Results support the feasibility and both the ecological and construct validity of the Virtual Shop.

Only a limited number of studies have investigated the decline of discrete cognitive domains as individuals progress from mild cognitive impairment (MCI) to dementia. Thus, the goal of this longitudinal study was to evaluate the cognitive changes underway during the years preceding a diagnosis of probable Alzheimer’s disease (AD), and to compare these changes to those found in MCI participants who do not progress to dementia. Participants were compared as a function of whether they later converted to AD (n = 47) or not (n = 74). Cognitive change was assessed prior to the conversion year, using that year as a starting point. A combination of polynomial regression analyses and mixed ANOVAs assessed 1) the trajectory of cognitive decline for each domain and 2) the differences between non-progressors and those who had converted to AD. The different cognitive domains demonstrated very different patterns of decline in the group of MCI progressors. A quadratic function, i.e., many years of stable performance followed by a rapid decline just prior to diagnosis, was observed for delayed recall, working memory, and spatial memory. In contrast, a gradual linear decline was observed for immediate recall, executive function, and visuo-spatial abilities. Finally, language in progressors was impaired on all time periods relative to non-progressors, but there was no further change between the first assessments and conversion to AD. Individuals with MCI who progress to AD show abnormal cognition at least two years prior to their dementia diagnosis. The pattern of symptom change observed appears to depend upon the cognitive domain and thus, clinical studies should not assume similar rate of decline across domains. In contrast and, apart from verbal memory, the non-progressors present a performance similar to that of healthy older adults.

ObjectivesThe main objective was to determine the trajectory of instrumental activities of daily living (iADL) decline in persons with mild cognitive impairment (MCI) who progressed towards dementia relative to persons with MCI who remained stable.Methods/DesignAt study entry, 121 participants met criteria for MCI. Based on the follow‐up, 47 participants later converted to dementia and were identified as progressors. Sixteen participants, identified as decliners, presented a significant cognitive decline but did not reach the criteria for dementia within the study timeframe. Stable MCI remained cognitively stable during the 5‐year follow‐up; n = 58. Participants completed a yearly assessment using clinical tests/questionnaires, neuropsychological measures, and functional autonomy assessment until they met criteria for dementia. The average number of months for the follow‐up was 34.ResultsMany years of stable performance followed by an accelerated decline just prior to diagnosis, was observed for complex activities for progressors. No change was found for stable MCI and a gradual linear decline characterized decliners. The housekeeping‐related activities component showed a linear decline in progressors and did not change in stable and decliner MCI. We found a predictive model that includes significant predictors of dementia conversion with a high diagnostic accuracy the following year (area under the curve = 0.94 [95% confidence level; lower bound: 0.87, upper bound: 1]).ConclusionsIt is critical to assess iADL that reflect complex activities in the evaluation of MCI individuals as their impairment, combined with change on cognitive markers, indicates a higher risk of dementia progression 1 or 2 years later.

Background Little is known regarding the dose‐response function in multidomain interventions for dementia prevention. Method The Multidomain Alzheimer Preventive Trial is a 3‐year randomized controlled trial comprising cognitive training, physical activity, nutrition, and omega‐3 polyunsaturated fatty acids for at‐risk older adults. The dose delivered (number of sessions attended) was modeled against global cognition, memory, and fluency in 749 participants. Interaction effects were assessed for age, sex, education, dementia score (CAIDE), frailty score, and apolipoprotein E (APOE) ε4 status. Results The dose‐response models were non‐linear functions indicating benefits up to about 12 to 14 training hours or 15 to 20 multidomain sessions followed by a plateau. Participants who benefited from a higher dose included women, younger participants, frail individuals, and those with lower education or lower risk of dementia. Discussion The non‐linear function indicates that a higher dose is not necessarily better in multidomain interventions. The optimal dose was about half of the potentially available sessions.

Highlights Higher reserve scores relate to activation of the right inferior temporal gyri. Higher reserve scores relate to activation of the left occipital fusiform gyri. The temporal activation moderates the effect of hippocampal volume on memory. Recruitment of the temporal lobe protects against hippocampal atrophy. Temporal activation supports cognitive reserve to sustains memory performance.

Profilin plays an important role in actin organization in all eukaryotic cells through mechanisms that are still poorly understood. We had previously shown that Mid2p, a transmembrane protein and a potential cell wall sensor, is an effective multicopy suppressor of the profilin-deficient phenotype in Saccharomyces cerevisiae. To better understand the role of Mid2p in the organization of the actin cytoskeleton, we isolated five additional multicopy suppressors of pfy1Δ cells that are Rom1p, Rom2p, Rho2p, Smy1p, and the previously uncharacterized protein Syp1p. The problems of caffeine and NaCl sensitivity, growth defects at 30° and 37°, the accumulation of intracellular vesicular structures, and a random budding pattern in pfy1Δ cells are corrected by all the suppressors tested. This is accompanied by a partial repolarization of the cortical actin patches without the formation of visible actin cables. The overexpression of Mid2p, Rom2p, and Syp1p, but not the overexpression of Rho2p and Smy1p, results in an abnormally thick cell wall in wild-type and pfy1Δ cells. Since none of the suppressors, except Rho2p, can correct the phenotype of the pfy1-111/rho2Δ strain, we propose a model in which the suppressors act through the Rho2p signaling pathway to repolarize cortical actin patches.

Abstract. Only a limited number of studies have investigated the decline of discrete cognitive domains as individuals progress from mild cognitive impairment (MCI) to dementia. Thus, the goal of this longitudinal study was to evaluate the cognitive changes underway during the years preceding a diagnosis of probable Alzheimer's disease (AD), and to compare these changes to those found in MCI participants who do not progress to dementia. Participants were compared as a function of whether they later converted to AD (n = 47) or not (n = 74). Cognitive change was assessed prior to the conversion year, using that year as a starting point. A combination of polynomial regression analyses and mixed ANOVAs assessed 1) the trajectory of cognitive decline for each domain and 2) the differences between non-progressors and those who had converted to AD. The different cognitive domains demonstrated very different patterns of decline in the group of MCI progressors. A quadratic function, i.e., many years of stable performance followed by a rapid decline just prior to diagnosis, was observed for delayed recall, working memory, and spatial memory. In contrast, a gradual linear decline was observed for immediate recall, executive function, and visuo-spatial abilities. Finally, language in progressors was impaired on all time periods relative to non-progressors, but there was no further change between the first assessments and conversion to AD. Individuals with MCI who progress to AD show abnormal cognition at least two years prior to their dementia diagnosis. The pattern of symptom change observed appears to depend upon the cognitive domain and thus, clinical studies should not assume similar rate of decline across domains. In contrast and, apart from verbal memory, the non-progressors present a performance similar to that of healthy older adults.

Background: Dose is a critical factor examined in pharmacological treatment. However, little is known about the optimal dosage for non-pharmacological multidomain interventions as well as the function that relates dose to improvement. These gaps have been assessed in this present study in interaction with individual characteristics, which may moderate the effect of dose. Magnification models predict that healthier individuals will benefit more from prolonged practice, whereas reserve models predict that training will reduce cognitive disadvantage. Method:The data from the Multidomain Alzheimer Preventive Trial (MAPT) was used to determine the relationship between cognitive training dose and cognition, and its interaction with sex, age, education, entry criteria, CAIDE risk score, frailty and Apoe4 status. The MAPT is a three-year randomized controlled trial, which includes cognitive training, physical activity, nutrition and omega-3 polyunsaturated fatty acids in at-risk individuals. The number of hours of cognitive training attended (max.=28) was used as a measure of dose in the 749 participants randomized to the multidomain intervention.