Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy.
Ontology highlight
ABSTRACT:
SUBMITTER: Suarez-Gonzalez A
PROVIDER: S-EPMC4926954 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
Publications
Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy.
Suárez-González Aida A Lehmann Manja M Shakespeare Timothy J TJ Yong Keir X X KXX Paterson Ross W RW Slattery Catherine F CF Foulkes Alexander J M AJM Rabinovici Gil D GD Gil-Néciga Eulogio E Roldán-Lora Florinda F Schott Jonathan M JM Fox Nick C NC Crutch Sebastian J SJ
Neurobiology of aging 20160425
Age at onset (AAO) has been shown to influence the phenotype of Alzheimer's disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age ...[more]
Similar Datasets
Project description:ObjectiveTo investigate association of genetic risk factors for late-onset Alzheimer disease (LOAD) with risk of posterior cortical atrophy (PCA), a syndrome of visual impairment with predominant Alzheimer disease (AD) pathology in posterior cortical regions, and with risk of "posterior AD" neuropathology.MethodsWe assessed 81 participants with PCA diagnosed clinically and 54 with neuropathologic diagnosis of posterior AD vs 2,523 controls for association with 11 significant single nucleotide polymorphisms (SNPs) from published LOAD risk genome-wide association studies.ResultsThere was highly significant association with APOE ε4 and increased risk of PCA (p = 0.0003, odds ratio [OR] = 3.17) and posterior AD (p = 1.11 × 10(-17), OR = 6.43). No other locus was significant after corrections for multiple testing, although rs11136000 near CLU (p = 0.019, OR = 0.60) and rs744373 near BIN1 (p = 0.025, OR = 1. 63) associated nominally significantly with posterior AD, and rs3851179 at the PICALM locus had significant association with PCA (p = 0.0003, OR = 2.84). ABCA7 locus SNP rs3764650, which was also tested under the recessive model because of Hardy-Weinberg disequilibrium, also had nominally significant association with PCA risk. The direction of association at APOE, CLU, and BIN1 loci was the same for participants with PCA and posterior AD. The effects for all SNPs, except rs3851179, were consistent with those for LOAD risk.ConclusionsWe identified a significant effect for APOE and nominate CLU, BIN1, and ABCA7 as additional risk loci for PCA and posterior AD. Our findings suggest that at least some of the genetic risk factors for LOAD are shared with these atypical conditions and provide effect-size estimates for their future genetic studies.
| S-EPMC4001196 | biostudies-literature
Project description:IntroductionIn vivo clinical, anatomical and metabolic differences between posterior cortical atrophy (PCA) patients presenting with different Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers profiles are still unknown.MethodsTwenty-seven PCA patients underwent CSF examination and were classified as 1) PCA with a typical CSF AD profile (PCA-tAD; abnormal amyloid and T-tau/P-tau biomarkers, n = 13); 2) PCA with an atypical AD CSF profile (PCA-aAD; abnormal amyloid biomarker only, n = 9); and 3) PCA not associated with AD (PCA-nonAD; normal biomarkers, n = 5). All patients underwent clinical and cognitive assessment, structural MRI, and a subset of them underwent brain 18F-FDG PET.ResultsAll patients' groups showed a common pattern of posterior GM atrophy and hypometabolism typical of PCA, as well as equivalent demographics and clinical/cognitive profiles. PCA-tAD patients showed a group-specific pattern of hypometabolism in the left fusiform gyrus and inferior temporal gyrus. PCA-aAD did not present a group-specific atrophy pattern. Finally, group-specific gray matter atrophy in the right dorsolateral prefrontal cortex, left caudate nucleus and right medial temporal regions and hypometabolism in the right supplementary motor area and paracentral lobule were observed in PCA-nonAD patients.ConclusionOur findings suggest that both PCA-tAD and PCA-aAD patients are on the AD continuum, in agreement with the recently suggested A/T/N model. Furthermore, in PCA, the underlying pathology has an impact at least on the anatomo-functional presentation. Brain damage observed in PCA-tAD and PCA-aAD was mostly consistent with the well-described presentation of the disease, although it was more widespread in PCA-tAD group, especially in the left temporal lobe. Additional fronto-temporal (especially dorsolateral prefrontal) damage seems to be a clue to underlying non-AD pathology in PCA, which warrants the need for longitudinal follow-ups to investigate frontal symptoms in these patients.
