Postmenopausal Estrogen Replacement Therapy and the Risk of Alzheimer's Disease: A Population-based Case-Control Study

Brenner, Daniel E.; Kukull, Walter A.; Stergachis, Andy; Belle, Gerald van; Bowen, James D.; McCormick, Wayne C.; Ten, Linda; Larson, Eric B.

doi:10.1093/oxfordjournals.aje.a117245

Cited by 275 publications

(119 citation statements)

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“…The clinical literature generally supports a role of endocrine factors altering AD and other neurodegenerative processes associated with aging. Some, but not all, studies have shown that steroid/E 2 -based therapies to postmenopausal women may attenuate decline in cognitive function, improve mood in AD, and decrease risk for developing AD (Asthana et al 2001;BarrettConnor and Kritz-Silverstein 1993;Brenner et al 1994;Carlson et al 2000;Fillit 2002;Fillit et al 1986;Matthews et al 1999;Paganini-Hill and Henderson 1994;Tang et al 1996;Yaffe et al 1998;Zandi et al 2002). However, the therapeutic potential of hormone-based therapies for cognitive function/ AD is under scrutiny given that reports from the Women's Health Initiative Memory Study (WHIMS), demonstrated that women administered E 2 , alone or in combination with progestogens, had greater cognitive impairment, and AD risk increased twofold, compared to the placebo group (Shumaker et al 2003(Shumaker et al , 2004.…”

Section: Discussionmentioning

confidence: 99%

Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Frye

Walf

2009

AGE

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Although anxiety and depression are not the core symptoms of Alzheimer's Disease (AD), there are changes observed in mood in those with AD, as well as in the aging population. Anxiety and depression may be influenced by progesterone P 4 and/or its neuroactive metabolites, dihydroprogesterone (DHP) and 5α-pregnan-3α-ol-20-one (3α,5α-THP). To begin to investigate progestogens' role in AD, a double transgenic mouse model of early-onset familial AD that cooverexpresses mutant forms of amyloid precursor protein (APPswe) and presenilin 1 Δ exon 9 mutation was utilized. As such, the effects of long-term (from 6 to 12 months of age) administration of P 4 to ovariectomized (ovx) wildtype and APPswe+PSEN1Δe9 mice for changes in affective behavior was investigated. APPswe+PSEN1Δ9 mutant mice had increased anxiety-like (i.e., increased emergence latencies, decreased time spent on the open quadrants of the elevated zero maze) and increased depressive-like behavior (i.e., increased time spent immobile) than did wildtype mice. Compared to vehicle-administration, P 4 administration (which produced physiological circulating P 4 , DHP, and 3α,5α-THP levels, particularly in the wildtype mice) decreased depressant-like behavior in the forced swim test. These effects occurred independent of changes in general motor behavior/coordination, pain threshold, and plasma corticosterone levels. Thus, the APPswe+PSEN1Δ9 mutation alters affective behavior, and P 4 treatment reversed depressive-like behavior.

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Section: Discussionmentioning

confidence: 99%

Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Frye

Walf

2009

AGE

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“…With respect to the nervous system, many studies have suggested that ERT may improve cognitive functions, may protect against age-associated memory decline and may delay the onset and decrease the risk of AD (Phillips and Sherwin, 1992;Brenner et al, 1994;Henderson, 1994, 1996;Kawas et al, 1997;Jacobs et al, 1998;Resnick et al, 1998;Costa et al, 1999;Smith et al, 2001;Fillenbaum et al, 2001;Tang et al, 1996;Yaffe et al, 1998b). Estrogens may not only protect against the onset of AD, they may also maintain cognitive functions in women who already have AD Asthana et al, 1999Asthana et al, , 2001.…”

Section: Hormone Replacement Therapy In Humansmentioning

confidence: 99%

“…Estrogens may not only protect against the onset of AD, they may also maintain cognitive functions in women who already have AD Asthana et al, 1999Asthana et al, , 2001. However, some studies have questioned the positive impact of ERT on the risk of AD or on cognitive decline in women with AD (Brenner et al, 1994;Henderson et al, 2000;Mulnard et al, 2000;Wang et al, 2000).…”

