Older and Wiser: Interpretation of Proverbs in the Face of Age-Related Cortical Atrophy.

In the present study, we investigated whether interpretation of proverbs differs across the lifespan and if so, whether it is associated with age-related fronto-temporal atrophy. Using a sample of 333 healthy individuals aged 18-89 years, we found a significant effect of age on proverb interpretation [H(2) = 12.001, p = 0.002]: old adults (OA) were better than young adults (YA) (p = 0.002), and so were middle-aged-adults (MA) (p = 0.005). OA and MA had significantly less grey matter (GM) than YA in frontal and temporal lobes bilaterally, and OA less than MA in the right temporal lobe. GM volumes in these regions did not moderate the effect of age on the proverbs scores. The whole-brain analysis of groups' GM maps revealed that the proverbs scores were associated with more GM in YA relative to OA in the right middle temporal gyrus, which is consistent with evidence on the role of this area in processing of unfamiliar proverbs. Overall, our data suggest that interpretation of proverbs is well preserved in late adulthood, despite considerable age-related cortical atrophy.

Dorsal White Matter Integrity and Name Retrieval in Midlife.

BACKGROUND: Recent findings on retrieval of proper names in cognitively healthy middle- aged persons indicate that Tip-Of-The-Tongue (TOT) states occurring during proper name retrieval implicate inferior frontal (BA 44) and parietal (BA 40) cortical areas. Such findings give rise to the possibility that anatomical connectivity via dorsal white matter may be associated with difficulties in name retrieval in midlife. OBJECTIVES & METHOD: Using Diffusion Tensor Imaging, we examined in vivo microstructural properties of white matter in 72 cognitively healthy Middle-Aged (MA) and 59 Young Adults (YA), comparing their naming abilities as well as testing, for possible associations between dorsal white matter integrity and naming abilities in the MA group. RESULTS: The MA group was better in retrieving correct names (U = 1525.5, p = .006), but they also retrieved more incorrect names than YA believing they had retrieved the correct ones (U = 1265.5, p < .001). Furthermore, despite being more familiar with the tested names than YA (U = 930, p < .001), MA experienced significantly more TOTs relative to YA (U = 1498.5, p = .004). Tract-based spatial statistics showed significant group differences in values of fractional anisotropy (FA), mean diffusivity, axial diffusivity, radial diffusivity, and mode of anisotropy in a range of white matter tracts. In the MA group, FA values in the right Superior Longitudinal Fasciculus (SLF) were positively correlated with "don't know" scores (rs = .287, p = .014). CONCLUSION: The association of SLF integrity and name retrieval ability in midlife indicates a need to revisit the models of name retrieval that posit no role for dorsal white matter in proper name retrieval.

In search for common patterns in aphasia: The case of Spanish wh-dependencies.

BACKGROUND: Research on comprehension of wh-dependencies in Broca's aphasia has resulted in discrepant findings, suggesting that structurally different languages may involve different comprehension patterns. AIMS: In the present study, we investigated whether Spanish speakers with Broca's aphasia rely on a language-specific cue that might facilitate comprehension of object wh-dependencies - the preposition a. Since the preposition a in Spanish indicates animate objects, reliance on this cue would facilitate comprehension of more demanding object wh-dependencies, cancelling out processing differences between structures with subject and object extractions. METHODS: We studied comprehension of subject vs. object quién ("who") and qué ("which") direct and embedded questions, and relative clauses introduced by que in seven speakers with aphasia (SWA): six with Broca's and one with mixed aphasia. Control data were obtained from ten neurologically intact elderly Spanish speakers. RESULTS: Mann-Whitney test revealed that compared to healthy controls, SWA had preserved comprehension of both subject and object who direct questions, object which direct questions, and object relative clauses. However, they exhibited considerably worse comprehension of subject which direct questions, all embedded questions regardless of the extraction site (subject, object) or type of wh-word (who, which), and subject relative clauses. Individual comprehension profiles obtained in a modified t-test and revised standardized difference test, while containing some variability, largely support lack of subject-object asymmetry and objects-better patterns. Furthermore, in direct questions, comprehension of who questions was better than the comprehension of which questions, while the opposite was found in embedded questions. CONCLUSIONS: The lack of significant subject-object asymmetry in most conditions, together with better comprehension of object than subject extractions in direct questions, indicates that Spanish SWA rely on the preposition a in the comprehension of object wh-dependencies. However, this strategy fails in more complex conditions (embedded questions), because the processing costs outweigh the facilitating effects of this cue, unless additional cues to the object are present (object relatives). The present findings have implications for the accounts of wh-dependencies in Broca's aphasia involving Discourse-linking, the Intervener hypothesis, and the Competition model.

Proper name retrieval and structural integrity of cerebral cortex in midlife: A cross-sectional study.

There is currently little understanding on whether retrieval of proper names differs in midlife compared to young adulthood and if so, whether the age differences in this ability are associated with differences in structural integrity of the cerebral cortex. To answer these questions, we studied retrieval of proper names in 115 cognitively healthy middle-aged persons (49.7, ±3.2), comparing their performance on a tip-of-the-tongue (TOT) task with that of 68 young persons (25.4, ±3.5) from the Cam-Can data repository (http://www.mrc-cbu.cam.ac.uk/datasets/camcan/). Grey matter (GM) density and cortical thickness were used as indices of structural integrity of the cerebral cortex. The middle-aged (MA) group experienced more TOTs during proper names retrieval than young adults (YA), (t = 3.789, p < .005) and had considerably less GM density and cortical thickness across a range of brain areas bilaterally. Small clusters in left BA 45 and right BA 44 (cortical thickness) and in right BA 40 (volumetry) revealed group differences when accounting for TOTs. However, we observed no correlations between MA's TOT scores and GM volumes or cortical thickness of the brain regions typically reported as implicated in retrieval of proper names: left anterior temporal lobe, left insula, and left superior and middle temporal gyri.

