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WAI Faculty & Staff

Mark Sager, MD


Contact Information

Phone: 608-829-3304
Mailing address: Wisconsin Alzheimer's Institute, UW School of Medicine and Public Health, 7818 Big Sky Drive, Suite 215, Madison, WI 53719


Chief of Operations, Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health

Professor Emeritus, University of Wisconsin School of Medicine and Public Health, Madison



B.S., 1968 Chemistry and Biology, University of Illinois (Champaign); M.D., 1972 University of Michigan; Residency, 1972-1975, Internal Medicine, University of Minnesota; 1985-1987, Geriatrics Fellowship, University of Wisconsin-Madison



Dr. Sager is Chief of Operations, Professor Emeritus at the University of Wisconsin-Madison School of Medicine and Public Health and former Director of the Wisconsin Alzheimer's Institute. He is the founder of the Wisconsin Registry for Alzheimer's Prevention (WRAP) which is a longitudinal study of adult children of persons with Alzheimer's disease. The primary goal of WRAP is to conduct genetic, epidemiological and clinical research that could lead to the prevention of Alzheimer's disease. Dr. Sager also developed the WAI affiliated network of dementia diagnostic clinics consisting of Wisconsin physicians and health care providers dedicated to improving the care provided to persons with Alzheimer's disease and their families. He is a fellowship trained geriatrician and received his MD from the University of Michigan. Dr. Sager joined the UW faculty in 1992.


Research Interests

Alzheimer's disease prevention; Improving quality of care in long term care


Research Description

The proportion of the population aged 65 and older is projected to increase from 13% in 2000 to 20% by 2030, primarily because of the aging of the baby boom generation and increased longevity. Persons aged 85 and older (the oldest old) will represent an increasing proportion of this aging population and an estimated 40% of persons turning 65 in 2000 will survive to the age of 85 years. The implications of this aging phenomenon for the delivery and financing of long-term care will be especially profound because the oldest old are the largest consumers of long-term care services and one-half of them will develop Alzheimer's disease.


Alzheimer's disease currently affects between 5-10% of the population aged 65 and older and is the most frequent cause of institutionalization for long-term care in the United States. An estimated $2 billion of public and private dollars is spent each year in Wisconsin for nursing home care alone, and almost half of that is to provide care for persons suffering from Alzheimer's disease and related dementias. In Wisconsin, the number of affected persons is expected to increase by 58% from 103,000 to 163,000 persons over the next 25 years. The expected rapid increase in the number of persons with Alzheimer's disease will translate into higher public and private long-term care costs that will be paid by private payers, state Medicaid programs and long-term care insurers. One way to reduce the cost of long-term care is to lower the need for long-term care by delaying the onset or slowing the progression of Alzheimer's disease. Estimates are that a delay in the onset of Alzheimer's disease by five years would result in a 50% reduction in prevalence in one generation. A 10-year delay in the onset of Alzheimer's disease would result in only 3.5 million affected persons by 2040 instead of the anticipated 14 million persons.


Current data indicate that Alzheimer's disease is a lifelong disease with a prolonged pre-clinical phase during which prevention strategies would be most effective in delaying or preventing the onset of Alzheimer's disease. Neuritic plaques and neurofibrillary tangles, the pathological hallmarks of Alzheimer's disease, have been found in adults without dementia, suggesting that the neuronal deficits leading to Alzheimer's disease begin years before any symptoms develop. Other studies have found metabolic and structural changes, typical for Alzheimer's disease, in the brains of asymptomatic middle aged persons. As in other chronic degenerative diseases of aging, a person's risk of developing symptoms of Alzheimer's disease is most likely the result of genetic, environmental, socioeconomic and lifestyle factors which interact to determine age of onset. Because of this, a person's risk of developing symptoms of Alzheimer's disease is potentially modifiable either by changes in the environment or lifestyle or through external interventions.


Dr. Sager's research interests are in identifying ways to delay the onset or slow the progression of Alzheimer's disease using the latest knowledge and technologies available. He is also committed to developing programs that promote: early diagnosis and treatment of persons with Alzheimer's disease; improved quality of care for persons with Alzheimer's disease; and recognition of the unique needs of families and caregivers of persons with Alzheimer's disease.


