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Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.

Although the pathogenesis underlying behavioral variant frontotemporal dementia (bvFTD) has yet to be fully understood, glutamatergic abnormalities have been hypothesized to play an important role. The aim of the present study was to determine the availability of the metabotropic glutamate receptor type 5 (mGluR5) using a novel positron emission tomography (PET) radiopharmaceutical with high selectivity for mGluR5 ([(11)C]ABP688) in a sample of bvFTD patients. In addition, we sought to determine the overlap between availability of mGluR5 and neurodegeneration, as measured using [(18)F]FDG-PET and voxel-based morphometry (VBM). Availability of mGluR5 and glucose metabolism ([(18)F]FDG) were measured in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [(11)C]ABP688 binding potential maps (BPND) were calculated using the cerebellum as a reference region, with [(18)F]FDG standardized uptake ratio maps (SUVR) normalized to the pons. Grey matter (GM) concentrations were determined using VBM. Voxel-based group differences were obtained using RMINC. BvFTD patients showed widespread decrements in [(11)C]ABP688 BPND throughout frontal, temporal and subcortical areas. These areas were likewise characterized by significant hypometabolism and GM loss, with overlap between reduced [(11)C]ABP688 BPND and hypometabolism superior to that for GM atrophy. Several regions were characterized only by decreased binding of [(11)C]ABP688. The present findings represent the first in vivo report of decreased availability of mGluR5 in bvFTD. This study suggests that glutamate excitotoxicity may play a role in the pathogenesis of bvFTD and that [(11)C]ABP688 may prove a suitable marker of glutamatergic neurotransmission in vivo. published

This study investigates the associations between the different symptom dimensions of schizophrenia and neuropsychological performances. Globally, the results replicate previously described associations. The "negative" dimension correlates with impaired sustained attention and working memory, thus suggestive of dorsolateral frontal cortex dysfunction. "Disorganization" correlates with the ability to inhibit proactive interference. thus with ventromedial frontal dysfunction. The results also add support to the view that the "psychotic" dimension described in three-dimension models includes in fact two distinct dimensions, (1) "hallucinations," here associated to episodic memory measures, and (2) "delusions", here associated to visuospatial attention, thus suggestive of mediotemporal and posterior neocortical dysfunction, respectively.

This study investigated the neural and cognitive correlates of reality distortion in schizophrenia by using event-related potentials (ERPs) recorded in a recognition memory task for face. This task has been chosen because previous studies have shown that it provides distinct indices related to specific cognitive processes and to the functioning of specific brain regions. ERPs have been recorded in controls and schizophrenia patients separated into high scorers (RD+) and low-scorers (RD-) according to their Reality Distortion score (hallucination and delusion SAPS subscales). The results indicate that RD+ presents abnormalities on various cognitive processes. First, RD+ are deficient at interference inhibition and knowledge integration (reduced P2a and N400 effect). The similar impairments found in RD- suggest that they represent basic traits of the illness. Second, RD+ showed inappropriate stimulus categorization and contextual integration (larger N300 and fronto-central effect). Third, RD+ showed a late index (P600 effect) not different from controls, but larger than in RD-. This result is consistent with a qualitative, rather than quantitative, impairment of mnemonic binding processes (inappropriate binding) in RD+. Since each of the ERP abnormalities observed represents associated with distinct brain dysfunction, the results are further discussed in regard of the respective contribution of the parietal, frontal and hippocampal structures to reality distortion symptoms.

Although memory impairment is recognized as a major fact of schizophrenia, only a few studies have investigated memory impairments with specifically designed event-related potential (ERP) protocols. In this study, ERPs were recorded from 15 schizophrenia patients and 15 matched control subjects during implicit and explicit memory tasks for unfamiliar faces. The results showed that patients have a reduced modulation of an N400-like component in both the implicit and explicit tasks that suggests a deficient integration of incoming information with personal knowledge. Patients also displayed an enhanced frontally distributed activity in the explicit task that may represent an impairment in the integration of intrinsic contextual information, a disturbance in the ability to inhibit proactive interference or a combination of both processes. Finally, the modulation of the late positive component did not differ from that in control subjects in both implicit and explicit tasks, suggesting that the impairment in mnemonic binding processes suggested in schizophrenia is more qualitative, i.e. incomplete or inappropriate, due to the anomalies in antecedent processes. The correlations observed between impairments of ERP modulation and symptoms further support these interpretations.