Hormones Dementia

– Eric R. Braverman, MD
Cognitive decline and development of dementia is now recognized to be multi-factorial. The presence of medical illnesses can damage cognition i.e. atrial fibrillation, diabetes, thyroid disease, heart failure, inflammation, high blood pressure, smoking and other illicit drug use, elevated cholesterol and any cardiac disease or vascular risk factors have all been linked to progression of dementia, which takes at least 10-20 years to develop.


There are at least five stages of cognitive decline prior to dementia with numerous variations. Typically dementia begins with the following order of losses: brain processing speed, memory, attention, personality and temperament change, IQ changes, and ultimately dementia.
Furthermore, numerous studies have linked hormone supplementation as protective in the development of dementia regardless of whether or not these hormones are deficient but more so when they are deficient. Hormonal deficiencies that are linked are: Growth hormone beginning from age 30 in both men and women, estrogen loss beginning at age 40 in women, testosterone loss beginning at age 40 in men and DHEA loss beginning in both men and women at age 50. The loss of luteinizing and sex binding globulin hormones may also be associated with the development of dementia with age.
A wide range of medical and psychiatric illnesses including depression are contributing to the progression of dementia which occurs in most Americans between the ages of 50 and 80 such that 50% of all Americans are fully demented by age 80. Dr. Braverman has identified the marker of the stages of cognitive decline as well as hormonal cornerstone abnormalities associated with most forms of dementia.
INTRODUCTION
Mangone CA., Clinical heterogeneity of Alzheimer’s disease. Different clinical profiles can predict the progression rate, Rev Neurol. 2004 Apr. 1-15; 38(7): 675-81.
Tilvis RS, kahonen-Vare MH, Jolkkonen J, Valvanne J, Pitkala KH, Strandberg TE., Predictors of cognitive decline and morality of aged people over a 10-year period, J Gerontol A Biol. Sci. 2004 Mar;59(3):268-74.
Alison K. Godbolt et al., The natural History of Alzheimer Disease: A longitudinal Presymptomatic and Symptomatic study of a Familial Cohort, 2004;61:1743-17 48.
Kessing LV, Andersen PK., Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder?, J Neurol Neurosurg Psychiatry. 2004 Dec.; 75 (12): 1662-6.
Langa, KM, Norman L. Foster NL, Larson EB, Mixed Dementia Emerging Concepts and Therapeautic Implications,Dec 15, 2004- Vol. 292 No. 23
Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K., Midlife cardiovascular risk factors and risk of dementia in late life., Neurology, 2005 Jan 25;64(2):277-81.
Allen KV, Frier BM, Strachan MW., The relationship between type 2 diabetes and cognitive dysfunction: longitudinal studies and their methodological limitations., Eur J Pharmacol. 2004 Apr.19,490(1-3):169-75.
Kawas CH, Corrada MM, Brookmeyer R, Morrison A, Resnick SM, Zonderman AB, Arenberg D., Visual memory predicts Alzheimer’s disease more than a decade before diagnosis., Neurology. 2003 Apr. 8;60(7): 1089-93.
Messier C, Awad N, Gagnon M., The relationship between atherosclerosis, heart disease, type 2 diabetes and dementia., Neurol Res. 2004 Jul;26 (5):567-72
Kalmijn S, Mehta KM, Pols HA, Horman A, Drexhage HA, Breteler MM., Subclinical hyperthyroidism and the risk of demetia. The Rotterdam study., Clin Endocrinol (Oxf). 2000 Dec;53 (6): 733-7.
ESTROGEN
Henderson VW, Benke KS, Green RC, Cupples LA, Farrer LA; MIRAGE study Group, Post menopausal hormone therapy and Alzheimer’s disease risk: interaction with age, J Neurol Neurosurg Psychiatry. 2005 Jan; 76 (1): 103-5
Henderson VW, Benke KS, Green RC, Cupples LA, Farrer LA; MIRAGE Study Group., J Neurosurg Psychiatry. 2005 Jan; 76 (1): 103-5.
Gleason CE, Cholerton B, Carlsson CM, Johnson SC, Asthma S., Neuroprotective effects of female sex steroids in humans: current controversies abd future directions., Cell Mol Sci. 2005 Feb;62(3):299-312.
Pinkerton JV, Henderson VW., Estrogen and cognition, with a focus on Alzheimer’s disease.,Semin Reprod Med. 2005 May; 23(2):172-9.
Honjo H, Iwasa K, Kawata M, Fushiki S, Hosoda T, Tatsumi H, Oida N, mihara M, Hirasugi Y, Yamamoto H, Kikuchi N, Kitwaki J., Progestins and estrogens and Alzheimer’s disease., Steroid Biochem Mol Biol. 2005 Feb;93(2-5):305-8.
