al Hazzouri A, Vittinghoff E, Byers A, Covinsky K, Blazer D, Diem S, Ensrud KE, Yaffe K. Long-term cumulative depressive symptom burden and risk of cognitive decline and dementia among very old women.  Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2014; 69(5):595-601.
  • Barnes DE, Kaup AR, Kirby K, Byers AL, Diaz Arrastia R, Yaffe K. Traumatic Brain Injury and Risk of Dementia in Older Veterans. Neurology. 2014 Jul 22; 83(4):312-9.
  • Byers AL, Covinsky KE, Neylan TC, Yaffe K. Chronicity of PTSD and risk of disability in older persons. JAMA Psychiatry. 2014 May; 71(5):540-6.
  • Byers AL, Vittinghoff E, Lui LY, Hoang T, Blazer DG, Covinsky KE, Ensrud KE, Cauley JA, Hillier TA, Fredman L, Yaffe K. Twenty-year depressive trajectories among older women Archives of General Psychiatry. 2012; 69(10):1073-9.
  • Barnes DE, Yaffe K, Byers AL, McCormick M, Schaefer C, Whitmer RA. Midlife vs late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia. Archives of General Psychiatry. 2012; 69(5):493-8.
  • Spira AP, Rebok GW, Stone KL, Kramer JH, Yaffe K. Depressive symptoms in oldest-old women: risk of mild cognitive impairment and dementia. American Journal of Geriatric Psychiatry. 2012; 20(12):1006-15.
  • Yaffe K, Vittinghoff E, Lindquist K, Barnes DE, Covinsky KE, Neylan T, Kluse M, Marmar C. Post-traumatic stress disorder and risk of dementia among U.S. Veterans. Archives of General Psychiatry. 2010; 67(6): 608-13.
  • Byers AL, Covinsky KE, Barnes DE, Yaffe K. Dysthymia and depression increase risk of dementia and mortality among older veterans. American Journal of Geriatric Psychiatry. 2012; 20(8):664.
  • Yaffe K, Edwards ER, Covinsky KE, Lui LY, Eng C. Depressive symptoms and risk of mortality in frail, community-living elderly persons. American Journal of Geriatric Psychiatry. 2003; 11(5):561-7.

Biomarkers

Another focus of the Kristine Yaffe Lab is to investigate potential biomarkers associated with cognitive impairment and dementia. Biomarkers that have been studied include inflammatory markers, beta amyloid, markers of cardiovascular health, measures of oxidative stress, structural brain MRI measures, and genetic markers associated with risk of cognitive decline and dementia.

Selected Publications:
  • 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.
  • Kaup AR, Nettiksimmons J, Harris TB, Sink KM, Satterfield S, Metti AL, Ayonayon HN, Yaffe K. for the Health ABC Study. Cognitive resilience to Apolipoprotein E ε4: Contributing factors in black and white older adults. JAMA Neurology. 2015 Mar; 72(3):340-8.
  • 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.
  • Metti AL, Yaffe K, Boudreau RM, Ganguli M, Lopez OL, Stone KL, Cauley JA.Change in Inflammatory Markers and Cognitive Status in the Oldest-Old Women from the Study of Osteoporotic Fractures. J Am Geriatr Soc. 2014 Apr 2; 62(4): 662-6.
  • Nettiksimmons J, Simonsick EM, Harris T, Satterfield S, Rosano C, Yaffe K; Health ABC Study. The Associations between Serum Brain-Derived Neurotrophic Factor, Potential Confounders, and Cognitive Decline: A Longitudinal Study. PLoS One. 2014 Mar 26; 9(3): e91339.
  • Yokoyama JS, Evans DS, Coppola G, Kramer JH, Tranah GJ, Yaffe K. Genetic modifiers of cognitive maintenance among older adults. Hum Brain Mapp. 2014 Sep; 35(9):4556-65.
  • Koyama A, O'Brien J, Weuve J, Blacker D, Metti AL, Yaffe K. The role of peripheral inflammatory markers in dementia and Alzheimer's disease: a meta-analysis. J Gerontol A Biol Sci Med Sci. 2013 Apr;68(4):433-40.
  • Koyama A, Stone K, Yaffe K.Serum oxidized low-density lipoprotein level and risk of cognitive impairment in older women.Neurobiol Aging. 2013 Feb;34(2):634-635.
  • Yaffe K, Lindquist K, Schwartz AV, Vitartas C, Vittinghoff E, Satterfield S, Simonsick EM, Launer L, Rosano C, Cauley JA, Harris T.Advanced glycation end product level, diabetes, and accelerated cognitive aging.Neurology. 2011 Oct 4;77(14):1351-6.
  • Yaffe K, Weston A, Graff-Radford NR, Satterfield S, Simonsick EM, Younkin SG, Younkin LH, Kuller L, Ayonayon HN, Ding J, Harris TB. Association of plasma beta-amyloid level and cognitive reserve with subsequent cognitive decline.JAMA. 2011 Jan 19;305(3):261-6.