Frontobasal gray matter loss is associated with the TREM2 p.R47H variant.

A rare heterozygous TREM2 variant p.R47H (rs75932628) has been associated with an increased risk for Alzheimer's disease (AD). We aimed to investigate the clinical presentation, neuropsychological profile, and regional pattern of gray matter and white matter loss associated with the TREM2 variant p.

Selective brain gray matter atrophy associated with APOE ε4 and MAPT H1 in subjects with mild cognitive impairment.

The aim of our study was to elucidate whether specific patterns of gray matter loss were associated with apolipoprotein E ε4 (APOE ε4) and microtubule-associated protein tau (MAPT)-H1) genetic variants in subjects with mild cognitive impairment (MCI) at a baseline visit. Gray matter voxel-based morphometry analysis of T1 magnetic resonance imaging scans were performed in 65 amnestic-MCI subjects. MCI APOE ε4 carriers compared with non-carriers showed increased brain atrophy in right hippocampus and rostral amygdala, superior and middle temporal gyrus, and right parietal operculum, including inferior frontal gyrus, inferior parietal, and supramarginal gyrus.

Posterior parietooccipital hypometabolism may differentiate mild cognitive impairment from dementia in Parkinson's disease.

Purpose: Patients with Parkinson's disease (PD) may have normal cognition, mild cognitive impairment (MCI) or dementia. We investigated differences in cerebral metabolism associated with these three cognitive states and the relationship between metabolism and cognitive dysfunction.

Methods: FDG PET and a battery of neuropsychological tests were used to study PD patients with dementia (n = 19), MCI (n = 28) and normal cognition (n = 21), and control subjects (n = 20).

Genetic variation in APOE cluster region and Alzheimer's disease risk.

We report the fine mapping/sequencing results of promoter and regulatory regions of APOE cluster genes (APOE, APOC1, APOC4, APOC2, and TOMM40) in Alzheimer's disease (AD) risk as well as in the progression from mild cognitive impairment (MCI) to AD. Long-range sequencing in 29 MCI subjects who progressed to dementia revealed 7 novel variants. Two potentially relevant novel variants and 34 single nucleotide polymorphisms (SNPs) were genotyped in a large sample of AD, MCI, and control subjects (n = 1453).

The effect of MAPT H1 and APOE ε4 on transition from mild cognitive impairment to dementia.

Microtubule-associated protein tau (MAPT) and apolipoprotein E (APOE) are involved in the pathogenic mechanisms of Alzheimer's disease (AD). We prospectively followed three longitudinal independent samples (total n=319) with amnestic mild cognitive impairment (MCI) and analyzed whether MAPT H1/H2 haplotypes and APOE ε4 polymorphisms accelerated the rate of progression from MCI to dementia. At the end of the study, 172 subjects remained cognitively stable, whereas 147 progressed to dementia.

Homocysteine and cognitive impairment in Parkinson's disease: a biochemical, neuroimaging, and genetic study.

The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed.