OBJECTIVE To examine the utility of a novel “cognitive stress test” to detect subtle cognitive impairments and amyloid load within the brains of neuropsychologically normal community-dwelling elders. DESIGN Participants diagnosed as cognitively normal (CN), subjective memory impairment (SMI), mild cognitive impairment (MCI) and pre-clinical mild cognitive impairment (PreMCI) were administered the LASSI-L, a sensitive test of proactive semantic interference (PSI), retroactive semantic interference and uniquely, the ability to recover from the effects of PSI. SETTING Ninety-three subjects (31 males and 62 females) were recruited from three academic institutions in a research consortium. A subset of these individuals underwent F-18 Florbetapir PET scanning. MEASURES Relative percentages of impairment for each diagnostic group on the LASSI-L were calculated by chi-square and Fisher's Exact Test. Spearman's rho was employed to examine associations between amyloid load, and different cognitive measures. RESULTS LASSI-L deficits were identified among 89% of those with MCI, 47% with PreMCI, 33% with SMI and 13% of those classified as CN. CN subjects had no difficulties with recovery from PSI while SMI, preMCI and MCI participants evidenced deficits in recovery from PSI effects. Among a subgroup of participants with normal scores on traditional neuropsychological tests, the strong associations were between the failure to recover from theeffects of PSI and amyloid load in the brain. CONCLUSIONS Failure to recover or compensate for the effects of PSI on the LASSI-L distinguishes the LASSI-L from other widely used neuropsychological tests and appears to be sensitive to subtle cognitive impairments and increasing amyloid load.

SignificanceAlzheimer’s disease (AD) is an age-related neurodegenerative disease. Genome-wide association studies predominately focusing on Caucasian populations have identified risk loci and genes associated with AD; the majority of these variants reside in noncoding regions with unclear functions. Here, we report a whole-genome sequencing study for AD in the Chinese population. Other than the APOE locus, we identified common variants in GCH1 and KCNJ15 that show suggestive associations with AD. For these two risk variants, an association with AD or advanced onset of disease can be observed in non-Asian AD cohorts. An association study of risk variants with expression data revealed their modulatory effects on immune signatures, linking the potential roles of these genes with immune-related pathways during AD pathogenesis.

Quetiapine is suggested to be effective treatment of youths with psychotic disorders and to have a favorable side-effect profile.

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