The mission of the Weill Cornell Women’s Brain Initiative (WBI) is to discover sex-based molecular targets and precision therapies to prevent, delay, and minimize risk of Alzheimer’s disease.
The Weill Cornell WBI represents a major commitment to understand how sex differences affect brain aging and risk of Alzheimer’s disease.
Alzheimer’s disease is the most common form of dementia and the sixth leading cause of death in the United States, affecting 5.6 million Americans regardless of ethnic and cultural background. The number of persons living with Alzheimer’s is projected to nearly triple by 2050. Currently, there are no therapeutics to prevent, delay or reverse late-onset AD, leading to a host of possible reasons behind the failed clinical trials; one of the most far-reaching is the sex differences in the underlying mechanisms leading to Alzheimer’s. There is growing consensus that, to stem the AD epidemic, sex-specific interventions that can potentially slow or reverse the trajectory of AD earlier in the course of the disease will be required.
Notably, women are at the epicenter of the AD epidemic. Of every three AD patients, two are women, even after accounting for their greater longevity relative to men. The onset of menopause further increases risk, with postmenopausal women accounting for over 60% of all those affected. Despite the well-established vulnerability of women to AD, there is a striking absence of knowledge on how and why AD affects women more than men, and how to intervene to reduce the risk.
Our brain imaging studies implicate the menopause transition as an early initiating risk factor for Alzheimer’s in women. While the menopause is typically associated with reproductive senescence, it is the dysregulation of brain estrogen-regulated systems that produces the key neurological symptoms of menopause, including hot flashes, disturbed sleep, depression, and memory decline. Overall, these data point to an underwritten headline: the decline in brainestrogen as a female-specific trigger for Alzheimer’s. As such, as women approach midlife, there seems to be a critical window of opportunity, not only to detect signs of early Alzheimer’s but to then intercede with strategies to reduce or prevent that risk by ameliorating estrogen levels.
Of every 3 Alzheimer's patients, 2 are women. Even after accounting for women's greater longevity than men, women still outnumber men 2:1 in the Alzheimer's population. Our research is devoted to unraveling the causes of the increased risk in women. As a starting point, our brain imaging studies have demonstrated a link between estrogen declines and increased Alzheimer's risk in women. Our current NIH-sponsored brain imaging research builds upon those findings to further address the connections between female sex hormones, brain aging, and Alzheimer's risk.
As with any research study, only eligible participants can enroll. At the moment, we are enrolling women and men of age 40-65 years, with a family history of Alzheimer's, and no cognitive impairment or dementia.
If you are eligible and interested in participating in the WBI, we would be happy to provide more details about the study. Please contact firstname.lastname@example.org for more information.
Hollie Hristov, FNP
Director of Clinical Operations at the WBI, and family nurse practitioner at the Alzheimer's Prevention Clinic.
Silky Pahlajani, MD
Dr. Pahlajani Assistant Professor of Behavioral Neurology and Neuropsychiatry.
Harini Sarva, MD
Dr. Sarva specialist in Parkinson's disease and movement disorders, and a study physician for the WBI.
Andrea Lee, MD
Dr. Lee specialist in Parkinson’s disease and movement disorders, and study physician for the WBI.
Eva Schelbaum, MA
Steven Jett, MA
Lacey Loughlin, MA
Aneela Rahman, PhD Student
Senior Study Coordinator.
Nabeel Saif, MS
Hande Jackson, MA
Ivan Diaz, PhD
Senior Biostatistician for the WBI.
Katherine Hoffman, MS
Biostatistician for the WBI.
Roberta Diaz Brinton, PhD
Director of the Center for Innovation in Brain Science at the University of Arizona, Dr. Brinton is a leading neuroscientist in the field of Alzheimer’s, the aging female brain and regenerative therapeutics.
Claire Henchcliffe, MD
Claire Henchcliffe, MD, Associate Professor of Neuroscience at Weill Cornell, Director of the Parkinson’s Institute, and Vice Chair for Clinical Research in Neurology
Orli R. Etingin, MD
Orli Etingin, Professor of Medicine in Clinical Obstetrics and Gynecology, Lisa and Sanford B. Ehrenkranz Professor in Women’s Health at Weill Cornell Medical College, founder and director of the WCMC Iris Cantor Women’s Health Center.
Susan Gauthier, MD
Susan Gauthier, Associate Professor of Clinical Neurology and the Director of Clinical Research at the Weill Cornell Multiple Sclerosis Center.
Teena Shetty, MD
Founder and Director of the Hospital for Special Surgery Concussion Program and Assistant Professor of Clinical Neurology at Weill Cornell Medical College.
John Babich, PhD, Professor of Radiology and Chief of Radiochemistry at Weill Cornell, focuses on the use of radiolabeled small molecules for molecular imaging.
