Estrogen replacement therapy for the potential treatment or prevention of Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that occurs gradually and results in memory loss, behavior and personality changes, and a decline in cognitive abilities. Although basic biological data suggest that estrogen may have neuroprotective and neuroenhancing functions, a number of studies have produced conflicting findings on the use of estrogen for maintaining cognitive function in older people. This review summarizes clinical studies that have examined the effects of estrogen in women with AD.

Incidence and remission of insomnia among elderly adults in a biracial cohort.

OBJECTIVES: To determine the incidence and remission rates of insomnia in older adults according to race and associated risk factors in a three-year longitudinal study. METHODS: 2,971 men and women, aged 65 years and older, completed questionnaires administered by trained interviewers at baseline and three years later. Data concerning difficulty falling asleep or early morning arousal (insomnia), along with self-reports of physical disability, respiratory symptoms, depressive symptomatology, perceived health status, and use of prescribed sedative medication, were collected and analyzed. RESULTS: Overall, 15% of the participants without symptoms of insomnia at baseline reported chronic difficulty falling asleep or early morning arousal three years later in follow-up interviews. African-American women had a significantly (p < 0.01) higher incidence of insomnia (19%) compared with African-American men (12%) or with white men and women (both 14%). Men were more likely than women to no longer report symptoms at follow-up (64% vs 42%; p < 0.01). For both races, the presence of depressed mood was a risk factor for the incidence of insomnia, and the absence of depressed mood was a predictor of remission. CONCLUSIONS: Insomnia occurs more frequently in African-American women than in African-American men or than in white men or women. Regardless of race, women are less likely than men to resolve their insomnia. The high prevalence and incidence of morbidity in elderly African-American women may contribute to their high rate of insomnia.

Associations of symptoms of sleep apnea with cardiovascular disease, cognitive impairment, and mortality among older Japanese-American men.

OBJECTIVES: To examine the association between symptoms of sleep apnea and prevalent cardiovascular disease, cognitive impairment, and subsequent 3-year mortality. DESIGN: A longitudinal study. SETTING: Participants lived in the community on Oahu, Hawaii. PARTICIPANTS: A total of 2905 older Japanese-American men participating in the fourth examination of the Honolulu Heart Program cohort study from 1991-1993, which is the baseline for the Honolulu-Asia Aging Study of dementia. MEASUREMENTS: Self-reported snoring, daytime sleepiness, and breathing pauses; diagnosed cardiovascular disease and dementia; cognitive functioning and vital status approximately 3 years later. RESULTS: More than 12% of the participants reported that they often or always snored loudly, and 8% reported being sleepy most of the day. Fewer than 2% reported that they stop breathing when sleeping, and this was found more frequently among habitual snorers (7%, P < .001) and those sleepy during the day (5%, P < .001). The prevalence of habitual snoring declined in the older age groups, was higher among those with greater Body Mass Index scores, and was not associated with the reporting of daytime sleepiness, diagnosis of heart disease, stroke, dementia, or cognitive impairment. Daytime sleepiness was more prevalent at older ages and was associated with a higher prevalence of heart disease and with cognitive impairment and dementia, chronic obstructive pulmonary disease, and diabetes. Self-reported apnea was associated only with a history of pneumonia. Three-year mortality was not associated with these symptoms after adjusting for prevalent heart disease and cognitive impairment. CONCLUSION: Symptoms of sleep apnea are reported less frequently in older Japanese-American men. Excessive daytime sleepiness is associated with poor cognition and dementia, but whether it also is an indicator for sleep apnea in this age group remains unclear. Epidemiologic studies of sleep apnea in older adults will require polysomnography to determine accurately the correlates and consequences of this condition.

Sleep complaints among elderly persons: an epidemiologic study of three communities.

The frequencies of five common sleep complaints--trouble falling asleep, waking up, awaking too early, needing to nap and not feeling rested--were assessed in over 9,000 participants aged 65 years and older in the National Institute on Aging's multicentered study entitled "Established Populations for Epidemiologic Studies of the Elderly" (EPESE). Less than 20% of the participants in each community rarely or never had any complaints, whereas over half reported at least one of these complaints as occurring most of the time. Between 23% and 34% had symptoms of insomnia, and between 7% and 15% percent rarely or never felt rested after waking up in the morning. In multivariate analyses, sleep complaints were associated with an increasing number of respiratory symptoms, physical disabilities, nonprescription medications, depressive symptoms and poorer self-perceived health. Sleep disturbances, particularly among older persons, oftentimes may be secondary to coexisting diseases. Determining the prevalence of specific sleep disorders, independent of health status, will require the development of more sophisticated and objective measures of sleep disturbances.

Impairment in auditory and visual function follows perinatal viral infection in the rat.

Acoustic startle reflexes are elicited by intense tone bursts but inhibited if weak bursts precede reflex elicitation. Rats were infected by intracerebral inoculation with lymphocytic choriomeningitis virus (LCMV) at birth. Compared to control animals, infected animals had higher elicitation and inhibition thresholds and showed recruitment at intense stimulus levels. Histopathology revealed both cochlear and retinal degeneration. Like some infectious agents in humans, perinatal exposure to LCMV in the rat yields a severe polysensory neuropathy.

