Women and Brain Aging Disclosures Consultant: Pfizer, Noven - PDF document

9/23/2015 Women and Brain Aging Disclosures • Consultant: Pfizer, Noven Pauline M. Maki, PhD • Speaking Honorarium: Abbott Professor of Psychiatry and Psychology, UIC President, North American Menopause Society • Research: NIH Objectives Objectives 1. Describe sex/gender differences in 1. Describe sex/gender differences in Alzheimer’s Disease Alzheimer’s Disease (AD) 2.Understand how reproductive aging and 2. Describe sex/gender differences in risk hormone therapy might influence the risk factors for AD for AD 3. Elucidate the role of reproductive aging on 3.Describe sex differences in risk factors for cognition and brain aging in women AD. Alois Alzheimer 1

9/23/2015 Prevalence of Alzheimer's Disease (AD) Women and AD • More women than men have AD • At age 65, women without Alzheimer’s have more than a 1 in 6 chance of • Of 5 million with AD in US developing AD during the remainder of • 3.2 million are women their lives, compared with a 1 in 11 chance for men. • 1.8 million are men • Women in their 60s are about twice as • ~2/3rds of AD patients in US are likely to develop AD over the rest of their women lives as they are to develop breast cancer. Andersen K, Launer LJ, Dewey ME, et al. Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group. Neurology. Dec 10 1999;53(9):1992-1997. Source: Heron, M. CDC National Vital Statistics Report; Vol 62, No 6, 2013 Source: Heron, M. CDC National Vital Statistics Report; Vol 62, No 6, 2013 Why is the Prevalence of AD Higher in Greater cognitive deterioration in women than men with Alzheimer's: A meta analysis Women Than Men? Male Advantage Female Advantage Cognitive Domain • Major contributing factor to higher Semantic prevalence of AD in women is that women Nonsemantic live longer than men Verbal • Age is the major risk factor for AD Visuospatial Memory -1.0 -0.75 -0.50 -0.25 0 0.25 0.50 0.75 Effect Size (95% CI) Heron, M. CDC National Vital Statistics Report; Vol 62, No 6, 2013; Andersen K, Launer LJ, Dewey ME, et al. Gender Heron, M. CDC National Vital Statistics Report; Vol 62, No 6, 2013; Andersen K, Launer LJ, Dewey ME, et al. Gender Adapted from Irvine, et al. Greater cognitive deterioration in women than men with Alzheimer's disease: A meta differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group. differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group. analysis JCEN . 2012; 34 (9) 989-998. Neurology. Dec 10 1999;53(9):1992-1997. Neurology. Dec 10 1999;53(9):1992-1997. . . 2

9/23/2015 Cost of AD from 2010-2050 will exceed Prevalence of AD Will Triple By 2050 $20 trillion Age 65-74 Age 75-84 Age 85+ Total Cumulative Medicare 14 costs will amount to 12 Number of People with AD Number of People with AD $11.4 trillion, and 10 (in millions) (in millions) cumulative Medicaid to 8 $3.6 trillion over the 6 same period. 4 2 0 2000 2010 2020 2030 2040 2050 Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Archives of Neurology. 2003;60(8):1119-1122. the 2000 census. Archives of Neurology. 2003;60(8):1119-1122. Lewin Group for the Alzheimer’s Association: www.alz.org/trajectory Lewin Group for the Alzheimer’s Association: www.alz.org/trajectory AD Can Be Prevented/Delayed Objectives 1. Describe sex/gender differences in Alzheimer’s Disease (AD) 2. Describe sex/gender differences in risk factors for AD 3. Elucidate the role of reproductive aging on cognition and brain aging in women Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol . 2011;10:819-828 3

