Effects of estrogen on cognition, mood, and cerebral blood flow in AD

Objective: To examine the effects of estrogen therapy on cognition, mood, and cerebral blood flow in patients with AD. Background: Some studies have suggested estrogen may be effective in the treatment of AD. However, most of these studies were not controlled adequately. Methods: Fifty female AD patients were recruited in a randomized, double-blind, placebo-controlled 12-week trial. Each member of the estrogen-treated group received conjugated estrogen (Premarin) 1.25 mg/day. The primary outcome measures were the Cognitive Ability Screening Instrument (CASI), Clinical Dementia Rating (CDR), and Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary outcome measures were Behavioral Pathology in Alzheimer’s Disease (BEHAVE-AD), Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale (HDRS), and 99mTc hexamethylpropylene amine oxime SPECT of the brain. Results: No meaningful differences were found between the outcome measures (CASI, CDR, CIBIC-plus, BEHAVE-AD, HARS, HDRS, and cerebral blood flow) taken from the estrogen-treated group and those from the control group. Conclusion: A 1.25-mg/day dose of Premarin administered for 12 consecutive weeks does not produce a meaningful effect on cognitive performance, dementia severity, behavior, mood, and cerebral perfusion in female AD patients. Because estrogen therapy has been suspected of yielding adverse effects, and its therapeutic effectiveness is in doubt, additional evaluation of its role in AD treatment ought to be conducted.

[1]  J. Kitawaki,et al.  Serum and urinary oestrone sulphate in pregnancy and delivery measured by a direct radioimmunoassay. , 1986, Acta endocrinologica.

[2]  J. J. Smith,et al.  Estrogen inhibits the response-to-injury in a mouse carotid artery model. , 1995, The Journal of clinical investigation.

[3]  V. Luine.  Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats , 1985, Experimental Neurology.

[4]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[5]  N. Hagino,et al.  Evaluation of estrogen treatment in female patients with dementia of the Alzheimer type. , 1994, Endocrine journal.

[6]  Nambara Toshio,et al.  In vivo effects by estrone sulfate on the central nervous system-senile dementia (Alzheimer's type). , 1989 .

[7]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[8]  Yaakov Stern,et al.  Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease , 1996, The Lancet.

[9]  L. Schneider,et al.  Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer's disease , 1996, Neurology.

[10]  D. Kiel,et al.  The effect of postmenopausal estrogen therapy on bone density in elderly women. , 1993, The New England journal of medicine.

[11]  T. Yonezawa,et al.  In vivo effects by estrone sulfate on the central nervous system-senile dementia (Alzheimer's type). , 1989, Journal of steroid biochemistry.

[12]  J. Yesavage,et al.  Estrogen replacement therapy and memory in older women. , 1995, Journal of the American Geriatrics Society.

[13]  J. Morris,et al.  Validity and Reliability of the Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change , 2017 .

[14]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[15]  Bruce S. McEwen,et al.  Estradiol and progesterone regulate neuronal structure and synaptic connectivity in adult as well as developing brain , 1994, Experimental Gerontology.

[16]  E. Larson,et al.  Cognitive decline and Japanese culture in a cohort of older Japanese Americans in King County, WA: the Kame Project. , 1999, The journals of gerontology. Series B, Psychological sciences and social sciences.

[17]  C. P. Hughes,et al.  A New Clinical Scale for the Staging of Dementia , 1982, British Journal of Psychiatry.

[18]  M. D. O'Brien,et al.  Cerebral blood flow in dementia , 1986, Neurology.

[19]  S. Campbell,et al.  Oestrogen therapy and the menopausal syndrome. , 1969, Clinics in obstetrics and gynaecology.

[20]  B. Sherwin,et al.  Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women , 1988, Psychoneuroendocrinology.

[21]  B. Sherwin,et al.  Effects of estrogen on memory function in surgically menopausal women , 1992, Psychoneuroendocrinology.

[22]  P. Greengard,et al.  Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. , 1994, The Journal of biological chemistry.

[23]  W. Hazzard,et al.  Lipoprotein, apolipoprotein, and lipolytic enzyme changes following estrogen administration in postmenopausal women. , 1989, Journal of lipid research.

[24]  J. Galen Buckwalter,et al.  Cognitive skills associated with estrogen replacement in women with Alzheimer's disease , 1996, Psychoneuroendocrinology.

[25]  S H Ferris,et al.  Behavioral symptoms in Alzheimer's disease: phenomenology and treatment. , 1987, The Journal of clinical psychiatry.

[26]  K. Yaffe,et al.  Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. , 1998, JAMA.

[27]  M. Hamilton.  The assessment of anxiety states by rating. , 1959, The British journal of medical psychology.

[28]  M. Serio,et al.  A RAPID RADIOIMMUNOASSAY FOR DETERMINATION OF DEHYDROEPIANDROSTERONE SULPHATE IN HUMAN PLASMA , 1975, Clinical endocrinology.

[29]  N. Hagino,et al.  Long-term estrogen replacement therapy in female patients with dementia of the Alzheimer type: 7 case reports. , 1995, Dementia.

[30]  H C Liu,et al.  Prevalence and Subtypes of Dementia in a Rural Chinese Population , 1998, Alzheimer disease and associated disorders.

[31]  Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study. , 1991 .

[32]  H. Fillit,et al.  Observations in a preliminary open trial of estradiol therapy for senile dementia-alzheimer's type , 1986, Psychoneuroendocrinology.

[33]  R. Lobo,et al.  Estrogen Improves Psychological Function in Asymptomatic Postmenopausal Women , 1991, Obstetrics and gynecology.

[34]  R. Brookmeyer,et al.  A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease , 1997, Neurology.

[35]  S. Resnick,et al.  Estrogen replacement therapy and longitudinal decline in visual memory , 1997, Neurology.