Goal-directed treatment of osteoporosis.

Drug treatment for osteoporosis typically begins with an oral bisphosphonate, regardless of initial bone mineral density (BMD) or fracture risk, and decisions to continue or change treatment are often based on evidence of response to treatment based on changes in BMD, bone turnover markers, and occurrence of fractures. This pattern differs from preventive therapy for other conditions, such as hypertension, where treatment is based on achieving a goal. We propose that a goal be established to guide treatments to reduce fracture risk. The goal could be a certain risk of fracture or level of BMD. Goal-directed treatment would individualize the initial choice of treatment based on the probability that alternatives would achieve the patient's goal. In contrast to changing treatments based on years of use or failure to respond, the patient's BMD and risk would be reassessed periodically and decisions to stop or change treatment would be based on achieving or maximizing the chance of reaching an acceptable level of fracture risk or BMD. The acceptance of goal-directed treatment and application to practice will require a consensus on a number of issues about goals along with models of fracture risk while on treatment and probabilities of achieving goals. The result could be more rational and effective use of the expanding array of treatments for osteoporosis.

New acetylcholinesterase inhibitors for Alzheimer's disease.

Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in Alzheimer's disease (AD) because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia gravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEI) continue to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs in development and their respective mechanisms of actions. This pharmacological approach continues to be active with many promising compounds.

The nicotinic acetylcholine receptor: smoking and Alzheimer's disease revisited.

Epidemiological studies regarding Alzheimer's disease (AD) in smokers currently suggest inconsistent results. The clinicopathological findings also vary as to how AD pathology is affected by smoking behavior. Even though clinicopathological, functional, and epidemiological studies in humans do not present a consistent picture, much of the in vitro data implies that nicotine has neuroprotective effects when used in neurodegenerative disorder models. Current studies of the effects of nicotine and nicotinic agonists on cognitive function in both the non-demented and those with AD are not convincing. More data is needed to determine whether repetitive activation of nAChR with intermittent or acute exposure to nicotine, acute activation of nAChR, or long-lasting inactivation of nAChR secondary to chronic nicotine exposure will have a therapeutic effect and/or explain the beneficial effects of those types of drugs. Other studies show multifaceted connections between nicotine, nicotinic agonists, smoking, and nAChRs implicated in AD etiology. Although many controversies still exist, ongoing studies are revealing how nicotinic receptor changes and functions may be significant to the neurochemical, pathological, and clinical changes that appear in AD.

Depressive symptoms in late life: associations with apathy, resilience and disability vary between young-old and old-old.

OBJECTIVE: Prior research has found that disability and apathy are associated with late-life depression. However, the effect of age on these associations in "late-life," an ambiguous term encompassing all individuals typically older than 60 years, has not been examined. We investigated the association of depression with disability, apathy and resilience across the age range of late-life. METHODS: One hundred and five community-dwelling elderly with moderate levels of disability were assessed using the Geriatric Depression Scale (GDS), Hardy-Gill Resilience Scale, Starkstein Apathy Scale and IADL/ADL questionnaire. Multiple regression analysis was used to assess relationships between depression, disability, apathy and resilience, stratified by age (<80 vs. >80). RESULTS: In the <80 year old subject group, resilience, apathy and disability scores (partial type III R(2) = 11.1%, 10.4% and 12.8%, respectively) equally contributed to the variability of GDS score. In contrast, in the >80 year old subject group, apathy (partial type III R(2) = 18.7%) had the greatest contribution to GDS score. CONCLUSIONS: In elderly persons under age 80, resilience, apathy and disability all have relatively equal contributions to depression scores, whereas in those over age 80, depression is most highly correlated with apathy. These data suggest that depressive symptoms in elderly persons have different clinical features along the age spectrum from young-old to old-old.

Neuropsychological performance in pediatric bipolar disorder.

BACKGROUND: Growing awareness of childhood bipolar disorder necessitates further cognitive neuroscience research to determine unique developmental differences between pediatric and adult onset bipolar disorder. We sought to examine whether neuropsychological function in children with bipolar disorder resembles that in adults with the illness and to extend our knowledge about cognitive function in pediatric bipolar disorder. METHODS: We administered a computerized neuropsychological test battery known as the Cambridge Neuropsychological Test Automated Battery to a sample of 21 children and adolescents with bipolar disorder and compared them with 21 age- and gender-matched controls. RESULTS: In comparison to controls, children with bipolar disorder were impaired on measures of attentional set-shifting and visuospatial memory. Post hoc analyses in pediatric bipolar disorder subjects did not show significant associations between neuropsychological performance and manic symptomatology or attention-deficit/hyperactivity disorder comorbidity. CONCLUSIONS: Cambridge Neuropsychological Test Automated Battery data presented here in pediatric bipolar disorder fit well within the broader framework of known neurocognitive deficits in adult bipolar disorder. Our pediatric bipolar disorder subjects demonstrated selective deficiencies in attentional set-shifting and visuospatial memory. Our work suggests altered ventrolateral prefrontal cortex function, especially when linked to other lesion and neuroimaging studies.

Pertussis in Louisiana.

Analysis of the surveillance data from the Louisiana Office of Public Health showed a progressive decline of pertussis in Louisiana. Louisiana rates are lower than those of the United States, and increased rates observed among adults in other states are not observed in Louisiana. This would likely be due a lack of suspicion for pertussis in adults and a resultant lack of diagnosis and reporting. Two recent outbreak investigations in a health facility are summarily described, showing that pertussis is still a major cause of concern for the healthcare community.

West nile epidemic in louisiana in 2002.

In 2002, 329 cases of West Nile illness were reported in Louisiana, including 204 cases of West Nile meningoencephalitis and 125 cases of West Nile fever. Clinical presentation of meningoencephalitis or of West Nile fever was confirmed serologically. There were 24 deaths. Age group distribution showed predominance among persons aged 45 years or older. The epidemic curve, based on date of diagnosis, showed numerous foci progressing in successive waves. The first cases occurred in mid-June. A peak was reached by the first week of August, after which the epidemic progressively subsided.