Impaired comprehension of metaphorical expressions in very mild Alzheimer's disease.

BACKGROUND: Brain-damaged patients often have difficulty understanding non-literal language. However, whether patients with Alzheimer's disease (AD) have comprehension deficits of metaphorical expressions, in contrast with non-metaphorical (literal) expressions, remains unclear. PATIENTS AND METHODS: The subjects were 40 AD patients; 20 had mild AD (17-23 points on the Mini-Mental State Examination [MMSE]), and 20 had very mild AD (≥24 points). Twenty normal elderly controls were also enrolled as a control group. Thirty sentences that contained novel similes (Items) were prepared. For each Item, four explanatory choices, consisting of one correct response and three foils, were provided. The participants were asked to choose the written statement that best represented the Item's meaning. In addition, all the subjects completed the Token Test. RESULTS: The patients with mild AD had significantly lower scores than the normal controls on both the simile comprehension test and the Token Test. However, the patients with very mild AD exhibited significantly lower scores on the simile comprehension test, but not on the Token Test. The distributions of error types for the simile test differed between the mild AD group and the other groups. The mild AD patients made more errors that were "far" from the correct responses. CONCLUSION: Patients with AD are more likely to have comprehension deficits of metaphorical expressions than comprehension deficits of non-metaphorical expressions. Pragmatic language dysfunction may precede formal language dysfunction during the progression of AD.

Lack of genetic association between TREM2 and late-onset Alzheimer's disease in a Japanese population.

Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002-0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.

SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.

To discover susceptibility genes of late-onset Alzheimer's disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values <2×10(-5) were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P = 7.33×10(-7) in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P = 1.77×10(-9)) and rs3781834 (P = 1.04×10(-8)). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P = 1.71×10(-5)) and rs744373 near BIN1 (P = 1.39×10(-4)). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations.

Metabolic syndrome is a risk factor for acute cerebral infarction in a younger elderly Kurashiki population.

This study evaluated the association between metabolic syndrome as defined by Japanese criteria and its diagnostic components (visceral obesity, dyslipidemia, hypertension, and impaired glucose tolerance) and acute cerebral infarction in younger elderly (age 50-74 years) and the older elderly (age ≥75 years) persons living in the Japanese city of Kurashiki. We studied 73 patients aged ≥50 years (44 of them aged ≥75 years) admitted to our hospital with acute cerebral infarction and 323 control subjects aged ≥50 years (52 aged ≥75 years) who underwent medical checkup of the brain in our hospital. Types of cerebral infarction included atherothrombotic (27 patients), lacunar (24 patients), cardioembolic (19 patients), and other types (3 patients). Metabolic syndrome was defined based on the Japanese criteria. In multiple logistic regression analysis, among the 29 younger elderly patients aged 50-74 years, dyslipidemia, hypertension, and impaired glucose tolerance as diagnostic components of metabolic syndrome, and metabolic syndrome itself were significantly related to acute cerebral infarction (adjusted odds ratio [OR], 5.664, 4.869, 3.390, and 3.214, respectively). Among the 44 older elderly patients aged ≥75 years, dyslipidemia was significantly related to acute cerebral infarction (OR, 4.193). However, metabolic syndrome was not a significant risk factor for acute cerebral infarction, even when patients with cardioembolic and other types of infarction were excluded. These data suggest that metabolic syndrome as defined by Japanese criteria is an independent risk factor for acute cerebral infarction in the younger elderly, but not the older elderly, Kurashiki population.