9/23/2015 Prevalence of Risk Factors for AD: Differences Body Mass Index (BMI) > 30 doubles risk of AD 21 Body Mass Index (BMI) > 30 doubles risk of AD 21 Between Men and Women years later years later Compared to men, women have: • Higher BMI • Lower rates of exercise • Higher cholesterol levels • Higher rates of hypertension in older adulthood • Higher rates of depression • Higher rates of television viewing in adulthood • Greater risk due to the predominant genetic risk factor (ApoE4) Kivipelto M, Ngandu T, Fratiglioni L, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol. Oct 2005;62(10):1556-1560. Harris CV, Bradlyn AS, Coffman J, Gunel E, Cottrell L. BMI-based body size guides for women and men: development and validation of a novel pictorial method to assess weight- related concepts. Int J Obes (Lond). Feb 2008;32(2):336-342. Anstey KJ, Cherbuin N, Budge M, Young J. Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev. May 2011;12(5):e426-437. APOE4 Status Matters More in Healthy Female Advantage in Verbal Memory Older Women Than in Men • Women show a lifelong advantage in verbal memory A single APOE4 allele increases • Thought to be largely due to the risk of clinical organizational effects of sex steroid decline in healthy hormones on brain systems underlying older women, but memory not men. Kramer J, Delis D, Daniel M. Sex differences in verbal learning. Journal of Clinical Psychology. 1988;44:907-915. Altmann et al. Sex modifies the APOE-related risk of developing Alzheimer diseases. Annals Kramer J, Yaffe K, Lengenfelder J, Delis D. Age and gender interactions on verbal memory performance. Journal of the International of Neurology. 2014; 75(4):563-73. Neuropsychological Society. 2003;9(1):97-102. 4

9/23/2015 Women Show an Advantage In Verbal Importance of Verbal Memory Memory Despite Similar Levels of Hippocampal Atrophy • Declines in verbal memory are the Delayed Recall earliest signs of Alzheimer’s disease Immediate Recall Women perform better (AD) and central to its diagnosis RAVLT Total Words Recalled ─ F than men ─ F Females: β =, p= ─ M Females: β =, p= ─ M • New findings suggest that women maintain verbal memory early in the course of AD and then rapidly decline P = .001 Once atrophy reaches a threshold, P = .001 Males: β =, p= Males: β =, p= women rapidly decline Hippocampal Volume Hippocampal Volume Tierney MC, Yao C, Kiss A, McDowell I. Neuropsychological tests accurately predict incident Alzheimer disease after 5 and 10 years. Neurology. Jun 14 2005;64(11):1853-1859. Linn RT, Wolf PA, Bachman DL, et al. The 'preclinical phase' of probable Alzheimer's disease. A 13-year prospective study of the Framingham cohort. Arch Neurol. May 1995;52(5):485-490. Memory Performance Depends on Menopausal Status: Worsens during Transition Objectives Penn Ovarian Aging Study 1. Describe sex/gender differences in Alzheimer’s Disease (AD) 2. Describe sex/gender differences in risk factors for AD 3. Elucidate the role of reproductive aging on cognition and brain aging in women n = 403 followed for 14 years Epperson CN, Sammel MD, Freeman EW. Menopause effects on verbal memory: findings from a longitudinal community cohort. J Clin Endocrinol Metab. Sep 2013;98(9):3829-3838. 5

9/23/2015 Memory and Other Cognitive Functions Relationship between Cognitive Changes and Vary with Menopausal Stage Menopausal Symptoms Megamonalisa.com n = 117 Weber, M., Rubin, L.H., Maki, P.M. Cognition in the perimenopause: The effect of transition stage. Menopause. 2013;20(5):511-517 Measuring Physiologic VMS Objectively Women under-report VMS with Ambulatory Monitors • Biolog Skin Conductance Monitor • Objective hot flash defined as a 2 mmho increase in skin conductance across a 30 second period • Button press used for subjective recognition of hot flash Maki PM, Drogos LL, Rubin LH, et al. Objective hot flashes are negatively related to verbal memory performance in midlife women. Menopause. 2008;15(5):848-856. 6