Untitled Document

Research

Sanjay Asthana

M.D., University of Delhi, New Delhi, India
Professor, Department of Medicine
Section Head, Geriatrics and Gerontology; Director, Geriatric Research, Education and Clinical Center (GRECC);
Associate Director, Wisconsin Alzheimer's Institute
sa@medicine.wisc.edu
http://www2.medicine.wisc.edu/home/people-search/people/staff/2303/ASTHANA_SANJAY/

Estrogen, Cognition and Alzheimer's Disease

The goal of my initial research studies was to evaluate the therapeutic potential of cholinesterase inhibitors and muscarinic agonists for Alzheimer's Disease (AD). Administration of the cholinergic drugs physostigmine and arecoline improved cognitive function of patients with AD. The results of these initial studies also indicated that, in general, cholinergic drugs had short half-lives and were associated with significant adverse effects.

My primary current research objective is to evaluate the therapeutic potential of estrogen and raloxifene for postmenopausal women with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). My preliminary findings suggested that treatment with transdermal estradiol enhanced selective attention and verbal memory for postmenopausal women with AD. Furthermore, the improvement in memory was directly correlated with plasma estradiol levels. In addition to cognition, the results of my studies have characterized the neuroendocrine response to estradiol treatment for older women with AD. It is believed that some of these responses might mediate the cognition-enhancing efficacy of estrogen. The need to evaluate the therapeutic potential of raloxifene for postmenopausal women with AD is critical, as it does not cause cancers of the breast or uterus. Preliminary findings indicated that, like estrogen, raloxifene enhanced selective attention and verbal memory for postmenopausal women with AD, but these improvements were of a smaller magnitude.

Another major objective of my research program is to evaluate the efficacy of gonadal hormones for the treatment of age-associated cognitive deficits as well as those seen in patients with MCI. Preliminary findings indicated that both opposed and unopposed estrogen enhanced cognitive function for healthy older women. Additionally, results of a recent collaborative study suggested that administration of testosterone improved spatial and verbal memory for healthy older men.

Representative Publications
Carlsson, C.M., Gleason, C.E., Puglielli, L., & Asthana, S. (2009). Dementia including Alzheimer�s disease. In J. Halter, J. Ouslander, M. Tinnetti, S. Studenski, & S. Asthana (Eds.), Hazzard�s Geriatric Medicine and Gerontology (6th ed.). New York: McGraw-Hill Professional.

Gleason, C.E., Wharton, W., Carlsson, C.M., & Asthana, S. (2009). Alternative estrogen treatment regimens and the Kronos Early Estrogen Prevention Study-Cognitive and Affective Substudy (KEEPS-CA). In E. Hogervorset, V. Henderson, R. Gibbs, & R. Brintn R. (Eds.), Hormones, Cognition and Dementia: State of the Art and Emergent Therapeutic Strategies. Cambridge, UK: Cambridge University Press.

Wharton, W., Asthana, S., & Gleason, C.E. (2009). Testosterone therapy and Alzheimer�s disease: Potential for treatment and prevention, in Hormones, Cognition and Dementia: State of the Art and Emergent Therapeutic Strategies. In E. Hogervorset, V. Henderson, R. Gibbs, & R. Brintn R. (Eds.), Hormones, Cognition and Dementia: State of the Art and Emergent Therapeutic Strategies. Cambridge, UK: Cambridge University Press.

Wharton, W., Asthana, S., & Gleason, C.E. (2009). The use of transdermal 17 β-estradiol in the treatment of Alzheimer�s disease, in Hormones, Cognition and Dementia: State of the Art and Emergent Therapeutic Strategies. In E. Hogervorset, V. Henderson, R. Gibbs, & R. Brintn R. (Eds.), Hormones, Cognition and Dementia: State of the Art and Emergent Therapeutic Strategies. Cambridge, UK: Cambridge University Press.

