It has been shown that older adults perform less well than younger adults on the Iowa Gambling Task (IGT), a real-world type decision-making task that factors together reward, punishment, and uncertainty. To explore the reasons behind this age-related decrement, we administered to an adult life-span sample of 265 healthy participants (median age = 62.00 +/− 16.17 years; range [23–88]) two versions of the IGT, which have different contingencies for successful performance: A'B'C'D' requires choosing lower immediate reward (paired with lower delayed punishment); E'F'G'H' requires choosing higher immediate punishment (paired with higher delayed reward). There was a significant negative correlation between age and performance on the A'B'C'D' version of the IGT (r = −.16, p = .01), while there was essentially no correlation between age and performance on the E'F'G'H' version (r = −.07, p = .24). In addition, the rate of impaired performance in older participants was significantly higher for the A'B'C'D' version (23%), compared to the E'F'G'H' version (13%). A parsimonious account of these findings is an age-related increase in hypersensitivity to reward, whereby the decisions of older adults are disproportionately influenced by prospects of receiving reward, irrespective of the presence or degree of punishment.

Our findings suggest that changes of everyday behavior are detectable in accelerometric behavior protocols even in the absence of major clinical behavioral impairments in AD.

In vivo imaging of amyloid-β (Aβ) load as a biomarker of Alzheimer's disease (AD) would be of considerable clinical relevance for the early diagnosis and monitoring of treatment effects. Here, we investigated automated quantification of in vivo T2 relaxation time as a surrogate measure of plaque load in the brains of ten AβPP/PS1 transgenic mice (age 20 weeks) using in vivo MRI acquisitions on a 7T Bruker ClinScan magnet. AβPP/PS1 mice present with rapid-onset cerebral β-amyloidosis, and were compared with eight age-matched, wild-type control mice (C57Bl/6J) that do not develop Aβ-deposition in brain. Data were analyzed with a novel automated voxel-based analysis that allowed mapping the entire brain for significant signal changes. In AβPP/PS1 mice, we found a significant decrease in T2 relaxation times in the deeper neocortical layers, caudate-putamen, thalamus, hippocampus, and cerebellum compared to wildtype controls. These changes were in line with the histological distribution of cerebral Aβ plaques and activated microglia. Grey matter density did not differ between wild-type mice and AβPP/PS1 mice, consistent with a lack of neuronal loss in histological investigations. High-field MRI with automated mapping of T2 time changes may be a useful tool for the detection of plaque load in living transgenic animals, which may become relevant for the evaluation of amyloid lowering intervention effects in future studies.

Transcranial magnetic stimulation (TMS) provides evidence for facilitatory and inhibitory motor dysfunctions in Alzheimer's disease (AD). The corpus callosum (CC) is affected in AD already at early stages consistent with the hypothesis that AD patients exhibit alterations in transcallosally mediated motor inhibition (ipsilateral silent period, iSP). Therefore, here we aimed at investigating the integrity not only of intra-, but also of inter-hemispheric mechanisms of cortical motor excitability in AD. We determined the iSP, the resting motor threshold (RMT), and the amplitude of motor evoked potentials (MEP) in 19 AD patients and 19 healthy controls using single-pulse TMS. Furthermore, we used paired-pulse TMS to study the intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF). All subjects underwent comprehensive neuropsychologic, clinical, and laboratory testing, and neuroimaging to exclude significant co-morbidity. In AD patients, the RMT was significantly reduced (Oneway-ANOVA). An analysis of covariance (ANCOVA) revealed a strong group specific interaction of the inhibitory interstimulus intervals (p = 0.005) with a reduced ICI in AD. Furthermore, we found a significantly prolonged iSP-latency (p = 0.003) in AD compared to controls, whereas the iSP-duration was not different. The iSP-latency correlated significantly with the ICI (ANCOVA) (p = 0.02). The ICF did not differ significantly between groups. Our data suggest comprehensive but still subclinical dysfunctions of motor cortical inhibition in mild to moderate clinical stages of AD with strong interactions of intra- and inter-hemispheric inhibitory phenomena. Future studies are needed to show the potential prognostic relevance of these findings for the further course of the disease.

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