Section: Hormone Replacement Therapy In Humansmentioning

confidence: 99%

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Schumacher

Weill-Engerer

Lière

et al. 2003

Progress in Neurobiology

272

171

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Without medical progress, dementing diseases such as Alzheimer's disease will become one of the main causes of disability. Preventing or delaying them has thus become a real challenge for biomedical research. Steroids offer interesting therapeutical opportunities for promoting successful aging because of their pleiotropic effects in the nervous system: they regulate main neurotransmitter systems, promote the viability of neurons, play an important role in myelination and influence cognitive processes, in particular learning and memory. Preclinical research has provided evidence that the normally aging nervous system maintains some capacity for regeneration and that age-dependent changes in the nervous system and cognitive dysfunctions can be reversed to some extent by the administration of steroids. The aging nervous system also remains sensitive to the neuroprotective effects of steroids. In contrast to the large number of studies documenting beneficial effects of steroids on the nervous system in young and aged animals, the results from hormone replacement studies in the elderly are so far not conclusive. There is also little information concerning changes of steroid levels in the aging human brain. As steroids present in nervous tissues originate from the endocrine glands (steroid hormones) and from local synthesis (neurosteroids), changes in blood levels of steroids with age do not necessarily reflect changes in their brain levels. There is indeed strong evidence that neurosteroids are also synthesized in human brain and peripheral nerves. The development of a very sensitive and precise method for the analysis of steroids by gas chromatography/mass spectrometry (GC/MS) offers new possibilities for the study of neurosteroids. The concentrations of a range of neurosteroids have recently been measured in various brain regions of aged Alzheimer's disease patients and aged non-demented controls by GC/MS, providing reference values. In Alzheimer's patients, there was a general trend toward lower levels of neurosteroids in different brain regions, and neurosteroid levels were negatively correlated with two biochemical markers of Alzheimer's disease, the phosphorylated tau protein and the ␤-amyloid peptides. The metabolism of dehydroepiandrosterone has also been analyzed for the first time in the aging brain from Alzheimer patients and non-demented controls. The conversion of dehydroepiandrosterone to 5-androstene-3␤,17␤-diol and to 7␣-OH-dehydroepiandrosterone occurred in frontal cortex, hippocampus, amygdala, cerebellum and striatum of both Alzheimer's patients and controls. The formation of these metabolites within distinct brain regions negatively correlated with the density of ␤-amyloid deposits.

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“…vitamin B 12 deficiency, alcohol abuse), can be reasonably expected to reduce the incidence of subsequent dementia. While there is evidence from case control and cohort studies that postmenopausal hormone replacement therapy may reduce the incidence of AD, 62 a recent RCT of estrogen replacement in established AD failed to demonstrate cognitive improvement or slowing of the dementing process. 63 Therefore, it is premature to recommend estrogens solely for the purpose of preventing AD.…”

Section: Prevention Of Dementiamentioning

confidence: 99%

The Recognition, Assessment and Management of Dementing Disorders: Conclusions from the Canadian Consensus Conference on Dementia

Patterson

Grek

Gauthier

et al. 2001

Can. J. Neurol. Sci.

122

119

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To develop evidence based consensus statements on which to build clinical practice guidelines for primary care physicians towards the recognition, assessment and management of dementing disorders; ii) to disseminate and evaluate the impact of these statements and guidelines built on these statements. O p t i o n s : Structured approach to assessment, including recommended laboratory tests, choices for neuroimaging and referral; management of complications (especially behaviour problems and depression) and use of cognitive enhancing agents. Potential outcomes: Consistent and improved clinical care of persons with dementia; cost containment by more selective use of laboratory investigations, neuroimaging and referrals; appropriate use of cognitive enhancing agents. E v i d e n c e : Authors of each background paper were entrusted to: perform a literature search, discover additional relevant material including references cited in retrieved articles; consult with other experts in the field and then synthesize information. Standard rules of evidence were applied. Based upon this evidence, consensus statements were developed by a group of experts, guided by a steering committee of eight individuals from the areas of Neurology, Geriatric Medicine, Psychiatry, Family Développer des énoncés consensuels basés sur les données actuelles de la science sur lesquels on puisse construire des lignes directrices cliniques pour les médecins de première ligne pour l'identification, l'évaluation et la prise en charge des patients déments; ii) diffuser et évaluer l'impact de ces énoncés et des lignes directrices basées sur ces énoncés. O p t i o n s : Une approche structurée pour l'évaluation, incluant les épreuves de laboratoire recommandées, les choix d'examens de neuroimagerie et de référence en spécialité; la prise en charge des complications (spécialement des problèmes de comportement et de dépression) et l'utilisation d'agents qui améliorent la fonction cognitive. Bénéfices potentiels: Des soins améliorés et fiables aux personnes démentes; un contrôle des coûts par une utilisation plus judicieuse des examens de laboratoire, de la neuroimagerie et de la référence en spécialité; une utilisation appropriée des agents qui améliorent la fonction cognitive. É v i d e n c e : Les auteurs de chaque article de fond ont reçu le mandat de faire une recherche de la littérature pour ajouter des informations pertinentes incluant les références citées dans ces articles; consulter d'autres experts dans ce domaine et faire une synthèse de l'information. Ces tâches ont été effectuées conformément aux normes de la preuve. Sur la foi de cette évidence, les énoncés consensuels ont été développés par un groupe d'experts, guidé par un comité de direction de huit individus des domaines de la neurologie, de la gériatrie, de la psychiatrie, de la médecine familiale, de la médecine préventive et des systèmes de santé. Va l e u r s : Des recommandations ont été développées en portant une attention particulière sur le contexte des soins de première ligne ...

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Postmenopausal Estrogen Replacement Therapy and the Risk of Alzheimer's Disease: A Population-based Case-Control Study

Cited by 275 publications

References 0 publications

Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

The Recognition, Assessment and Management of Dementing Disorders: Conclusions from the Canadian Consensus Conference on Dementia

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