Representative Publications

(2008 to present)
  1. Carlsson CM, Gleason CE, Hess TM, Arnold K, Blazel HM, Koscik R, Schreiber N, Johnson SC, Atwood CS, Puglielli L, Hermann BP, McBride PE, Stein JH, Sager MA, Asthana S (2008).  Effects of simvastatin on cerebral spinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer’s disease.  Journal of Alzheimer’s Disease, 13(2), 187-97.
  2. Jarvik L, La Rue A, Blacker D, Gatz M, Kawas C, McArdle JJ, Morris JC, Mortimer JA, Ringman JM, Ercoli L, Freimer N, Gokhman I, Manly JJ, Plassman BL, Rasgon N, Roberts JS, Sunderland T, Swan GE, Wolf PA, Zonderman AB (2008).  Children of persons with Alzheimer disease: what does the future hold?  Alzheimer Disease and Associated Disorders, 22(1), 6-20. PMCID: PMC3377487
  3. La Rue A, Hermann B, Jones JE, Johnson S, Asthana S, Sager MA (2008). Effect of parental family history of Alzheimer's disease on serial position profiles. Alzheimers and Dementia: The Journal of the Alzheimer’s Association, 4(4), 285-290. PMCID: PMC2713600.
  4. Trivedi MA, Schmitz TW, Ries ML, Hess TM, Fitzgerald ME, Atwood CS, Rowley HA, Asthana S, Sager MA, Johnson SC (2008). fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: Risk factors for Alzheimer's disease.  Neuropsychologia, 46(6), 1667-78. PMCID: PMC2443867
  5. Xu G, Fitzgerald ME, Wen Z, Fain SB, Alsop DC, Carroll T, Ries ML, Rowley HA, Sager MA, Asthana S, Johnson SC, Carlsson CM (2008). Atorvastatin therapy is associated with greater and faster cerebral hemodynamic response. Brain Imaging and Behavior, 2(2), 94.  PMCID: PMC2821154
  6. Carlsson CM, Nondahl DM, Klein BEK, McBride PE, Sager MA, Schubert C, Klein R, Cruickshanks KJ (2009). Increased atherogenic lipoproteins are associated with cognitive impairment: effects of statins and sub-clinical atherosclerosis. Alzheimer Disease and Associated Disorders, 23(1), 11-17. PMCID: PMC2662715
  7. Xu G, McLaren DG, Ries ML, Fitzgerald ME, Bendlin BB, Rowley HA, Sager MA, Atwood CS, Asthana S, Johnson SC (2009). The influence of parental history of Alzheimer’s disease and apolipoprotein E ε4 on the BOLD signal during recognition memory. Brain, 132(Pt 2), 383-391. PMCID: PMC2724919
  8. Bendlin BB, Ries ML, Canu E, Sodhi A, Lazar M, Alexander AL, Carlsson CM, Sager MA, Asthana S, Johnson SC (2010).  White matter is altered with parental family history of Alzheimer’s disease.  Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 6(5), 394-403. PMCID: PMC2933285
  9. Bendlin BB, Newman LM, Ries ML, Puglielli L, Carlsson CM, Sager MA, Rowley HA, Gallagher CL, Willette AA, Alexander AL, Asthana S, Johnson SC (2010). NSAIDs may protect against age-related brain atrophy.  Frontiers in Aging Neuroscience, Sep 3;2. pii: 35.  PMCID: PMC2944647
  10. Dowling NM, Hermann BP, La Rue A, Sager MA (2010).  Latent structure and factorial invariance of a neuropsychological test battery for the study of preclinical Alzheimer’s disease.  Neuropsychology, 24(6), 742-56. PMCID: PMC3057903
  11. Ward MA, Bendlin BB, McLaren DG, Hess TM, Gallagher CL, Kastman EK, Rowley HA, Asthana S, Carlsson CM, Sager MA, Johnson SC (2010).  Low HDL cholesterol is associated with lower gray matter volume in cognitively healthy adults. Frontiers in Aging Neuroscience, 2(29), 1-8. PMCID: PMC2914583
  12. Johnson SC, La Rue A, Hermann BP, Xu G, Koscik RL, Jonaitis EM, Bendlin BB, Roses AD, Saunders AM, Lutz MW, Asthana S, Green RC, Sager MA (2011). The Effect of TOMM40 Poly-T length on gray matter volume and cognition in middle-aged persons with APOE ε3/ ε3 genotype. Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, 7(4), 456-65. PMCID: PMC3143375
