RESULTS In 100 study participants, mean age 70.14 (SD 9.35) years, atropine-induced decrease in UPSIT score at baseline was not associated with change in ADAS-Cog or SRT scores over 52 weeks. Change in UPSIT score from 0 to 8 weeks did not show a significant association with change in the ADAS-Cog or SRT measures over 52 weeks. CONCLUSION These negative findings in a relatively large sample of patients with MCI did not replicate results in much smaller samples. Change in odor identification with anticholinergic challenge, and over 8 weeks, may not be useful predictors of cognitive improvement with CheI in patients with MCI.BACKGROUND Amnestic mild cognitive impairment (aMCI) is often the prodromal stage of Alzheimer's disease (AD). Although previous studies have suggested that computerized cognitive training is an effective non-pharmacological intervention for aMCI, large-sample, randomized controlled studies are warranted to provide a high level of evidence. OBJECTIVE To identify the efficacy of computerized cognitive training for aMCI.  https://www.selleckchem.com/products/apcin.html  METHODS This study will include 260 patients diagnosed with aMCI from 8 centers in China. A computerized multi-domain adaptive training program will be used in this study, and the targeted cognitive domains include memory, attention, language, and executive function. The patients will be randomized into either a cognitive-training group or an active-control group. The intervention is a 12-week internet-based cognitive training performed for 40 minutes per day, 4 days a week. Neuropsychological assessments and structural and functional MRI will be obtained at baseline, at the end of the intervention, and 6 months after randomization. The primary outcome will be the global cognitive function score assessed by Montreal Cognitive Assessment. The secondary outcomes include changes in other neuropsychological assessments and neuroplasticity changes measured by structural and functional MRI. RESULTS The trial is currently ongoing, and it is anticipated that recruitment will be completed in December 2020. CONCLUSION This multi-center, large-sample, randomized controlled trial will investigate the short and long-term effects of computerized cognitive training in patients with aMCI. Furthermore, the combination of functional and structural MRI results will also reveal the underlying mechanisms of the effect of intervention.BACKGROUND Emerging evidence suggests osteoarthritis (OA) and related symptom burden may increase risk for Alzheimer's disease and related dementias (ADRD). However, longitudinal studies are sparse, and none have examined the potential mediating effects of mood or sleep disorders. OBJECTIVE To determine the association of OA and related pain to incident ADRD in U.S. elders. METHODS In this retrospective cohort study, we used baseline and two-year follow-up data from linked Medicare claims and Medicare Current Beneficiary Survey files (11 pooled cohorts, 2001-2013). The study sample comprised 16,934 community-dwelling adults≥65 years, ADRD-free at baseline and enrolled in fee-for-service Medicare. Logistic regression was used to assess the association of OA and related pain (back, neck, joint, neuropathic) to incident ADRD, explore the mediating influence of mood and sleep disorders, and (sensitivity analyses) account for potential survival bias. RESULTS Overall, 25.5% of beneficiaries had OA at baseline (21.0% with OA and pain); 1149 elders (5.7%) were subsequently diagnosed with ADRD. Compared to beneficiaries without OA, those with OA were significantly more likely to receive a diagnosis of incident ADRD after adjustment for sociodemographics, lifestyle characteristics, comorbidities, and medications (adjusted odds ratio (AOR) = 1.23 (95% confidence interval (CI) 1.06, 1.42). Elders with OA and pain at baseline were significantly more likely to be diagnosed with incident ADRD than were those without OA or pain (AOR = 1.31, CI 1.08, 1.58). Sensitivity analyses yielded similar findings. Inclusion of depression/anxiety, but not sleep disorders, substantially attenuated these associations. CONCLUSION Findings of this study suggest that OA is associated with elevated ADRD risk, this association is particularly pronounced in those with OA and pain, and mood disorders may partially mediate this relationship.BACKGROUND Significant reduction of dynamic vasomotor reactivity (DVR) was recently reported in patients with amnestic mild cognitive impairment (MCI) relative to age-matched controls. These results were obtained via a novel approach that utilizes data-based predictive dynamic models to quantify DVR. OBJECTIVE Using the same methodological approach, we seek to quantify the dynamic effects of the CO2-driven chemoreflex and baroreflex upon heart-rate in order to examine their possible correlation with the observed DVR impairment in each MCI patient. METHODS The employed approach utilizes time-series data to obtain subject-specific predictive input-output models of the dynamic effects of changes in arterial blood pressure and end-tidal CO2 (putative "inputs") upon cerebral blood flow velocity in large cerebral arteries, cortical tissue oxygenation, and heart-rate (putative "outputs"). RESULTS There was significant dysregulation of CO2-driven heart-rate chemoreflex (p = 0.0031), but not of baroreflex (p = 0.5061), in MCI patients relative to age-matched controls. The model-based index of CO2-driven heart-rate chemoreflex gain (CRG) correlated significantly with the DVR index in large cerebral arteries (p = 0.0146), but not with the DVR index in small/micro-cortical vessels (p = 0.1066). This suggests that DVR impairment in small/micro-cortical vessels is not mainly due to CO2-driven heart-rate chemoreflex dysregulation, but to other factors (possibly dysfunction of neurovascular coupling). CONCLUSION Improved delineation between MCI patients and controls is achieved by combining the DVR index for small/micro-cortical vessels with the CRG index (p = 2×10-5). There is significant correlation (p  less then  0.01) between neuropsychological test scores and model-based DVR indices. Combining neuropsychological scores with DVR indices reduces the composite diagnostic index p-value (p∼10-10).