Xu, G., McLaren, D.G., Ries, M.L., Fitzgerald, M.E., Bendlin, B.B., Rowley, H.A., Sager, M.A., Atwood, C.S., Asthana, S., & Johnson, S.C. (2009). The influence of parental history of Alzheimer's disease and apolipoprotein E 4 on the BOLD signal during recognition memory. Brain, 132, 383-391.

Asenath, L.R., Hermann, B., Jones, J., Johnson, S.C., Asthana, S., & Sager, M.A. (2008). Effect of family history of Alzheimer�s disease on serial position profiles. Alzheimer�s and Dementia, 4(4), 285-290.

Ertekin-Tanner, N., Younkin, L.H., Yager, D.M., Parfitt, F., Baker, M.C., Asthana, S., Hutton, M.L., Younkin, S.G., & Graff-Radford, N.R. (2008). Genetic elevation of plasma amyloid β levels in typical late-onset Alzheimer�s disease relatives and pedigrees. Neurology, 70(8), 596-606.

Haasl, R.J., Reza Ahmadi, M., Vadakkadath Meethal, S., Gleason, C.E., Johnson, S.C., Asthana, S., Bowen, R.L., & Atwood, C.S. (2008). A luteinizing hormone receptor intronic variant is significantly associated with decreased risk of Alzheimer�s disease in males carrying an apolipoprotein E e4 Allele. BMC Medical Genetics, 9(1), 37.

Hermann, B., Seidenberg, M., Sager, M., Carlsson, C.M., Gidal, B., Sheth, R., Rutecki, P., & Asthana, S. (2008). Growing old with epilepsy: the neglected issue of cognitive and brain health in aging persons with chronic epilepsy. Epilepsia, 49(5), 731-740, 2008.

Ries, M.L., Carlsson, C.M., Rowley, H.R., Sager, M.A., Gleason, C.E., Asthana, S., & Johnson, S.C. (2008). MRI characterization of brain structure and function in Mild Cognitive Impairment: A review. Journal of the American Geriatrics Society, 56(5), 920-934.

Xu, G., Fitzgerald, M.E., Wen, Z., Fein, S., Alsop, D., Carroll, T., Ries, M., Rowley, H., Sager, M., Asthana, S., Johnson, S.C., & Carlsson, C.M. (2008). Atorvastatin therapy is associated with greater and faster cerebral hemodynamic response. Brain Imaging and Behavior, 2(2), 94-104.

Johnson, S.C., Schmitz, T.W., Asthana, S., Gluck, M.A., & Myers, C.E. (2008). Associative learning over trials activates the hippocampus in healthy elderly but not mild cognitive impairment. Aging, Neuropsychology, and Cognition, 15, 129-14.

Carlsson, C.M., Gleason, C.E., Hess, T.M., Moreland, K.A., Blazel, H.M., Koscik, R.L., Schreiber, N.T.N., Johnson, S.C., Atwood, C.S., Puglielli, L., Hermann, B.P., McBride, P.E., Stein, J.H., Sager, M.A., & Asthana, S. (2008). Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimers disease. Journal of Alzheimers Disease, 13(2), 187-97.

Trivedi, M.A., Schmitz, T.W., Ries, M.L., Hess, T.M., Fitzgerald, M.E., Atwood, C.S., Rowley, H.A., Asthana, S., Sager, M.A., & Johnson, S.C. (2008). fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: Risk factors for Alzheimer's disease. Neuropsychologia, 46(6), 1667-1678.

Johnson, S.C., Ries, M.L., Hess, T.M., Carlsson, C.M., Gleason, C.E., Alexander, A.L., Rowley, H.A., Asthana, S., & Sager, M.A. (2007). Effect of Alzheimer disease risk on brain function during self-appraisal in healthy middle-aged adults. Archives of General Psychiatry, 64(10), 1163-1171.

Ries, M.L., Jabbar, B.M., Schmitz, T.W., Trivedi, M.A., Gleason, C.M., Rowley, H.A., Asthana, S., & Johnson, S.C. (2007). Anosognosia in MCI: Relationship to activation of cortical midline structures involved in self-appraisal. Journal of the International Neuropsychological Society, 13, 450-61.

