94290406 Estrogen replacement therapy in older women: Comparisons between Alzheimer's disease cases and nondemented control subjects

Vw, Henderson; Paganini-Hill, A.; Emanuel, Christina K.; Dunn, Meleana; Buckwalter, J. Galen

doi:10.1016/0378-5122(95)98231-i

Cited by 135 publications

(172 citation statements)

References 0 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…In general, these effects are seen within a number of weeks and are reversible. Another aspect of estrogen action in the aging brain is that estrogen treatment of postmenopausal women appears to have a protective effect on the brain re Alzheimer's disease (12,50,51,62,108,140). It is likely that these protective actions involve a number of other actions of estrogens besides inducing synapses.…”

Section: Importance Of Sex Differences and Sex Hormonesmentioning

confidence: 99%

Stress and the Aging Hippocampus

McEwen

1999

Frontiers in Neuroendocrinology

208

View full text Add to dashboard Cite

The ''glucocorticoid cascade hypothesis'' of hippocampal aging has stimulated a great deal of research into the neuroendocrine aspects of aging and the role of glucocorticoids, in particular. Besides strengthening the methods for investigating the aging brain, this research has revealed that the interactions between glucocorticoids and hippocampal neurons are far more complicated than originally envisioned and involve the participation of neurotransmitter systems, particularly the excitatory amino acids, as well as calcium ions and neurotrophins. New information has provided insights into the role of early experience in determining individual differences in brain and body aging by setting the reactivity of the hypothalamopituitary-adrenal axis and the autonomic nervous system. As a result of this research and advances in neuroscience and the study of aging, we now have a far more sophisticated view of the interactions among genes, early development, and environmental influences, as well as a greater appreciation of events at the cellular and molecular levels which protect neurons, and a greater appreciation of pathways of neuronal damage and destruction. While documenting the ultimate vulnerability of the brain to stressful challenges and to the aging process, the net result of this research has highlighted the resilience of the brain and offered new hope for treatment strategies for promoting the health of the aging brain. KEY WORDS: stress; hippocampal aging; glucocorticoid cascade hypothesis. 1999 Academic Press INTRODUCTIONThe hippocampus is a particularly vulnerable and sensitive region of the brain that is also very important for declarative and spatial learning and memory (36). Hippocampal neurons are vulnerable to seizures, strokes, and head trauma, as well as responding to stressful experiences (27,92,130). At the same time they show remarkable plasticity, involving long-term synaptic potentiation and depression, dendritic remodeling, synaptic turnover, and neurogenesis in the case of the dentate gyrus (Fig 1) (17,27,92).The work of aus der Muhlen and Ockenfels (3) first drew attention to potentially toxic actions of adrenal steroids. The reported darkly stained neurons in the hippocampus of guinea pigs exposed to high levels of glucocorticoids, an observation that has been confirmed and extended to repeated stress in subsequent studies (41,100), although there are still some doubts as to whether ''dark neurons'' may be artifacts of tissue trauma (18). In 1968, we discovered receptors for adrenal steroids in hippocampus (95), and it is now known that two types of adrenal steroid receptors exist in the hippocampus and other brain regions and mediate a variety of adrenal steroid effects on excitability, neurochemistry, and structure (27). Landfield (68) and then Sapolsky (127,128) provided evidence for a role of adrenal steroids in neuronal aging in the hippocampus, leading to the formulation of the ''glucocorticoid cascade hypothesis '' (130). This hypothesis states that glucocorticoids participate in a ...

show abstract

Section: Importance Of Sex Differences and Sex Hormonesmentioning

confidence: 99%

Stress and the Aging Hippocampus

McEwen

1999

Frontiers in Neuroendocrinology

208

View full text Add to dashboard Cite

show abstract

“…The abrupt loss of serum sex steroids with reproductive senescence not surprisingly correlates with an increased prevalence of cognitive disease in women (Brookmeyer et al, 1998;Jorm et al, 1987;McGonigal et al, 1993), while sex steroid replacement therapy decreases the incidence (Henderson et al, 1994) and delays the onset of cognitive decline in women and men (reviewed in Gleason et al, 2005). Interestingly, ALS is associated with the loss of cognitive-behavioral competency with progressive involvement of the prefrontal cortex and, in a few instances, profound dementia (Montgomery and Erickson, 1987), supportive of a hormonal component to the disease process.…”