| S-EPMC6197495 | biostudies-literature
Project description:Brain ageing is thought to be related to geriatric depression, but the relationship between ageing and depression among middle aged individuals is unknown. The present study aimed to evaluate whether the age-related reduction of brain cortical thickness (CT) can be found in adult first-episode MDD patients, as well as to identify the possible genetic effect of the ANK3 gene polymorphism age-relates CT reduction. This study recruited 153 first-episode MDD patients with a disease duration < 2 years and 276 healthy controls (HC), and the CT of 68 whole brain regions and two ANK3 SNPs (rs1994336 and rs10994359) were analyzed. The results showed that although the CT of both groups was negative correlated with age, the MDD group had significant greater age-related decrease in CT than the HC group (-9.35 × 10-3 mm/year for MDD vs. -1.23 × 10-3 mm/year for HC in the left lateral orbitofrontal lobe). The multivariate analysis of covariance (MANCOVA) results yielded significant interactions of diagnosis × age, genotype × age and diagnosis × genotype interaction for rs10994359. In HC, the C allele showed a protective effect on age-related CT reduction. The reduction in CT with age was several times as greater in non-C carriers as in C carriers (-3.54 × 10-3 vs.-0.15 × 10-3 mm/year in left supramarginal gyrus) for HC. However, this protective effect disappeared in patients with MDD. We did not find a clear effect of rs1994336 on the age-related CT reduction. The findings indicate that the widespread accelerated brain ageing occurs early in adult-onset depression and this ageing may be a pathological mechanisms of depression rather than an outcome of the disease. The ANK3 rs10994359 polymorphism may partially affect regional cortical ageing in MDD.
| S-EPMC7490581 | biostudies-literature
Project description:ObjectivePosterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are clinical syndromes associated with posterior brain atrophy. We compared PCA and LPA to each other and to an age-matched group of patients with early age at onset of Alzheimer disease (EO-AD). We hypothesized that these 3 syndromes are part of a single clinical and biologic continuum.MethodsVoxel-based morphometry (VBM) was used to assess atrophy in 14 PCA, 10 LPA, and 16 EO-AD patients compared to 65 healthy controls. Genetic analysis for APOE was conducted in 30 patients and 44 controls. Four patients came to autopsy. An additional 14 were studied with the beta-amyloid specific PET with tracer (11)C-labeled Pittsburgh Compound-B (PIB).ResultsVBM results demonstrated that, compared to controls, each patient group showed a large area of overlapping atrophy in bilateral parietal, occipital, precuneus, posterior cingulate, posterior temporal, and hippocampal regions. Surrounding this common area, group-specific atrophy was found in small, symptom-specific regions for each group: the right ventral-occipital and superior parietal regions in PCA, the left middle and superior temporal gyri in LPA, and the prefrontal cortex in EO-AD. APOE epsilon4 frequency was higher in all patient groups compared to controls. Four PCA, 5 LPA, and 8 EO-AD patients showed evidence of cortical amyloid at pathology (n = 3) or on PIB-PET (n = 14).ConclusionsLogopenic progressive aphasia and posterior cortical atrophy showed largely overlapping anatomic and biologic features with early age at onset of Alzheimer disease, suggesting that these clinical syndromes represent the spectrum of clinical manifestation of the nontypical form of Alzheimer disease that presents at an early age.