Trivedi, M.A., Schmitz, T.W., Ries, M.L., Torgerson, B.M., Sager, M.A., Hermann, B.P., Asthana, S., & Johnson, S.C. (2006). Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk for Alzheimer�s Disease: a cross-sectional study. BMC Medicine, 4, 1.

Gleason, C.E., Schmitz, T.W., Hess, T., Koscik, R.L., Trivedi, M.A., Ries, M.L., Carlsson, C.M., Sager, M.A., Asthana, S., & Johnson, S.C. (2006). Hormone effects on fMRI and cognitive measures of encoding: Importance of hormone preparation. Neurology, 67, 2039-204.

Johnson, S.C., Schmitz, T.W., Moritz, C.H., Meyerand, M.E., Rowley, H.A., Alexander, A.L., Hansen, K.W., Gleason, C.E., Carlsson, C.M., Ries, M.L., Asthana, S., Chen, K., Reiman, E.M., & Alexander, G.E. (2006). Activation of brain regions vulnerable to Alzheimer�s disease: The effect of mild cognitive impairment. Neurobiology of Aging, 27, 1604-161.

Johnson, S.C., Schmitz, T.W., Trivedi, M.A., Ries, M.L., Torgerson, B.M., Carlsson, C.M., Asthana, S., Hermann, B.P., & Sager, M.A. (2006). The influence of AD family history and APOE4 on mesial temporal lobe activation. Journal of Neuroscience, 26, 6069-607.

Gleason, C.E., Cholerton, B., Carlsson, C.M., Johnson, S.C., & Asthana, S. (2005). Neuroprotective effects of female sex steroids in humans: Current controversies and future directions. Cell. Mol. Life Sci., 62(3), 299-312.

Gleason, C.E., Carlsson, C.M., Johnson, S.C., Atwood, C., & Asthana, S. (2005). Clinical pharmacology and differential cognitive efficacy of estrogen preparations. Annals of the New York Academy of Science, 1052, 93-115.

Cholerton, B., Gleason, C., Baker, L.D., & Asthana, S. (2002). Estrogen and Alzheimer's disease: The story so far. Drugs and Aging, 19(6), 405-427.

Asthana, S., Baker, L.D., Craft, S., Stanczyk, F.Z., Veith, R.C., Raskind, M.A., & Plymate, S.R. (2001). High-dose estradiol improves cognition for women with Alzheimer's disease: Results of a randomized study. Neurology, 57, 605-612.

Cherrier, M., Asthana, S., Plymate, S., Baker, L.D., Matsumoto, A.M., Peskind, E., & Raskind, M.A., et al. (2001). Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology, 57, 80-88.

Craft, S., Asthana, S., Schellenberg, G., Baker, L.D., Cherrier, M., Boyt, A.A., Martins, R.N., et al. (2000). Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype. Annals NY Acad. Sci., 903, 222-228.

Asthana, S., Raffaele, K.C., Greig, N.H., Berardi, A., Schapiro, M.B., Blackman, M.R., & Soncrant, T.T. (1999). Neuroendocrine responses to intravenous infusion of physostigmine in patients with alzheimer's disease. Alz. Dis. Assoc. Disord., 13(2), 102-108.

Asthana, S., Craft, S., Baker, L.D., Raskind, M.A., Avery, E., Lofgreen, C., Veith, R.C., & Plymate, S.R. (1999). Cognitive and neuroendocrine response to transdermal estrogen in women with Alzheimer's disease: Results of a randomized, placebo-controlled pilot study. Psychoneuroendocrinology, 24(6), 657-678.

Craft, S., Asthana, S., Newcomer, J.W., Wilkinson, C.W., Baker, L.D., Cherrier, M., Tio-Mattis, I., et al. (1999). Enhancement of memory in Alzheimer's disease with insulin and somatostatin, but not glucose. Arch. Gen. Psychiatry, 56, 1135-1140.

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