Biomedical subjects

James T Becker

Publications and source records attributed to James T Becker.

At least 19 recordsLinked to original sources

PubMed2025

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.

BACKGROUND: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. RESULTS: We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.13 (LHX5-AS1). We additionally identify three population-specific loci with genome-wide significance at/near PTPRK and GRB14 in HIS and KIAA0825 in NHW. Pathway analysis implicates multiple amyloid regulation pathways and the classical complement pathway. Genes at/near our novel loci have known roles in neuronal development (LRRC4C, LHX5-AS1, and PTPRK) and insulin receptor activity regulation (GRB14). CONCLUSIONS: Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for further elucidating the genomics of late-onset Alzheimer's disease.

Humans↗

PubMed2006

3D pattern of brain atrophy in HIV/AIDS visualized using tensor-based morphometry.

UNLABELLED: 35% of HIV-infected patients have cognitive impairment, but the profile of HIV-induced brain damage is still not well understood. Here we used tensor-based morphometry (TBM) to visualize brain deficits and clinical/anatomical correlations in HIV/AIDS. To perform TBM, we developed a new MRI-based analysis technique that uses fluid image warping, and a new alpha-entropy-based information-theoretic measure of image correspondence, called the Jensen-Rényi divergence (JRD). METHODS: 3D T1-weighted brain MRIs of 26 AIDS patients (CDC stage C and/or 3 without HIV-associated dementia; 47.2+/-9.8 years; 25M/1F; CD4+ T-cell count: 299.5+/-175.7/microl; log10 plasma viral load: 2.57+/- 1.28 RNA copies/ml) and 14 HIV-seronegative controls (37.6+/-12.2 years; 8M/6F) were fluidly registered by applying forces throughout each deforming image to maximize the JRD between it and a target image (from a control subject). The 3D fluid registration was regularized using the linearized Cauchy-Navier operator. Fine-scale volumetric differences between diagnostic groups were mapped. Regions were identified where brain atrophy correlated with clinical measures. RESULTS: Severe atrophy ( approximately 15-20% deficit) was detected bilaterally in the primary and association sensorimotor areas. Atrophy of these regions, particularly in the white matter, correlated with cognitive impairment (P = 0.033) and CD4+ T-lymphocyte depletion (P = 0.005). CONCLUSION: TBM facilitates 3D visualization of AIDS neuropathology in living patients scanned with MRI. Severe atrophy in frontoparietal and striatal areas may underlie early cognitive dysfunction in AIDS patients, and may signal the imminent onset of AIDS dementia complex.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Ventricular volume and dementia progression in the Cardiovascular Health Study.

Elevated cerebral ventricular volume may be associated with dementia risk and progression. A fully-automated technique that agreed highly with radiological readings was used to estimate lateral ventricle volume on MR scans done at baseline in 1997-99 of 377 subjects in the Cardiovascular Health Study (CHS) from the Pittsburgh Center. 327 subjects were normal or diagnosed with mild cognitive impairment (MCI) at baseline and were evaluated 4 years later. Baseline ventricular volume was analyzed in multivariate models with age, gender, education level, presence and incidence of cerebral infarcts, and dementia category (normal, MCI, or dementia) at baseline and follow-up as fixed effects. Ventricular volume at baseline was significantly higher among subjects normal at baseline and demented 4 years later. Age, gender, education level, and dementia progression were significant factors affecting ventricular volume. Ventricular volume was higher in dementia compared to MCI, higher in MCI compared to controls, and higher in Possible-Alzheimer's-disease (AD) dementia compared to Probable-AD. Larger ventricles in healthy subjects may indicate susceptibility to, or progression of, dementia-related pathology.

Aged↗

PubMed2006

3D mapping of ventricular and corpus callosum abnormalities in HIV/AIDS.