| S-EPMC2777069 | biostudies-literature
Project description:BackgroundInterpersonal trauma (IPT) is highly prevalent among HIV-positive (HIV+) individuals, but its relationship with brain morphology and function is poorly understood.SettingThis cross-sectional analysis evaluated the associations of IPT with cognitive task performance, daily functioning, magnetic resonance imaging (MRI) brain cortical thickness, and bilateral volumes of 4 selected basal ganglia regions in a US-based cohort of aviremic HIV+ individuals, with (HIV+ IPT+) and without IPT exposure (HIV+ IPT-), and sociodemographically matched HIV-negative controls with (HIV- IPT+) and without IPT exposure (HIV- IPT-).MethodsEnrollees completed brain MRI scans, a semistructured psychiatric interview, a neurocognitive battery, and 3 measures of daily functioning. Demographic and clinical characteristics of the 4 groups were described, and pairwise between-group comparisons performed using χ tests, analysis of variance, or t-tests. Linear or Poisson regressions evaluated relationships between group status and the outcomes of interest, in 6 pairwise comparisons, using Bonferroni correction for statistical significance.ResultsAmong 187 participants (mean age 50.0 years, 63% male, 64% non-white), 102 were HIV+ IPT+, 35 were HIV+ IPT-, 26 were HIV- IPT-, and 24 were HIV- IPT+. Compared with the remaining 3 groups, the HIV+ IPT+ group had more activities of daily living declines, higher number of impaired Patient's Assessment of Own Functioning Inventory scores, and lower cortical thickness in multiple cerebral regions. Attention/working memory test performances were significantly better in HIV- IPT- compared with the HIV+ IPT+ and HIV+ IPT- groups. Basal ganglia MRI volumes were not significantly different in any between-group comparisons.ConclusionIPT exposure and HIV infection have a synergistic effect on daily functioning and cortical thickness in aviremic HIV+ individuals.
| S-EPMC8376232 | biostudies-literature
Project description:This study investigated the functional brain connectome architecture in patients with Posterior Cortical Atrophy (PCA). Eighteen PCA patients and 29 age- and sex- matched healthy controls were consecutively recruited in a specialized referral center. Participants underwent neurologic examination, cerebrospinal fluid (CSF) examination for Alzheimer's disease (AD) biomarkers, cognitive assessment, and brain MRI. For a smaller subset of participants, FDG-PET examination was available. We assessed topological brain network properties and regional functional connectivity as well as intra- and inter-hemispheric connectivity, using graph analysis and connectomics. Supplementary analyses were performed to explore the association between the CSF AD profile and the connectome status, and taking into account hypometabolic, atrophic, and spared regions (nodes). PCA patients showed diffuse functional connectome alterations at both global and regional level, as well as a connectivity breakdown between the posterior brain nodes. They had a widespread loss of both intra- and inter-hemispheric connections, exceeding the structural damage, and including the frontal connections. In PCA, connectome alterations were identified in all the brain nodes irrespectively of their structural and metabolic classification and were associated with a connectivity breakdown between damaged and spared areas. Taken together, these findings suggest the potentially high sensitivity of graph-analysis and connectomic in capturing the progression and maybe early signs of neurodegeneration in PCA patients.
| S-EPMC6931188 | biostudies-literature
Project description:ObjectiveWe report (1) the quantitative investigation of text reading in posterior cortical atrophy (PCA), and (2) the effects of 2 novel software-based reading aids that result in dramatic improvements in the reading ability of patients with PCA.MethodsReading performance, eye movements, and fixations were assessed in patients with PCA and typical Alzheimer disease and in healthy controls (experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (experiment 2).ResultsMean reading accuracy in patients with PCA was significantly worse (57%) compared with both patients with typical Alzheimer disease (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%-270%) and self-rated measures of reading. Data suggest a greater efficiency of fixations and eye movements under the single-word reading aid in patients with PCA.ConclusionsThese findings demonstrate how neurologic characterization of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities.Classification of evidenceThis study provides Class III evidence that for patients with PCA, 2 software-based reading aids (single-word and double-word) improve reading accuracy.