  13. Bendlin BB, Carlsson CM, Johnson SC, Zetterberg H, Blennow K, Willette AA, Okonkwo OC, Sodhi A, Ries ML, Birdsill AC, Alexander AL, Rowley HA, Puglielli L, Asthana A, Sager MA (2012).  CSF t-tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer’s disease.  PLoS ONE, 7(6), e37720.  PMCID: PMC3368882
  14. Carlsson CM, Xu G, Wen Z, Barnet JH, Blazel HM, Chappell RJ, Stein JH, Asthana S, Sager MA, Alsop DC, Rowley HA, Fain SB, Johnson SC (2012).  Effects of atorvastatin on cerebral blood flow in middle-aged adults at risk for Alzheimer's disease: A Pilot Study.  Current Alzheimer Research, 9(8), 990-7. PMCID: PMC3576818
  15. Chang TS, Coen MH, La Rue A, Jonaitis EM, Koscik RL, Hermann BP, Sager MA (2012).  Machine learning amplifies the effect of parental family history of Alzheimer's disease on list learning strategy.  Journal of the International Neuropsychological Society, 18(3), 428-39. PMCID: PMC3348337
  16. Okonkwo O, Xu G, Dowling M, Bendlin BB, La Rue A, Herman BP, Koscik RL, Jonaitis EM, Rowley H, Carlsson CM, Asthana S, Sager MA, & Johnson SC (2012). Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults. Neurology, 78(22), 1769-76. PMCID: PMC3359586
  17. Okonkwo OC, Xu G, Oh JM, Dowling NM, Carlsson CM, Gallagher CL, Birdsill AC, Palotti M, Wharton W, Hermann BP, Larue A, Bendlin BB, Rowley HA, Asthana S, Sager MA, Johnson SC (2012). Cerebral blood flow is diminished in asymptomatic middle-aged adults with maternal history of Alzheimer's disease. Cereb Cortex, 24(4), 978-988. PMID: 23236200. PMCID: PMC3948496
  18. Ries ML, McLaren DG, Bendlin BB, Xu G, Rowley HA, Birn R, Kastman EK, Sager MA, Asthana S, Johnson SC (2012).  Medial prefrontal functional connectivity: relation to memory self-appraisal accuracy in older adults with and without memory disorders.  Neuropsychologia, 50(5), 603-611. PMCID: PMC3537182
  19. Wharton W, Stein JH, Korcarz C, Sachs J, Olson SR, Zetterberg H, Dowling M, Ye S, Gleason CE, Underbakke G, Jacobson LE, Johnson SC, Sager MA, Asthana S, Carlsson CM (2012). The Effects of Ramipril in Individuals at Risk for Alzheimer’s Disease: Results of a Pilot Clinical Trial. Journal of Alzheimer's disease: J Alzheimers Dis, 32(1), 147-56. PMCID:  PMC3593582
  20. Birdsill AC, Carlsson CM, Willette AW, Okonkwo OC, Johnson SC, Xu G, Oh JM, Gallagher CL, Koscik RL, Jonaitis EM, Hermann BP, LaRue A, Rowley HA, Asthana S, Sager MA, Bendlin BB (2013). Low cerebral blood flow is associated with lower memory function in metabolic syndrome. Obesity, 21(7), 1313-20.  PMCID: PMC3742665
  21. Engelman CD, Koscik RL, Jonaitis EM, Okonkwo OC, Hermann BP, La Rue A, Sager MA (2013). Interaction between two cholesterol metabolism genes influences memory: findings from the Wisconsin registry for Alzheimer's prevention. J Alzheimers Dis, 36(4), 749-57. PMCID: PMC3759032
  22. Jonaitis E, La Rue A, Mueller KD, Koscik RL, Hermann B, Sager MA. Cognitive activities and cognitive performance in middle-aged adults at risk for Alzheimer's disease (2013). Psychol Aging. Dec;28(4):1004-14. PMCID: PMC4029346
  23. Willette AA, Xu G, Johnson SC, Birdsill AC, Jonaitis EM, Sager MA, Hermann BP, La Rue A, Asthana S, Bendlin BB (2013). Insulin Resistance, Brain Atrophy, and Cognitive Performance in Late Middle-Aged Adults. Diabetes Care, Feb, 36(2), 443-9. PMCID: PMC3554303
  24. Zuelsdorff ML, Engelman CD, Friedman EM, Koscik RL, Jonaitis EM, Rue AL, Sager MA (2013). Stressful Events, Social Support, and Cognitive Function in Middle-Aged Adults with a Family History of Alzheimer's Disease. J Aging Health. Sep, 25(6), 944-59. PMCID: PMC3769466
  25. Adluru N, Destiche DJ, Lu SY, Doran ST, Birdsill AC, Melah KE, Okonkwo OC, Alexander AL, Dowling NM, Johnson SC, Sager MA, & Bendlin BB. (2014). White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease. Neuroimage Clin, 4, 730-742. PMCID: PMC4053649