Is the left uncinate fasciculus associated with verbal fluency decline in mild Alzheimer's disease?

The association between verbal fluency deficit in Alzheimer's disease (AD) and deterioration of specific white matter (WM) tracts is currently not well understood. Using diffusion tensor imaging, we investigated a possible association between the left uncinate fasciculus, which has been implicated in word retrieval, and verbal fluency deficit in AD. A comparison of five properties of WM (fractional anisotropy, mode of anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) in 28 mild AD patients and 26 age-, gender- and education-matched healthy controls revealed significant group differences in a range of WM tracts. Looking specifically at diffusion parameters' values for the left uncinate fasciculus and verbal fluency scores in the AD group, we observed a positive trend between the letter fluency scores and mode of anisotropy values (r = 0.36, p = 0.55). Thus, our data suggest more global WM damage in mild AD, which also includes damage to the left uncinate fasciculus. However, damage to this particular tract is not robustly associated with verbal fluency decline at this stage of disease.

More than a mere sequence: predictive processing of wh-dependencies in early bilinguals.

The purpose of the present study was to determine whether early bilingual Basque-Spanish speakers, who acquired Spanish by the age of 5, comprehend Spanish wh-dependences as effortlessly as native Spanish speakers. Given that Basque and Spanish are structurally different languages, we hypothesized that predictive processing strategies from the first language (L1) would interfere with predictive processing strategies in the second language (L2). More specifically, since Basque overtly marks the semantic role of agent/subject position, whereas Spanish overtly marks the role of patient/object position, we looked at whether the difference in overt marking of semantic roles would affect comprehension of subject vs. object quien "who" and qué "which" direct and embedded questions as well as subject vs. object relative clauses introduced by qué. The main finding of the study is that overall early Basque-Spanish bilinguals needed more time for the comprehension of wh-dependencies in Spanish compared to native Spanish speakers, as indicated by statistically significant group differences in response times in 9 out of 10 conditions. The results of this exploratory study indicate that a difference in overt marking of semantic roles between the two languages affects the ease of processing of Spanish wh-dependencies in early Basque-Spanish bilinguals, interfering with their ability to make native-like predictions in L2.

Distinct pattern of hypometabolism and atrophy in preclinical and predementia Alzheimer's disease.

The goal of the present study was to determine the earliest patterns of hypometabolism and atrophy in the development of Alzheimer's disease (AD). Stages of AD were defined by positron emission tomography imaging evidence of cortical amyloid pathology in addition to cognitive criteria. Subjects for the study were selected from the Alzheimer's Disease Neuroimaging Initiative database and divided into 4 groups: cognitively normal (CN) amyloid negative (Aß-) elderly subjects (n = 36), CN amyloid-positive (Aß+) (n = 21), early mild cognitive impairment Aß+ (n = 65), and late mild cognitive impairment Aß+ (n = 23) subjects. Region of interest-based (primary) and voxel-based (secondary) analyses were used to assess gray matter hypometabolism, quantified by [18F]fluorodeoxyglucose-positron emission tomography, and decrease in gray matter volume and cortical thickness was measured by magnetic resonance imaging. Region of interest- and voxel-based analyses showed significant hypometabolism but not atrophy in CN Aß+ subjects compared with CN Aß- subjects. The results suggest that hypometabolism exceeds atrophy in preclinical AD, supporting the notion that amyloid load may affect synaptic activity, leading to synaptic loss and subsequent neuronal loss.

Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus.

Primary progressive aphasia (PPA) is characterized by left hemispheric frontotemporal cortical atrophy. Evidence from anatomical studies suggests that the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal forebrain, may be involved in the pathological process of PPA. Therefore, we studied the pattern of cortical and basal forebrain atrophy in 10 patients with a clinical diagnosis of PPA and 18 healthy age-matched controls using high-resolution magnetic resonance imaging (MRI). We determined the cholinergic basal forebrain nuclei according to Mesulam's nomenclature and the NSP in MRI reference space based on histological sections and the MRI scan of a post-mortem brain in cranio. Using voxel-based analysis, we found left hemispheric cortical atrophy in PPA patients compared with controls, including prefrontal, lateral temporal and medial temporal lobe areas. We detected cholinergic basal forebrain atrophy in left predominant localizations of Ch4p, Ch4am, Ch4al, Ch3 and NSP. For the first time, we have described the pattern of basal forebrain atrophy in PPA and confirmed the involvement of NSP that had been predicted based on theoretical considerations. Our findings may enhance understanding of the role of cholinergic degeneration for the regional specificity of the cortical destruction leading to the syndrome of PPA.

The ε4 genotype of apolipoprotein E and white matter integrity in Alzheimer's disease.

BACKGROUND: In this multicenter study, we investigated a possible association between the APOE ε4 allele and white matter (WM) integrity in Alzheimer's disease (AD) using diffusion tensor imaging (DTI). METHODS: We analyzed fractional anisotropy (FA) and mean diffusivity (MD) as indices of WM integrity in 70 AD patients (35 APOE ε4 carriers, 35 noncarriers) and 56 healthy control (HC) subjects (28 APOE ε4 carriers, 28 noncarriers). APOE ε4 carriers and noncarriers were matched for age and gender within each diagnostic group. RESULTS: We found significant effects of diagnosis (Pcorrected < .05 [FWE]; i.e., smaller FA values and larger MD values in AD patients compared with HCs) and significant effects (P < .001) of APOE ε4 carrier status on MD in HCs but not in AD subjects. CONCLUSIONS: The results indicate that APOE ε4 has a moderate effect on WM integrity in HCs, but no effect on WM integrity in manifest AD.