| S-EPMC4520813 | biostudies-literature
Project description:BackgroundPosterior cortical atrophy (PCA) is typically considered to be a visual syndrome, primarily characterised by progressive impairment of visuoperceptual and visuospatial skills. However, patients commonly describe early difficulties with word retrieval. This paper details the first systematic analysis of linguistic function in PCA. Characterising and quantifying the aphasia associated with PCA is important for clarifying diagnostic and selection criteria for clinical and research studies.Methods15 patients with PCA, seven patients with logopenic/phonological aphasia (LPA) and 18 age matched healthy participants completed a detailed battery of linguistic tests evaluating auditory input processing, repetition and working memory, lexical and grammatical comprehension, single word retrieval and fluency, and spontaneous speech.ResultsRelative to healthy controls, PCA patients exhibited language impairments across all of the domains examined, but with anomia, reduced phonemic fluency and slowed speech rate the most prominent deficits. PCA performance most closely resembled that of LPA patients on tests of auditory input processing, repetition and digit span, but was relatively stronger on tasks of comprehension and spontaneous speech.ConclusionsThe study demonstrates that in addition to the well reported degradation of vision, literacy and numeracy, PCA is characterised by progressive oral language dysfunction with prominent word retrieval difficulties. Overlap in the linguistic profiles of PCA and LPA, which are both most commonly caused by Alzheimer's disease, further emphasises the notion of a phenotypic continuum between typical and atypical manifestations of the disease. Clarifying the boundaries between Alzheimer's disease phenotypes has important implications for diagnosis, clinical trial recruitment and investigations into biological factors driving phenotypic heterogeneity in Alzheimer's disease. Rehabilitation strategies to ameliorate the phonological deficit in PCA are required.
| S-EPMC4667396 | biostudies-literature
Project description:Background/purposeSporadic early-onset Alzheimer disease (sEOAD) and its visual variant, posterior cortical atrophy (PCA), have a disease onset at less than 65 years of age with no familial aggregation. The etiology and genetic basis of these diseases remain poorly understood. Our study aimed to identify additional mutations or variants associated with sEOAD and PCA and to further examine their genetic and phenotypic spectrums.MethodsWe performed whole-exome sequencing and analyzed the clinical and neuroimaging features of mutation carriers with 29 patients having sEOAD and 25 having PCA.ResultsNine rare damaging variants were identified in 4 patients with sEOAD and 3 with PCA. A novel mutation (p.A136V) in PSEN1 was identified in a patient with sEOAD and a likely pathogenic variant (p.M239T) was identified for PSEN2 in a patient with PCA. In addition, 7 rare damaging variants were detected in other genes related to neurodegenerative diseases. The patient carrying the PSEN1 p.A136V mutation presented with typical clinical and imaging features of sEOAD, and the PCA patient with the PSEN2 p.M239T mutation presented with visuospatial impairment as the initial symptom.ConclusionOur study expands the PSEN1 mutation spectrum of sEOAD and highlights the importance of screening PSEN1 and/or PSEN2 mutations in PCA patients.
| S-EPMC8386585 | biostudies-literature
Project description:Early-life education (years of schooling) has been investigated in regards to cognition, health outcomes and mortality. It has been shown to confer cognitive reserve that might lessen the impact of brain pathology and its impact on cognitive and motor functioning in a variety of neurodegenerative diseases and, for instance, to influence electrical activity [Begum, T., Reza, F., Ahmed, I., & Abdullah, J. M. (2014). Influence of education level on design-induced N170 and P300 components of event related potentials in the human brain. J Integr Neurosci, 13(1), 71-88. doi:10.1142/S0219635214500058]. On the other hand, demonstrations of a direct association between education and brain-structural measures have been more equivocal and scant. The current study sought to identify univariate cortical-thickness patterns underlying education and general intelligence after adjusting for age, gender and possible in-scanner movement in 353 individuals aged 40 to 80. We followed up this idea with multivariate analyses as well. For univariate analyses, our analyses yielded no robust associations between education and general intelligence beyond confounding effects of gender, age and extraneous in-scanner movement. A subsequent multivariate analyses showed a relationship between education and regional cortical thickness with a robust pattern of negative as well as positive loadings in several right-sided brain areas, speaking to a subtle but robust distributed effect of education on cortical thickness. Cortical thickness variance that is the residual of this education-related pattern was shown to be positively associated with age and extraneous in-scanner movement. Our study thus presents a complex picture of the association of education with regional cortical thickness: education was associated with a distributed brain-wide pattern of positive as well as negative loadings with unaccounted residuals being larger for older participants. Focal regional associations beyond demographic and age covariates were not identified.
| S-EPMC7094839 | biostudies-literature