ABSTRACT
After advanced age, female sex is the major risk factor for late-onset Alzheimer's disease (AD), the most common cause of dementia affecting over 24 million people worldwide. The prevalence of AD is higher in women than in men, with postmenopausal women accounting for over 60% of all those affected. While most research has focused on gender-combined risk, emerging data indicate sex and gender differences in AD pathophysiology, onset, and progression, which may help account for the higher prevalence in women. Notably, AD-related brain changes develop during a 10-20 year prodromal phase originating in midlife, thus proximate with the hormonal transitions of endocrine aging characteristic of the menopause transition in women. Preclinical evidence for neuroprotective effects of gonadal sex steroid hormones, especially 17ß-estradiol, strongly argue for associations between female fertility, reproductive history, and AD risk. The level of gonadal hormones to which the female brain is exposed changes considerably across the lifespan, with relevance to AD risk. However, the neurobiological consequences of hormonal fluctuations, as well as that of hormone therapies, are yet to be fully understood. Epidemiological studies have yielded contrasting results of protective, deleterious and null effects of estrogen exposure on dementia risk. In contrast, brain imaging studies provide encouraging evidence for positive associations between greater cumulative lifetime estrogen exposure and lower AD risk in women, whereas estrogen deprivation is associated with negative consequences on brain structure, function, and biochemistry. Herein, we review the existing literature and evaluate the strength of observed associations between female-specific reproductive health factors and AD risk in women, with a focus on the role of endogenous and exogenous estrogen exposures as a key underlying mechanism. Chief among these variables are reproductive lifespan, menopause status, type of menopause (spontaneous vs. induced), number of pregnancies, and exposure to hormonal therapy, including hormonal contraceptives, hormonal therapy for menopause, and anti-estrogen treatment. As aging is the greatest risk factor for AD followed by female sex, understanding sex-specific biological pathways through which reproductive history modulates brain aging is crucial to inform preventative and therapeutic strategies for AD.
ABSTRACT
Irrigated agriculture has expanded greatly in the water-rich U.S. northern lake states during the past half century. Source water there is usually obtained from glacial aquifers strongly connected to surface waters, so irrigation has a potential to locally decrease base flows in streams and water levels in aquifers, lakes, and wetlands. During the nascent phase of the irrigation expansion, water availability was explored in works of some fame in the Wisconsin central sands by Weeks et al. (1965) on the Little Plover River and Weeks and Stangland (1971) on "headwater area" streams and lakes. Four decades later, and after irrigation has grown to a dominant landscape presence, we revisited irrigation effects on central sands hydrology. Irrigation effects have been substantial, on average decreasing base flows by a third or more in many stream headwaters and diminishing water levels by more than a meter in places. This explains why some surface waters have become flow and stage impaired, sometimes to the point of drying, with attendant losses of aquatic ecosystems. Irrigation exerts its effects by increasing evapotranspiration by an estimated 45 to 142 mm/year compared with pre-irrigated land cover. We conclude that irrigation water availability in the northern lake states and other regions with strong groundwater-surface water connections is tied to concerns for surface water health, requiring a focus on managing the upper few meters of aquifers on which surface waters depend rather than the depletability of an aquifer.