OBJECTIVE: 40 million people worldwide are now infected with HIV/AIDS, an illness that often leads to rapidly progressing dementia and death. Even so, little is known about how AIDS affects the brain. Using computational anatomy techniques, we mapped how AIDS impacts the corpus callosum (CC) and ventricular system, two systems that show prominent changes on MRI. We (1) identified regions with greatest differences between AIDS patients and healthy controls and (2) correlated specific 3D patterns of structural differences with measures of immune system deterioration and cognitive decline. METHODS: 51 3D brain MRI scans from 30 non-demented AIDS patients (age: 43.4 years +/- 7.6 SD) and 21 HIV-seronegative controls (age: 39.5 years +/- 12.2) were aligned to ICBM standard space. 3D surface mesh reconstructions of the lateral ventricles and CC were spatially averaged and compared across diagnostic groups. Structural alterations were correlated with viral load, T cell counts, and cognitive impairment. RESULTS: Statistical maps revealed the 3D profile of ventricular expansion and callosal thinning in AIDS. Specific 3D ventricular changes were linked with immune system decline (CD4+ T cell counts; P < 0.001) and cognitive impairment (P < 0.009), but not viral load. Frontal horn maps distinguished AIDS patients from controls better than occipital and temporal horn measures. T cell decline linked with callosal thinning in anterior regions connecting frontal areas with greatest cortical atrophy. CONCLUSION: These maps (1) reveal how brain changes in HIV/AIDS relate to immune decline and impaired cognition, and, after further validation and testing, (2) may offer possible neuroimaging markers for anti-viral drug trials, which gauge how well treatments oppose disease progression in the brain.

AIDS Dementia Complex↗

PubMed2006

Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment.

OBJECTIVE: To measure hippocampal volumes in patients diagnosed as having subtypes of mild cognitive impairment (MCI) relative to those of elderly control subjects and those of patients with Alzheimer disease (AD) using 3-dimensional mesh reconstructions. DESIGN: A magnetic resonance imaging volumetric study of MCI subgroups (MCI, amnesic subtype [MCI-A]; and MCI, multiple cognitive domain subtype) using 3-dimensional mesh reconstructions of the structure. SETTING: Referral dementia clinic. SUBJECTS: Twenty-six subjects with MCI (MCI-A, n = 6; and MCI, multiple cognitive domain subtype, n = 20), 20 subjects with AD, and 20 controls who were equivalent in age, education, and sex distributions. MAIN OUTCOME MEASURES: Three-dimensional parametric mesh models of the hippocampus and total hippocampal volumes. RESULTS: The hippocampi of the patients with AD were significantly atrophic relative to those of the healthy controls. The MCI, multiple cognitive domain subtype, group did not differ from the controls, yet was significantly different from the MCI-A and the AD groups. The MCI-A patients had significant hippocampal atrophy compared with the controls, and did not differ significantly from the patients with AD. CONCLUSION: These data add to the growing evidence that there are multiple forms of MCI, that they have distinct neuropathological correlates, and that MCI, multiple cognitive domain subtype, is not a more advanced form of the MCI-A subtype.

Aged↗

PubMed2006

Positron emission tomography imaging of peripheral benzodiazepine receptor binding in human immunodeficiency virus-infected subjects with and without cognitive impairment.

The pathology associated with late-stage dementia in human immunodeficiency virus (HIV) infection has been studied extensively. Neuropathological examination has demonstrated abundant activation and infection of macrophages/microglia termed HIV encephalitis. For obvious reasons, less is known regarding the neuropathology of minor cognitive impairment seen in earlier stages of HIV infection. The authors examined the utility of the peripheral benzodiazepine receptor ligand PK11195 in positron emission tomography (PET) imaging to assess microglial/macrophage activation in the brains of HIV-infected subjects with minor neurocognitive impairment in a cross-sectional study of 12 HIV infected individuals and 5 age-matched noninfected controls. Subjects were given a battery of neuropsychological tests in addition to assessing CD4 T-cell count and peripheral viremia followed by contrast enhanced magnetic resonance imaging (MRI) and PET with [15O]H2O followed by [11C](R)-PK11195. Two of the six neurocognitively impaired HIV-infected subjects demonstrated plasma viral breakthrough, whereas only one of six nonimpaired individuals demonstrated plasma viral load near the limits of detection. MRI demonstrated no abnormal enhancement and although atrophy was more prominent in impaired subjects, it was also present though to a lesser extent in nonimpaired subjects. None of the 12 HIV-infected subjects demonstrated increased retention of [11C](R)-PK11195 in the brain parenchyma compared to the 5 controls. These results suggest that either [11C](R)-PK11195 PET assessment is insensitive to the degree of macrophage activation in HIV-associated minor neurocognitive impairment or macrophage activation is not the pathological substrate of this neurological condition.