  26. Birdsill AC, Koscik RL, Jonaitis EM, Johnson SC, Okonkwo OC, Hermann BP, LaRue A, Sager MA, Bendlin BB (2014). Regional white matter hyperintensities: aging, Alzheimer's disease risk, and cognitive function. Neurobiology of Aging. 35(4):769-76. PMCID: PMC3880609
  27. Boots EA, Schultz SA, Oh JM, Larson J, Edwards D, Cook D, Koscik RL, Dowling MN, Gallagher CL, Carlsson CM, Rowley HA, Bendlin BB, LaRue A, Asthana S, Hermann BP, Sager MA, Johnson SC, & Okonkwo OC (2014). Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer's disease. Brain Imaging Behav. [Epub ahead of print]
  28. Engelman CD, Koscik RL, Jonaitis EM, Hermann BP, La Rue A, Sager MA (2014). Investigation of triggering receptor expressed on myeloid cells 2 variant in the Wisconsin Registry for Alzheimer's Prevention. Neurobiol Aging, 35(6), 1252-4. PMCID: PMC3961539.
  29. Johnson, SC, Christian, BT, Okonkwo, OC, Oh, JM, Harding, S, Xu, G, Hillmer, AT, Wooten, DW, Murali, D, Barnhart, TE, Hall, LT, Racine, AM, Klunk, WE, Mathis, CA, Bendlin, BB, Gallagher, CL, Carlsson, CM, Rowley, HA, Hermann, BP, Dowling, NM, Asthana, S, & Sager, MA (2014). Amyloid burden and neural function in people at risk for Alzheimer's Disease. Neurobiol Aging, 35(3), 576-584. PMCID: PMC4018215
  30. Koscik, RL, La Rue A, Jonaitis, EM, Okonkwo, OC, Johnson, SC, Bendlin, BB, Hermann, BP, & Sager, MA. (2014). Emergence of mild cognitive impairment in late-middle-aged adults in the Wisconsin Registry for Alzheimer’s Prevention. Dementia and Geriatric Cognitive Disorders, 38(1-2), 16-30. PMCID: PMC4104157
  31. Ly M, Canu E, Xu G, McLaren DG, Oh J, Dowling NM, Alexander AL, Sager MA, Johnson SC, Bendlin BB (2014). Midlife measurements of white matter microstructure predict subsequent regional white matter atrophy in healthy adults. Hum Brain Mapp, 35(5), 2044-2054. PMCID: PMC3895105
  32. Mielke, MM, Haughey, NJ, Bandaru, VV, Zetterberg, H, Blennow, K, Andreasson, U, Johnson, SC, Gleason, CE, Blazel, HM, Puglielli, L, Sager, MA, Asthana, S, & Carlsson, CM (2014). Cerebrospinal fluid sphingolipids, beta-amyloid, and tau in adults at risk for Alzheimer's disease. Neurobiol Aging, 35(11), 2486-2494. PMCID: PMC4170854
  33. Nicholas CR, Okonkwo OC, Bendlin BB, Oh JM, Asthana S, Rowley HA, Hermann BP, Sager MA, & Johnson SC (2014). Posteromedial hyperactivation during episodic recognition among people with memory decline: findings from the WRAP study. Brain Imaging Behav. [Epub ahead of print]
  34. Okonkwo OC, Oh JM, Koscik RL, Jonaitis EM, Cleary CA, Dowling NM, Bendlin BB, LaRue A, Hermann BP, Barnhart TE, Murali D, Rowley HA, Carlsson CM, Gallagher CL, Asthana S, Sager MA, Christian BT, Johnson SC (2014). Amyloid burden, neuronal function, and cognitive decline in middle-aged adults at risk for Alzheimer’s disease. Journal of the International Neuropsychological Society, 20(4), 422-433.  PMCID: PMC 4103611
  35. Okonkwo OC, Schultz SA, Oh JM, Larson J, Edwards D, Cook D, Koscik RL, Gallagher CL, Dowling NM, Carlsson CM, Bendlin BB, LaRue A, Rowley HA, Christian BT, Asthana S, Hermann BP, Johnson SC, & Sager MA. (2014). Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology, 83(19), 1753-1760. PMCID: PMC4239838
  36. Racine, AM, Adluru, N, Alexander, AL, Christian, BT, Okonkwo, OC, Oh, J, Cleary, CA, Birdsill, A, Hillmer, AT, Murali, D., Barnhart, T. E., Gallagher, CL, Carlsson, CM, Rowley, HA, Dowling, NM, Asthana, S, Sager, MA, Bendlin, BB, & Johnson, SC (2014). Associations between white matter microstructure and amyloid burden in preclinical Alzheimer's disease: A multimodal imaging investigation. Neuroimage Clin, 4, 604-614. PMCID: PMC405364

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