Clinical Aspects of Glucose Metabolism and Chronic Disease.

The burden of chronic disease is an emerging world health problem. Advances made in the treatment of individual disease states often fail to consider multimorbidity patterns in clinical research models. Adjusting for age as a confounder ignores its contribution as a powerful risk factor for most chronic diseases. Sarcopenia is an age-related loss of skeletal muscle mass, which is accelerated by chronic inflammation and its resulting cascade of cytokines. Skeletal muscle loss results in insulin resistance, hyperglycemia, and altered mitochondrial glucose signaling pathways. Vascular disease in the brain may alter blood-brain barrier function, allowing transport of substances into the brain which adversely affect the "astrocyte-centric" subunit. Neurogenesis that provides neuronal plasticity is impaired in the diabetic brain, while insulin resistance markers such as insulin-like growth factor (IGF-1) and insulin receptor substrate (IRS-1) are associated with poor cognitive performance. Advanced glycation end products generated by chronic hyperglycemia are found in postmortem AD brain. Intranasal insulin administration, a preferential route for CNS delivery, improved cognitive function in healthy adults, without affecting circulating levels of insulin or glucose. Exercise has demonstrated a neuroprotective effect through induction of antioxidative enzymes, neurotrophic, and vascular endothelial growth factors. Sarcopenia appears to be a dynamic process and is potentially reversible with attention to nutrition and cardiovascular fitness. Early detection and intervention may slow the progression of multimortality disease states and should be a focus of worldwide health systems.

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like PET scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like positron emission tomography (PET) scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

Diazepam and discriminative motor control: acute, chronic and withdrawal effects.

Rats were trained to hold a force transducer operated with a paw so that it remained between upper and lower limits of a force band for a continuous 1.5-sec period to deliver each food pellet. Acute doses of diazepam impaired measures of this performance. Separate groups received chronic diazepam injections (6 mg/kg, IP) either presession (Before Group) or postsession (After Group), or presession vehicle (Vehicle Group). The After and Vehicle Groups demonstrated that neither chronic postsession diazepam, nor time alone, altered motor performance. The performance of the Before Group was affected by the daily diazepam, and although tolerance to the impairment developed, it was incomplete. Late in the chronic-administration phase (after 75 days) a toxic effect of the suspending agent became evident in all groups as a decrease in work rate, although the other performance indices were not affected. The withdrawal of diazepam from the Before Group led to improved performance which returned to the original baseline level.