AIDS Dementia Complex↗

PubMed2006

Persistence of neuropsychologic deficits in the remitted state of late-life depression.

OBJECTIVE: Cognitive impairment in late-life depression (LLD) is prevalent, disabling, and persists despite the remission of depressive symptoms. This article characterizes neuropsychologic functioning during remission in LLD. METHODS: The authors examined longitudinal performance on a comprehensive neuropsychologic battery in 56 nondemented subjects age 60 or older who initially presented with an episode of nonpsychotic unipolar major depression and 40 nondemented, age- and education-equated comparison subjects with no history of depression. Subjects were assessed at baseline (in a depressed state) and one year later (when remitted). RESULTS: After one year, 45% of the LLD subjects were cognitively impaired despite remission of depression. Visuospatial ability, information-processing speed, and delayed memory were most frequently impaired; 94% of the patients who were impaired at baseline remained impaired one year later. Twenty-three percent of the patients who were cognitively normal while depressed developed impairment one year later. CONCLUSIONS: Most older individuals who are cognitively impaired during a depressive episode remain impaired when their depression remits. In addition, a substantial proportion of older depressed individuals who are cognitively intact when depressed are likely to be impaired one year later, although their depression has remitted.

Age Factors↗

PubMed2005

Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline.

HIV/AIDS infection is the fourth leading cause of death worldwide, and one in every 100 adults aged 15-49 years is HIV-infected. Forty percent of AIDS patients suffer from neurological symptoms, but the selective profile of damage caused by HIV in the brain is not well understood. Here, we report 3D maps revealing how AIDS affects the human cerebral cortex, identifying the most vulnerable regions and where deficits link with cognitive decline and immune-system suppression. With high-resolution brain MRI scans, we created composite maps of cortical gray-matter thickness in 26 AIDS patients and 14 healthy controls to establish the selective pattern of brain deficits in AIDS. In AIDS, primary sensory, motor, and premotor cortices were 15% thinner. Thinner frontopolar and language cortex correlated with immune system deterioration measured through blood levels of CD4+ T lymphocytes. Prefrontal and parietal tissue loss correlated with cognitive/motor deficits. T cell depletion and cognitive impairment are, therefore, associated with specific 3D brain-deficit patterns visualized with MRI. These quantitative MRI-based maps reveal that HIV selectively damages the cortex. They provide an approach to gauge the impact of AIDS on the living brain and show that the brain is still vulnerable to infection even when patients are receiving antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Atlas-based hippocampus segmentation in Alzheimer's disease and mild cognitive impairment.

This study assesses the performance of public-domain automated methodologies for MRI-based segmentation of the hippocampus in elderly subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Structural MR images of 54 age- and gender-matched healthy elderly individuals, subjects with probable AD, and subjects with MCI were collected at the University of Pittsburgh Alzheimer's Disease Research Center. Hippocampi in subject images were automatically segmented by using AIR, SPM, FLIRT, and the fully deformable method of Chen to align the images to the Harvard atlas, MNI atlas, and randomly selected, manually labeled subject images ("cohort atlases"). Mixed-effects statistical models analyzed the effects of side of the brain, disease state, registration method, choice of atlas, and manual tracing protocol on the spatial overlap between automated segmentations and expert manual segmentations. Registration methods that produced higher degrees of geometric deformation produced automated segmentations with higher agreement with manual segmentations. Side of the brain, presence of AD, choice of reference image, and manual tracing protocol were also significant factors contributing to automated segmentation performance. Fully automated techniques can be competitive with human raters on this difficult segmentation task, but a rigorous statistical analysis shows that a variety of methodological factors must be carefully considered to insure that automated methods perform well in practice. The use of fully deformable registration methods, cohort atlases, and user-defined manual tracings are recommended for highest performance in fully automated hippocampus segmentation.