Director of the BODy lab at NYU Medical Center, Dr. Convit is an expert in the impact of metabolic disorders on cognition and brain integrity.
Jonathan Dyke, PhD
Dr. Dyke, Associate Professor of Radiology with over 20 years’ experience, provides expertise in MRI and PET image acquisition and analysis.
Professor of Clinical Pathophysiology at University of Florence Medical College, Dr. Pupi is an internationally acclaimed expert in Positron Emission Tomography (PET) and SPECT.
The Weill Cornell Women’s Brain Initiative is funded by the National Institute of Health/National Institute on Aging (NIH/NIA) grants 2P01AG026572-11, S2P01AG026572-13S1, AG057931; AG057931-01A1; National Center for Advancing Translational Sciences (NCATS) grant UL1TR002384, the Cure Alzheimer’s Fund; Maria Shriver’s Women’s Alzheimer’s Movement; departmental funding; and private donations.
Publications (selected from over 100)
Isaacson RS, Hristov H, Saif N, Hackett K, Hendrix S, Melendez J, Safdieh J, Fink M, Thambisetty M, Sadek G, Bellara S, Lee P, Berkowitz C, Rahman A, Meléndez-Cabrero J, Caesar E, Cohen R, Lu PL, Dickson SP, Hwang MJ, Scheyer O, Mureb M, Schelke MW, Niotis K, Greer CE, Attia P, Mosconi L, Krikorian R.
Individualized clinical management of patients at risk for Alzheimer's dementia. Journal of Alzheimer’s & Dementia 2019; 1552-5260. https://doi.org/10.1016/j.jalz.2019.08.198.
Mosconi L, Brinton RD. How would we combat menopause as an Alzheimer’s disease risk factor? Expert Reviews of Neurotherapeutics (editorial) 2018;18:689-691. https://www.ncbi.nlm.nih.gov/pubmed/30091648
Scheyer O, Rahman A, Webb H, Brinton RD, Isaacson RS,Mosconi L. The menopause transition: a female-specific risk factor for Alzheimer’s disease. Journal of Prevention of Alzheimer’s Disease 2018;5:225-230. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198681/
Mosconi L, Rahman A, Diaz I, Scheyer O, Xian W, Webb H, Vallabhajosula S, Isaacson RS, de Leon MJ, Brinton RD. The perimenopause to menopause transition influences Alzheimer’s biomarker progression: a 3-year brain imaging study. PLOS One 2018; in press. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207885
Berti V, Walters M, Sterling J, Quinn C, Davies M, Andrews R, Matthews DC, Pupi A, Osorio R, Matthews DC, Vallabhajosula S, Isaacson RS, de Leon MJ, Mosconi L. Mediterranean diet and 3-year brain imaging changes in young to late middle-aged adults at risk for Alzheimer’s disease. https://www.ncbi.nlm.nih.gov/pubmed/29653991
Walters M, Sterling J, Quinn C, McHugh P, Andrews R, Matthews DC, Ganzer C, Osorio R, Ganzer C, Vallabhajosula S, Isaacson RS, de Leon MJ, Mosconi L. Associations of lifestyle and vascular risk factors with Alzheimer’s brain biomarker changes during middle age: a 3-year longitudinal study in the broader New York City area. British Medical Journal 2018;8(11):e023664; in press. https://www.ncbi.nlm.nih.gov/pubmed/30478117
Mosconi L, Walters M, Sterling J, Quinn C, McHugh P, Andrews R, Matthews DC, Ganzer C, Osorio R, Isaacson RS, de Leon MJ, Convit A. Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer’s disease: a cross-sectional study of middle-aged adults from the broader New York City area. British Medical Journal (open access) 2018; 8(3):e019362. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875649/
Mosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Pupi A, Osorio R, Isaacson RS, Vallabhajosula S, de Leon MJ, Brinton RD. Altered Brain bioenergetics in the Perimenopause to Menopause transition: Implications for the increased Alzheimer’s risk in women. PLOS One 2017; 12: e0185926. https://www.ncbi.nlm.nih.gov/pubmed/29016679
Mosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Varsavsky I, Osorio RS, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Brinton RD. Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronological aging. Neurology 2017; 89:1382-1390. https://www.ncbi.nlm.nih.gov/pubmed/28855400
