C9orf72 Repeat Expansion Does Not Affect the Phenotype in Primary Progressive Aphasia.

Primary progressive aphasia (PPA) forms the spectrum of language variants of frontotemporal lobar degeneration (FTLD), including three subtypes each consisting of distinctive speech and language features. Repeat expansion in C9orf72 gene is the most common genetic cause of FTLD. However, thus far only little is known about the effects of the C9orf72 repeat expansion on the phenotype of PPA. This retrospective study aimed at determining the differences between the PPA phenotypes of the C9orf72 expansion carriers and non-carriers. Our results demonstrated no significant differences between these groups, indicating that the C9orf72 repeat expansion does not substantially affect the phenotype of PPA.

A specific cognitive deficit within semantic cognition across a multi-generational family.

We report a study of eight members of a single family (aged 8-72 years), who all show a specific deficit in linking semantic knowledge to language. All affected members of the family had high levels of overall intelligence; however, they had profound difficulties in prose and sentence recall, listening comprehension and naming. The behavioural deficit was remarkably consistent across affected family members. Structural neuroimaging data revealed grey matter abnormalities in the left infero-temporal cortex and fusiform gyri: brain areas that have been associated with integrative semantics. This family demonstrates, to our knowledge, the first example of a heritable, highly specific abnormality affecting the interface between language and cognition in humans and has important implications for our understanding of the genetic basis of cognition.

Cognitive impairment in Alzheimer's disease is modified by APOE genotype.

AIM: We examined whether impairment in specific cognitive domains in Alzheimer's disease (AD) differed according to APOE genotype and age at onset. METHODS: Cognitive functions of 229 consecutive AD patients were assessed using Visual Association Test (VAT), Memory Impairment Screen+ (MIS+), VAT object naming, fluency test and Trail Making Test (TMT). Dementia severity was assessed using MMSE. ANOVAs were performed with APOE genotype and age at onset as independent variables and sex, education and MMSE as covariates. RESULTS: 28% of patients were APOE epsilon4-negative, 58% heterozygous and 14% homozygous. A significant association between APOE genotype and VAT and MIS+ was found when correcting for sex and education. An interaction effect between APOE genotype and age at onset on VAT and VAT object naming was found, with young carriers performing worse than young noncarriers. By contrast, when additionally correcting for MMSE, a significant association between APOE genotype and VAT object naming, TMT-A and TMT-B was found, with noncarriers performing worse than carriers. CONCLUSION: Memory was more impaired among APOE epsilon4 carriers than among noncarriers. By contrast, naming, executive functions and mental speed were more impaired among APOE epsilon4 noncarriers. This suggests that the APOE genotype modifies the clinical phenotype in terms of cognitive impairment in AD.

Progressive anomia revisited: focal degeneration associated with progranulin gene mutation.

In 2003 we reported a case study of a patient, Newton who presented with a progressive circumscribed anomia in association with focal left hemisphere atrophy. Remarkably, he could spell aloud the names of objects that he could not name, indicating dissociated access to phonology and orthography. We now present follow-up clinical data, post-mortem histopathological findings, and results of molecular genetic analysis. Newton showed tau-negative ubiquitin-positive histology consistent with frontotemporal lobar degeneration (FTLD) and a mutation in the progranulin (PGRN) gene. The case exemplifies the heterogeneity of clinical expression of FTLD and contributes to understanding of primary progressive aphasia.

[Performance of carriers and non-carriers of the E280A mutation for familial Alzheimer's disease in a naming test]. / Desempeño de portadores y no portadores de la mutación E280A para enfermedad de Alzheimer familiar en una prueba de denominación.

INTRODUCTION: Early preclinical diagnosis is the greatest challenge faced by researchers into dementia. Cognitive, neuroanatomical, neurophysiological and genetic markers have been reported. One of the preclinical cognitive markers is anomia and it is often assessed using visual naming tests. AIMS: The aim of this study was to analyse the type of mistakes made in a visual naming test in a group of carriers and non-carriers of the E280A PS1 mutation. PATIENTS AND METHODS: The sample was made up of 91 participants who were genotyped for the E280A PS1 mutation and divided into three groups: non-carriers (n = 30), asymptomatic carriers (n = 39) and sick carriers (n = 22). Selection was performed using the Minimental and the Fast and EDG scales and mistakes in the CERAD naming test were classified. The types of mistakes taken into account were: no answer, visual, semantic, phonological, the whole for the part, and not related. RESULTS: There is a significant difference in the number of semantic errors between non-carriers and asymptomatic carriers; on comparing the three groups, no statistically significant differences were found in visual mistakes. CONCLUSIONS: Visual mistakes are a general characteristic, even in healthy subjects and, therefore, these errors did not provide any information that could be used to classify patients with or without dementia. Semantic mistakes can be considered as being a preclinical sign in familial Alzheimer's disease (FAD). Both visual and auditory naming tests must be applied when evaluating patients with FAD.

Etiology of reading difficulties and rapid naming: the Colorado Twin Study of Reading Disability.

Children with reading deficits perform more slowly than normally-achieving readers on speed of processing measures, such as rapid naming (RN). Although rapid naming is a well-established correlate of reading performance and both are heritable, few studies have attempted to assess the cause of their covariation. Measures of rapid naming (numbers, colors, objects, and letters subtests), phonological decoding, orthographic choice, and a composite variable (DISCR) derived from the reading recognition, reading comprehension, and spelling subtests of the Peabody Individual Achievement Test were obtained from a total of 550 twin pairs with a positive school history of reading problems. Basic DeFries and Fulker (DF) multiple regression models for the analysis of selected twin data confirmed the heritable nature of phonological decoding, orthographic choice, DISCR, and rapid-naming composites. Bivariate DF models were employed to examine the extent to which deficits in the three reading-related measures covary genetically with rapid naming. Significant bivariate heritability estimates for each of the reading measures with the numbers and letters rapid-naming composite were also obtained. As expected, univariate sib-pair linkage analyses indicated the presence of a quantitative trait locus (QTL) on chromosome 6p21.3 for phonological decoding and orthographic choice deficits. Bivariate linkage analyses were then conducted to test the hypothesis that this QTL for reading difficulties is pleiotropic for slower performance on RN tasks. The results obtained from these analyses did not provide substantial evidence that the 6p QTL for reading difficulties has significant effects on rapid naming; however, larger samples would be required to test this hypothesis more rigorously.