Levine AJ, Battista M., Estrogen replacement therapy: effects on the cognitive functioning and clinical course of women with Alzheimer’s disease., Arch Clin Neuropsychol. 2004Sep;19(6):769-78.
Burkhardt MS, foster JK, Laws SM, Baker LD, Craft S, Grandy SE, Stucky BG, Clarnette R, Nolan D, Hewson-Bower B, Martins Rn., Oestrogen replacement therapy may improve memory functioning in the absence of APOE epsilon4., J Alzheimers Dis. 2004 Jun;6(3):221-8.
TESTOSTERONE
Bates KA, Harvey AR, Carruthers M, Martins RN, Androgens, andropause and neurodengeration: exploring the link between steroidogensis, androgens and Alzheimer’s disease, Cell Mol Life Sci. 2005 Feb; 62(3):281-92.
Bates KA, Harvey AR, Carruthers M, Martins RN, Androgens, andropause and neurodengeration: exploring the link between steroidogensis, androgens and Alzheimer’s disease, Cell Mol Life Sci. 2005 Feb; 62(3):281-92.
Hogervorst E, Bandelow S, Combrink M, Smith AD., Low free testosterone is an independent risk factor for Alzheimer’s disease., Exp Gerontol. 2004 Nov-Dec;39 (11-12):1633-9.
Bremner WJ., Testerone tied to mental function. But question about the benefits and risks of testosterone therapy persist., Health News. 2004 Apr; 10(4): 14-5.
Okun MS, DeLong MR, J, Hanfelt J, Gearing M, Levey A., Plasma testosterone levels in Alzheimer’s and Parkinson diseases., Neurology. 2004 Feb 10;62(3):411-3.
Hoskin EK, Tang MX, manly JJ, Mayeux R., Elevated sex-hormone binding globulin in ederly women with Alzeimer’s disease., Neurobial Aging.2004 Feb;25(2):141-7.
Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman Sm, Resnick SM., Free testosterone and risk for Alzheimer disease in older men. Neurology.2004 Jan27;62(2):188-93.
Henderson VW, Hogervorst E., Testosterone and Alzheimer’s disease: is it men’s turn now?, Neurology.2004 Jan 27;62(2):170-1.
Rosario, Emily MS, Chang Lilly MD. Et al. Age related Testosterone Depletion and the Development of Alzheimer’s Disease. JAMA, Sept 22/29, 2004-Vol. 292, No 12.
Cherrier MM et al. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology. 2005 Jun 28;64(12):2063-8.
DHEA
Leblhuber F, Haller H, Steiner K, Fuchs D., DHEA treatment of Alzheimer’s disease: A randomized, double-blind, placebo controlled trial, Neurology. 2004 Mar 23; 62(6): 1030
Bicikova M, Ripova D, Hill M, Jirak R, Havlikova H, Tallova J, Hampl R., Plasma levels of 7-hydroxylated dehydroepiandrosterone (DHEA) metabolites and selected amino-thiols as discriminatory tools of Alzheimer’s disease and vascular dementia., Clin Chem Lab Med. 2004 May;42(5):518-24.
Yai JL, Rasmuson S, Andrew R, Graham M, Noble J. Olsson T, Fuchs E, Lathe R, Seckl JR., Dehydroepiandrosterone 7-hydroxylase CYP7B: predominant expression in primate hippocampus and reduced expressions in Alzheimer’s disease., Neuroscience.2003;121(2):307-14.
Weill-Engerer S, David JP, Sazdovitch V, Liere P, Eychenne B, Pianos A, Schumacher M, Delacourte A, Baulieu EE, Akwa Y., Neurosteroid quantification in human brain regions: comparison between Alzheimer’s and nondemented patients., J Chin Endocrinol Metab. 2002 Nov;87(11):5138-43.
De Bruin VM, Vieira MC, Rocha MN, Viana GS., Cortisol and dehydropiandosterone sulfate plasma levels and their relationship to aging, cognitive function, and dementia,Brain Cogn. 2002 Nov;50(2):316-23
Brown RC, Han Z, Cascio C, Papadopoulos V., Oxidative stress-mediated DHEA formation in Alzheimer’s disease pathology., Neurobiol Aging.2003 Jan-Feb;24(1): 57-65.
Ravaglia G, Forti P, Maiolo F, Sacchetti L, Nativio V, Scali CR, Mariani E, Zanardi V, Stefanini A, Macini PL., Dehydroepiandrosterone-sulfate serum levels and common age-related disease: results from a cross-sectional Italian study of a general elderly population., Exp Gerontol.2002 May;37(5):701-12.
Armanini D, Vecchio F, Basso A, Milone FF, Simoncini M, Fiore C, Matterello MJ, Sartorato P, Karbowiak I., Alzheimer’s disease: pathophysiological implactions of measurement of plasma cortisol, plasma dehydroepiandrosterone sulfate, and lymphocytic corticosteroid receptors., Endocrine. 2003 Nov;22(2):113-8.