Section: Genetic and Age-linked Alterations In Lactate Homeostasis Unmentioning

confidence: 99%

Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis

Meethal

Atwood

2012

Neurobiology of Aging

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease) is a progressive debilitating neurodegenerative disease with no cure. We propose a novel molecular model for the pathogenesis of ALS that involves an adenosine triphosphate (ATP)-dependent muscle neuronal lactate shuttle (MNLS) at the neuromuscular junction (NMJ) to regulate the flow of lactate from muscle to neurons and vice versa. Failure of the MNLS due to respiratory chain dysfunction is proposed to result in lactate toxicity and degeneration of nerve endings at the NMJ leading to nerve terminus dysjunction from the muscle cell. At a critical threshold where denervation outpaces reinnervation, a vicious cycle is established where the remaining innervated muscle fibers are required to work harder to compensate for normal function, and in so doing produce toxic lactate concentrations which induces further denervation and neuronal death. This mechanism explains the exponential progression of ALS leading to paralysis. The molecular events leading to the dysregulation of the MNLS and the dismantling of NMJ are explained in the context of known ALS familial mutations and age-related endocrine dyscrasia. Combination drug therapies that inhibit lactate accumulation at the NMJ, enhance respiratory chain function, and/or promote reinnervation are predicted to be effective therapeutic strategies for ALS. Published by Elsevier Inc.

show abstract

“…94 In case-control studies, with one exception, 95 a number of different lines of evidence consistently point to beneficial effects of estrogen on cognitive function in women. [96][97][98][99] In most of these studies, the odds ratios for developing AD have been calculated for subjects who are taking or not taking ERT, based on retrospectively or prospectively acquired information and reductions in the 50% range have been reported. [96][97][98][99] However, a recent meta-analysis of ten studies of postmenopausal ERT involving over 3,000 women (including cross-sectional, case control and clinical trials), concluded that the relative risk of developing AD after exposure to estrogen was .71 (95% CI .53-.96).…”

Section: Estrogen Replacement Therapy (Ert)mentioning

confidence: 99%

Preventing Dementia

Black

Patterson

Feightner

2001

Can. J. Neurol. Sci.

View full text Add to dashboard Cite

Suppl. 1 -S56The concept of primary prevention of dementia is relatively new but will assume increasing importance as dementia prevalence increases in our graying population 1 and as the etiological factors and molecular pathogenetic mechanisms of primary degenerative dementias become better understood. 2Current definitions of dementia require memory impairment and cognitive dysfunction in at least one other domain of sufficient degree to interfere with social functioning.3 In this review we emphasize prevention of dementia in individuals who are cognitively normal but may be at risk for dementia, or who are cognitively impaired but not yet demented. Potential preventative measures include avoidance or control of modifiable risk factors to prevent progression to clinically manifest dementia. Secondary prevention of the degenerative dementias is equivalent to treatment, which is discussed in a companion article in this series. Recent clinical trials have provided evidence for modest symptomatic stabilization with socalled cognitive enhancing agents. If effective retardive therapies or neuroregenerative strategies are developed, in the future it may be possible to delay progression or even partially reverse dementing illness.ABSTRACT: Primary prevention will become increasingly important as dementia prevalence increases and effective retardive therapies are developed. To date, only one randomized controlled trial (involving treatment of systolic hypertension) has demonstrated that the incidence of dementia can be reduced. Physicians should remain alert to possible secondary causes of dementia and correct these whenever possible. Primary and secondary prevention of stroke should reduce dementia related to cerebrovascular disease either directly or as a comorbid factor in Alzheimer's disease (AD). Epidemiological studies have revealed a number of risk factors for AD including genetic mutation, susceptibility genes, positive family history, Down's syndrome, age, sex, years of education, head trauma and neurotoxins. In casecontrol studies non-steroidal anti-inflammatory medication and estrogen replacement therapy appear to decrease the relative risk of developing AD. Further research to develop and test preventative therapies in AD and other dementias should be strongly encouraged.RÉSUMÉ: Prévention de la démence. La prévention primaire va devenir de plus en plus importante à mesure que la prévalence de la démence augmente et que des stratégies efficaces pour en retarder l'apparition sont développées. Pour l'instant, une seule étude randomisée contrôlée (traitement de l'hypertension systolique) a démontré que l'incidence de la démence peut être réduite. Les médecins devraient demeurer vigilants pour détecter la présence causes secondaires de démence et les corriger si possible. La prévention primaire et secondaire de l'accident vasculaire cérébral devrait diminuer l'incidence de la démence reliée à la maladie cérébrovasculaire, soit directement ou comme facteur de comorbidité dans la maladie d'Alzheimer (MA). Des étud...

show abstract

94290406 Estrogen replacement therapy in older women: Comparisons between Alzheimer's disease cases and nondemented control subjects

Cited by 135 publications

References 0 publications

Stress and the Aging Hippocampus

Stress and the Aging Hippocampus

Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis

Preventing Dementia

Contact Info

Product

Resources

About