Congenital retinitis in the rat following maternal exposure to lymphocytic choriomeningitis virus.

A combined clinical and histopathological study of the eyes of the offspring of females inoculated with LCMV shows that about two-thirds of the pups develop some degree of retinal inflammation. This may range from a mild, subclinical reaction to an overt retinitis characterized clinically by demonstrable inflammatory and degenerative changes. Histopathologically, the latter condition presents the picture of an inflammatory reaction with extensive loss of photoreceptors and retinal neurons in general, macrophagic invasion, mild microcystoid degeneration and total or subtotal retinal detachment. This vertically-transmitted disease does not show the relentless progression and hemorrhagic tendency characteristic of the retinitis which occurs after direct viral inoculation. However, in the most severe cases the final outcome is the same, namely severe retinal impairment subsequent to widespread loss of photoreceptors. In the presence of consistently negative virological data, the hypothesis is proposed that this retinitis could be the result of a vertically-transmitted autoimmune disease.

Delayed-type hypersensitivity response in mice to Treponema pallidum.

C3H/HeJ mice which had been primed with either virulent or killed T. pallidum were studied for in vivo delayed-type hypersensitivity (DTH) responses to T. pallidum following local footpad challenge. Mice sustaining a chronic infection of 5 months duration failed to develop a DTH to treponemal antigens, whereas priming by a single intravenous injection with killed organisms resulted in a significant DTH response in mice when challenged 5 days later. Treatment of mice prior to priming with a single sublethal dose of cyclophosphamide (100 mg/kg body weight) not only failed to potentiate T. pallidum-DTH, but abrogated the response observed in untreated primed animals.

Chronic retinitis in rats infected as neonates with lymphocytic choriomeningitis virus: a clinical, histopathologic, and electroretinographic study.

The long-term sequelae to infection of neonatal rats with lymphocytic choriomeningitis virus were studied by a variety of approaches, including indirect ophthalmoscopic, electroretinographic, and histopathologic methods. Data from these studies demonstrated that a progressive chronic retinitis develops after the acute, virus-specific, immune-mediated retinopathy. This chronic inflammation eventually leads to a total destruction of the retinal architecture. An autoimmune reaction against normally sequestered retinal antigens, released during the acute state of necrotizing retinitis, is probably the initiating mechanism of the chronic disease. This experimental disease, triggered by infection with a relatively harmless virus, constitutes a very convenient animal model of chronic retinitis.

A Golgi analysis of cerebellar immunopathy in neonatal rats after infection with lymphocytic choriomeningitis virus.

Morphological changes in cerebellar neurons during the immune reaction to a viral infection were examined using Golgi methods. Wistar albino rats, infected at 4 days of age with lymphocytic choriomeningitis virus, were killed on postinfection days 4 to 10, and the cerebella were processed by rapid Golgi and Golgi-Cox methods. Some of the sections impregnated by the rapid Golgi method were subsequently processed for electron microscopy. Necrosis was evident in the lingula and portions of the posterior vermis by postinjection day 7. By the 9th day, degeneration was observed throughout the vermis. Purkinje cells appeared normal 4 days after infection, but by days 9 and 10, all the impregnated Purkinje cells had atrophic cell bodies; stunted, agglomerate dendrites; and dilated axons with collaterals that had many short processes. Some cells in the infected tissue did not resemble any normal cell type. These data indicate that the value of the Golgi method is a useful complement to conventional techniques for examining the neuropathological response to viral infections. In fact, it provides neuropathological information that is difficult or impossible to obtain with other procedures.

Circadian rhythm in pineal methionine S-adenosyltransferase.

The circadian rhythm of methionine S-adenosyltransferase, which catalyzes the formation of S-adenosylmethionine, a cosubstrate for melatonin in the pineal gland, follows the pattern of hydroxyindole-O-methyltransferase. Around the middle of the dark period, methionine S-adenosyltransferase and hydroxyindole-O-methyltransferase appear to be elevated by 2.5- and 1.5-fold, respectively, and tend to fall back during the light period.

Abrogation of genetically controlled resistance of mice to Treponema pallidum by irradiation.

Infection with Treponema pallidum, the causative agent of human syphilis, gives rise to a complex immune response involving both humoral and cellular components. The exact nature of this response and how it relates to the disease process is a matter of considerable speculation. In recent years, studies have been directed towards defining the role of cell-mediated immunity (CMI) in syphilis. These have been conducted mainly in vitro because the general unavailability of inbred rabbits, the principal animals for experimental syphilis research, has limited the application of in vivo procedures. A prime deterrent to using mice for the study of syphilis has been their failure to exhibit pathology, even in the face of a persistent infection. We report here that on intradermal (i.d.) infection, transient primary lesions, characteristic of those seen in naturally acquired human syphilis, can be produced regularly in some strains of mice but not others, indicating a genetic basis for host susceptibility. Strains of mice which normally fail to develop lesions, do so after exposure to ionising radiation. Evidence is presented for a multiple role of the immune response during local infection.

Failure to find H-2-associated susceptibility to LCM disease.

Nine strains of mice bearing five distinct H-2 genotypes were inoculated intracerebrally with LCMV. There was no association found between particular K or D allotypes and susceptibility to acute LCM disease.