Mosconi L, Murray J, Davies M, Williams S, Pirraglia E, Spector N, Tsui WH, Li Y, Butler T, Osorio R, Glodzik L, Vallabhajosula S, McHugh P, Marmar CR, de Leon MJ. Nutrient intake and brain biomarkers of Alzheimer’s disease in at-risk cognitively normal individuals: a cross-sectional neuroimaging pilot study. British Medical Journal 2014; 4:e004850. https://www.ncbi.nlm.nih.gov/pubmed/24961717
Berti V, Murray J, Davies M, Spector N, Tsui WH, Li Y, WilliamsS, Pirraglia E, Vallabhajosula S, McHugh P, Pupi A, de Leon MJ, Mosconi L. Nutrient patterns and brain biomarkers of Alzheimer’s disease in cognitively normal individuals. Journal of Nutrition Health and Aging 2014; 19:413-423. https://www.ncbi.nlm.nih.gov/pubmed/25809805
Mosconi L, Murray J, Tsui WH, Li Y, Davies M, Williams S, Pirraglia E, Spector N, Osorio R, Glodzik L, McHugh P, de Leon MJ. Mediterranean diet and Magnetic Resonance Imaging-assessed brain atrophy in cognitively normal individuals at risk for Alzheimer’s disease. Journal of Prevention of Alzheimer’s disease 2014; 1: 23-32. https://www.ncbi.nlm.nih.gov/pubmed/25237654
Mosconi L, Murray J, Tsui WH, Li Y, Spector N, Goldowsky A, Williams S, Osorio R, McHugh P, Glodzik L, Vallabhajosula S, de Leon MJ. Brain imaging of cognitively individuals with two late-onset Alzheimer’s parents. Neurology 2014; 82:752-60. https://www.ncbi.nlm.nih.gov/pubmed/24523481
Mosconi L, Rinne JO, Tsui WH, Murray J, Li Y, Glodzik L, McHugh P, Williams S, Cummings M, Pirraglia E, Goldsmith SJ, Vallabhajosula S, Scheinin N, Viljanen T, Nagren K, de Leon MJ. Amyloid and metabolic PET imaging of cognitively normal adults with Alzheimer’s parents. Neurobiology of Aging 2013; 34:22-34. https://www.ncbi.nlm.nih.gov/pubmed/22503001
Mosconi L, Tsui W, Murray J, McHugh P, Li Y, Williams S, Pirraglia E, Glodzik L, De Santi S, Vallabhajosula S, de Leon MJ. Maternal age affects brain metabolism in adult children of mothers affected by Alzheimer’s disease. Neurobiology of Aging 2012; 33:624.e1-642.e9. https://www.ncbi.nlm.nih.gov/pubmed/21514691
Mosconi L, de Leon MJ, Murray J, E L, J Lu, Javier E, McHugh P, Swerdlow RH. Reduced cytochrome oxidase activity in adult children of mothers with Alzheimer’s disease. Journal of Alzheimer’s disease 2011, 27:483-490. https://www.ncbi.nlm.nih.gov/pubmed/21841246
Mosconi L, Glodzik L, Mistur R, McHugh P, Rich KE, Javier E, Williams S, Pirraglia E, De Santi S, Mehta PD, Zinkowski R, Blennow K, Pratico D, de Leon MJ. Oxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer’s. Biological Psychiatry, 2010; 68:913-921. https://www.ncbi.nlm.nih.gov/pubmed/20817151
Mosconi L, Rinne JO, Tsui W, Berti V, Li Y, Murray J, Wang H, Scheinin N, Någren K, Williams S, Glodzik L, De Santi S, Vallabhajosula S, de Leon MJ. Increased fibrillar amyloid-β burden in normal individuals with a family history of late-onset Alzheimer’s. Proceedings of the National Academy of Sciences USA 2010, 107: 5949-54. [Article featured in the “Research Highlights” section of the June issue of Nature Reviews Neurology; Yates D. Alzheimer disease: maternal history of Alzheimer disease correlates with amyloid-beta deposition. Nat Rev Neurol 2010; 6:298] https://www.ncbi.nlm.nih.gov/pubmed/20231448
Mosconi L, Mistur R, Switalski R, Brys M, Glodzik L, Pirraglia E, Tsui WH, De Santi S, de Leon MJ. Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer’s. Neurology 2009; 72:513-20. Epub 2008 Nov 12 [Article featured in the “Highlights” section of the Dec 12th issue of Neurology; Related commentary in Neurology: Dhawan V, Eidelberg D. Mom and me: brain metabolism links Alzheimer disease to maternal genes. Neurology 2009; 72:513-20] https://www.ncbi.nlm.nih.gov/pubmed/19005175
Mosconi L, Brys M, Switalski R, Mistur R, Glodzik L, Pirraglia E, Tsui WH, De Santi S, de Leon MJ. Maternal family history of Alzheimer’s disease predisposes to reduced brain glucose metabolism. Proceedings of the National Academy of Sciences USA 2007; 104:19067-19072. https://www.ncbi.nlm.nih.gov/pubmed/18003925