Rasmuson S, Nasman B, Carlstrom K, Olsson T., Increased levels of adrenocortical and gonadal hormones in mild to moderate Alzheimer’s disease.,Dement Geriatr Cogn Disord. 2002;13(2):74-9.
Knopman D, Henderson VW., DHEA for Alzheimer’s disease: a modest showing by a superhormone., Neurology.2003 Apr 8;60(7):1060-1.
GROWTH HORMONES
Mangone CA., Clinical heterogeneity of Alzheimer’s disease. Different clinical profiles can predict the progression rate, Rev Neurol. 2004 Apr 1-15; 38(7): 675-81.
Modrego PJ, Ferrandez J., Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study., Arch Neurol, 2004 Aug;61(8):1290-3.
Mahajan T, Crown A, Checkley S, Farmer A, Lightman S. Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life, European Journal of Endcrinology(2004) 151;235-332.
Pandian R, Nakamoto JM. Rational use of the laboratory for childhood and adult growth hormone deficiency, Clinical lab Med 24 (2004) 14-174
AM Brooke, JP Monson, Adult growth hormone deficiency, Clin Med 2003;3:15-9
Polleri A, Gianelli MV, Murialdo G., Dementia: a neuroendocrine perspective., Endocrinol Invest. 2002 Jan;25(1) 73-83.
Aleman A, Verhaar HJ, De Haan EH, De Vries WR, Samson MM, Drent ML, Van Der Veen EA, Koppeschaar HP., Insulin-like growth factor-I and cognitive function in healthy older men., Clin Endocrinal Metab. 1999 Feb; 84 (2):471-5.
Watanabe T, Yamamoto H, Idei T, Iguchi T, Katagiri T., Influence of insulin-like growth factor-1 and hepatocyte growth factor on carotid atherosclerosis and cognitive function in the elderly., Dement Geriatr Cogn Disord. 2004;18(1):67-74. Epub 2004 Apr 14.
Herrmann N, Lanctot KL, Eryavec G, Van Reekum R, Khan LR., Growth hormone response to clonidine predicts aggression in Alzheimer’s disease., Psychoneuroendocrinology.2004 Oct;29 (9):1192-7.
Schneider HJ, Pagatto U, Stalla GK., Central effects of the somatotropic system., Eur J Endocrinol.2003 Nov;149(5):377-92.
Cordery RJ, Hall M, Cipolotti L, Al-Sarraj S, O’Donovan DG, Davidson L, Adlard P, Rossor MN., Early cognitive decline in Creutzfeldt-Jakob disease associated with human growth hormone treatment.,J Neurol Neurosurg Psychiatry.2003 Oct;74(10):14126.
Hoskin EK, Tang MX, Manly JJ, Mayeux R., Elevated sex-hormone binding globulin in elderly women with Alzheimer’s disease., Neurobiol Aging. 2004 Feb;25(2):141-7.
Bowen RL, Smith MA, Harris PL, Kubat Z, Martins RN, Castellani RJ, Perry G, Atwood CS., Elevated luteinizing hormones expressions colocalizes with neuror vulnerable to Alzheimer’s disease pathology., J Neurosci Res. 2002 Nov. 1;70(3):51 4-8.
Casadesus G, Atwood CS, Zhu X, Hartzler AW, Webber KM, Perry G, Bowen RL< Smith MA., Evidence for the role of gonadotrophin hormones in the development of Alzheimer’s disease., Cell Mol Life Sci. 2005 Feb;62(3):293-8.
Gregory CW, Bowen RL., Novel therapeutic strategies for Alzheimer’s disease based on the forgotten reproductive hormones.. Cell Mol Likfe Sci. 2005 Feb;62(3):313-9.
ADDITIONAL HORMONES
Hoskin EK, Tang MX, Manly JJ, Mayeux R., Elevated sex-hormone binding globulin in elderly women with Alzheimer’s disease., Neurobiol Aging. 2004 Feb; 25(2): 141-7.
Bowen RL, Smith MA, Harris PL, Kubat Z, Martins RN, Castellani RJ, Perry G, Atwood CS., Elevated luteinizing hormone expression colocalized with neuron vulnerable to Alzheimer’s disease pathology., J Neurosci Res. 2002 Nov 1;70(3):514-8.
Casadesus G, Atwood CS, Zhu X, Hartzler AW, Webber KM, Perry G, Atwood CS, Zhu X, Hartzler AW, Webber KM, Perry G, Bowen RL, Smith MA., Evidence for the role of gonadotropin hormones in the development of Alzheimer’s disease., Cell Mol Life Sci. 2005 Feb;62(3):293-8.
Gregory CW Bowen RL, Novel therapeutic strategies for Alzheimer’s disease based on the forgotten reproductive hormones., Cell Mol Life Sci.2005 Feb;62(3):313-9.