It is unclear whether persons with diabetes are at increased risk for dementia, including Alzheimer's disease. Existing studies are limited by small sample size, selection bias, and case-control designs. This population-based historical cohort study provides estimates of the risk of dementia and Alzheimer's disease associated with adult onset diabetes mellitus (AODM). The sample included all persons with AODM residing in Rochester, Minnesota, on January 1, 1970, plus all persons diagnosed in Rochester or who moved to Rochester with the diagnosis between January 1, 1970, and December 31, 1984. Individuals were followed through review of their complete medical records from AODM diagnosis until dementia onset, emigration, death, or January 1, 1985. Standardized morbidity ratios for dementia and Alzheimer's disease were calculated, using an expected incidence based on age- and sex-specific rates for the Rochester population. Poisson regression was used to estimate risks for persons with AODM relative to those without. Of the 1,455 cases of AODM followed for 9,981 person-years, 101 developed dementia, including 77 who met criteria for Alzheimer's disease. Persons with AODM exhibited significantly increased risk of all dementia (Poisson regression relative risk (RR) = 1.66, 95% confidence interval (CI) 1.34-2.05). Risk of Alzheimer's disease was also elevated (for men, R = 2.27, 95% CI 1.55-3.31; for women, RR = 1.37, 95% CI 0.94-2.01). These findings emphasize the importance of AODM prevention and prompt additional investigation of the relation between AODM and dementia.

Our study suggests that slow gait precedes cognitive decline. Gait speed may be useful as a reliable, easily attainable, and noninvasive risk factor for cognitive decline.

Objective-To assess the feasibility of using magnetic resonance imaging (MRI) measurements as a surrogate end point for disease progression in a therapeutic trial for Alzheimer's disease (AD).Methods-Three-hundred-sixty-two patients with probable AD from 38 different centers participated in the MRI portion of a 52 week randomized placebo controlled trial of milameline, a muscarinic receptor agonist. The therapeutic trial itself was not completed due to projected lack of efficacy on interim analysis; however, the MRI arm of the study was continued. Of the 362 subjects who underwent a baseline MRI study, 192 subjects underwent a second MRI one-year later. Hippocampal volume and temporal horn volume were measured from the MRI scans.Results-The annualized percent change in hippocampal volume (−4.9%) and temporal horn volume (16.1%) in the study patients were consistent with data from prior single site studies. Correlations between the rate of MRI volumetric change and change in behavioral/cognitive measures were greater for the temporal horn than for the hippocampus. Decline over time was more consistently seen with imaging measures, 99% of the time for the hippocampus, than behavioral/ cognitive measures (p<0.001). Greater consistency in MRI than behavioral/clinical measures resulted in markedly lower estimated sample size requirements for clinical trials. The estimated number of subjects per arm required to detect a 50% reduction in the rate of decline over one year are: ADASCog 320; MMSE 241; hippocampal volume 21; temporal horn volume fifty-four. Conclusion-The consistency of MRI measurements obtained across sites, and the consistency between the multi-site milameline data and that obtained in prior single site studies, demonstrate the technical feasibility of using structural MRI measures as a surrogate end point of disease progression in therapeutic trials. However, validation of imaging as a biomarker of therapeutic efficacy in AD still awaits a positive trial.The primary outcome measurements for therapeutic trials in Alzheimer's disease (AD) patients are behavioral or cognitive. Due to the inherent test-retest variability in such measurements however, alternatives have been sought. Magnetic resonance imaging (MRI) measurements of rates of whole brain or hippocampal atrophy have been, and are currently being used as outcome measures in several therapeutic trials for AD. Although imaging has been used in clinical trials on AD and vascular disease for diagnostic purposes, to our knowledge, no publication has appeared describing the MRI results of a therapeutic trial in which structural MRI was used as NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript an outcome measure. MRI measures were added to this trial to gain a claim for effects on disease progression as opposed to just symptomatic treatment in those instances where treatment effect was shown on the behavioral/cognitive measures 1-7 .We report the MRI results of a therapeutic trial of milameline, a centrally active muscari...

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We report a sensing methodology that combines magnetic separation (MS) and magnetic relaxation switching (MS-MRS) for one-step detection of bacteria and viruses with high sensitivity and reproducibility. We first employ a magnetic field of 0.01 T to separate the magnetic beads of large size (250 nm in diameter) from those of small size (30 nm in diameter) and use the transverse relaxation time (T2) of the water molecules around the 30 nm magnetic beads (MB30) as the signal readout of the immunoassay. An MS-MRS sensor integrates target enrichment, extraction, and detection into one step, and the entire immunoassay can be completed within 30 min. Compared with a traditional MRS sensor, an MS-MRS sensor shows enhanced sensitivity, better reproducibility, and convenient operation, thus providing a promising platform for point-of-care testing.