Prevalence of low bone density in women with developmental disabilities.

This study was designed to assess the prevalence and severity of low bone mineral density in an institutionalized population of postmenopausal women (n = 79) with developmental disabilities, using quantitative ultrasound of the calcaneus. The results demonstrate that this population has a significantly lower quantitative ultrasound index (QUI) of the calcaneus compared with a referent population of age-matched control subjects without mental disabilities. We used the QUI T-score threshold of <-2.0 standard deviations (SDs) to define individuals at high risk for osteoporosis, and 82% of the study participants met this criterion. Furthermore, approx 43% of the population had a heel QUI that was more than 2 SDs below that of age-matched control subjects, consistent with a severe degree of demineralization.

The effects of metrifonate on the cognitive, behavioral, and functional performance of Alzheimer's disease patients. Metrifonate Study Group.

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of metrifonate, a long-acting acetylcholinesterase inhibitor, in patients clinically diagnosed with probable Alzheimer's disease of mild-to-moderate severity. METHOD: This was a prospective, multicenter, 26-week, double-blind, parallel group study. The 264 randomized patients met diagnostic criteria of the National Institute of Neurological and Communicative Diseases and Stroke and the Alzheimer's Disease and Related Disorders Association for probable Alzheimer's disease. Patients had Mini-Mental State Examination (MMSE) scores of 10-26 and ischemic scores (Rosen modification) of <4. Metrifonate-treated patients received a single 50-mg dose once daily. The efficacy of metrifonate was investigated with respect to 3 symptom domains. Cognitive performance was analyzed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the MMSE. Psychiatric and behavioral disturbances were analyzed using the Neuropsychiatric Inventory (NPI) and the ADAS-Noncognitive subscale (ADAS-Noncog). The ability to perform instrumental and basic activities of daily living was evaluated using the Disability Assessment for Dementia (DAD) scale. Additionally, global state was assessed using the Clinician Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus) scale. RESULTS: After 26 weeks of metrifonate therapy, a statistically significant benefit of metrifonate was observed in the cognitive performance of Alzheimer's disease patients (ADAS-Cog, t = 2.55, df = 237, p = .012; MMSE, t = 4.60, df = 237, p = .0001). Metrifonate also significantly attenuated the deterioration in activities of daily living of the patients (DAD total score, t = -2.11, df = 233, p = .036) and relieved patients' psychiatric and behavioral disturbances (NPI total score, t = 2.51, df = 233, p = .013). In addition, metrifonate significantly improved the scores for the global state of the patients (CIBIC-Plus, t = 2.07, df = 232, p = .039). Metrifonate was well tolerated; adverse events were predominantly mild in intensity, and no hepatotoxicity was observed. CONCLUSION: In this study, metrifonate was safe and well tolerated. It benefited the cognitive decline, psychiatric and behavioral disturbances, impaired ability to perform instrumental and basic activities of daily living, and global state of patients diagnosed with mild-to-moderate Alzheimer's disease.

Self-esteem and neuroendocrine response to challenge: MacArthur studies of successful aging.

The role of self-esteem in modulating patterns of neuroendocrine response to challenge at older ages was examined in 16 healthy 70-yr-olds. Responses to two challenges were examined: (1) a driving simulation designed to reflect a 'real life' challenge situation; and (2) a pharmacologic, corticotropin-releasing-hormone (CRH) challenge (1 micrograms/kg). Both challenges evoked significant elevations in cortisol and adrenocorticotropic hormone (ACTH). Levels of self-esteem were significantly and negatively associated with peak elevations in cortisol in response to the driving simulation challenge (r = -0.51, p = 0.04). ACTH responses showed similar trends (r = -0.41, p = 0.12). Self-esteem levels were not correlated with responses to the CRH challenge. These data indicate that psychological characteristics such as self-esteem may play a role in modulating patterns of neuroendocrine response to cognitive/behavioral challenges in everyday life in older individuals.

Cytoarchitectural relationships between [3H]ouabain binding and mRNA for isoforms of the sodium pump catalytic subunit in rat brain.

We examined the cell type-specific expression of the alpha 1, alpha 2, and alpha 3 subunits of the sodium pump in rat brain using in situ hybridization and [3H]ouabain autoradiography. These techniques allowed us to colocalize mRNA and functional alpha 2/alpha 3 pumps on adjacent sections. The perikarya of many neurons possessed high levels of alpha 1 and/or alpha 3 transcripts, while alpha 2 mRNA appeared to be present in only a few neuronal types. [3H]Ouabain binding in general paralleled the distribution of alpha 3 mRNA-positive neurons. The regional variation of alpha 1 and alpha 3 transcripts was complex and varied. Large neurons of the olfactory bulb and piriform cortex expressed high levels of alpha 3 transcripts, but low levels of alpha 1 mRNA. In frontal cortex, neurons of layers II-III were enriched in alpha 1 mRNA, while those in layer V exhibited high levels of alpha 3 transcripts. In the hippocampus, principal neurons expressed all three alpha subunit mRNAs. CA subfield pyramidal neurons exhibited a high alpha 3/alpha 1 ratio, while dentate granule cells and hilar pyramidal neurons expressed approximately equal levels of alpha 1 and alpha 3. In the cerebellum, Purkinje and Golgi cells were rich in alpha 3 mRNA, while the granule cells appeared to express only alpha 1 transcripts. The distribution of functional sodium pump protein, as localized by [3H]ouabain binding, was highest in the neuropil of the hippocampus and cerebral cortex, and lowest over perikarya and white matter. [3H]ouabain did not bind to alpha 1 pump units, as confirmed by the complete absence of labeling over the choroid plexus, a tissue expressing only alpha 1 mRNA. In the cerebellum, regions of dense [3H]ouabain binding were localized to the granule cell layer, the inner third of the molecular layer in the basket region, and the deep cerebellar nuclei. Surprisingly, the dense neuropil in the outer 2/3 of the molecular layer lacked high [3H]ouabain binding. Thus, functional alpha 3 sodium pump units appear distributed to the axon terminals and not to apical dendrites of Purkinje, Golgi and basket cells. A similar pattern of increased [3H]ouabain binding in axonal but not dendritic fields of alpha 3-enriched neurons was present in the cerebral cortex and the hippocampus. Considering that many alpha 3-enriched neurons are of the Golgi I type with long axons, the alpha 3 isoform may be preferentially directed into axons to function in presynaptic membranes.