Aged↗

PubMed2005

Differential cortical atrophy in subgroups of mild cognitive impairment.

OBJECTIVE: To compare gray matter brain volumes in patients diagnosed with subtypes of mild cognitive impairment (MCI) (those with a focal amnestic disorder and those with more diffuse cognitive dysfunction) with those of elderly controls. DESIGN: Magnetic resonance imaging volumetric study of MCI subgroups (MCI-amnestic [MCI-A], and MCI-multiple cognitive domain [MCI-MCD]) using a whole brain voxel-based analysis. SETTING: Referral dementia clinic. Patients Thirty-seven patients with MCI (age range, 49-85 years; MCI-A, n = 9; MCI-MCD, n = 28) and 47 control subjects (age range, 55-81 years). MAIN OUTCOME MEASURES: Volumetric anatomical magnetic resonance imaging differences between MCI subgroups and normal controls, and between patients with MCI who progressed to dementia. Magnetic resonance imaging scans were analyzed using statistical software SPM99. RESULTS: Overall, the patients with MCI had significantly decreased volume in the hippocampus and middle temporal gyrus, bilaterally, compared with control subjects. Compared with patients with MCI-MCD, patients with MCI-A had significant volume loss of the left entorhinal cortex and inferior parietal lobe. Compared with patients with MCI-A, patients with MCI-MCD had significantly reduced volume of the right inferior frontal gyrus, right middle temporal gyrus, and bilateral superior temporal gyrus. Patients with MCI who progressed to Alzheimer disease during follow-up (mean interval 2 years, maximum 4.5 years), showed greater atrophy in the left entorhinal cortex, bilateral superior temporal gyri, and right inferior frontal gyrus compared with those who did not progress. CONCLUSIONS: These data provide evidence of distinct brain structural abnormalities in 2 groups of patients with MCI. While both have mesial temporal and cortical volume loss, those with a focal memory deficit have more involvement of the mesial temporal structures and less involvement of the neocortical heteromodal association areas than those patients with MCI with diffuse cognitive dysfunction. Thus, MCI may represent a more heterogeneous group than currently conceived, possibly reflecting 2 different etiological processes to dementia. These data also suggest that these structural abnormalities precede the development of Alzheimer disease.

Aged↗

PubMed2005

Non-cognitive symptoms in mild cognitive impairment subjects.

The term mild cognitive impairment (MCI) is used to identify individuals with worse cognitive performance than those with normal aging, and who are at risk of dementia, especially Alzheimer's disease (AD). Although the MCI concept is based on the presence of specific cognitive deficits, several studies have shown that these subjects can develop depression, disruptive behaviors (e.g., agitation, aggression), and psychosis. In this study, we examined the baseline psychiatric characteristics of 228 MCI (Mean age: 71.2, Mini-mental State Examination [MMSE] score: 25.9) and 427 mildly demented Probable AD (Mean age: 73.2; Mean MMSE score: 23.5) subjects from a referral dementia clinic. The psychiatric assessment was conducted by geriatric psychiatrists using semi-structured interviews. The proportion of subjects with major depression (MCI: 7.5% vs. Probable AD: 8%) and aggression (MCI: 10% vs. Probable AD: 12.5%) was similar in the two groups. There were more Probable AD patients with psychomotor agitation (52% vs. 38%), delusions (29% vs. 14%), and hallucinations (9% vs. 4%) than MCI subjects. Within MCI groups, we did not observe any differences between MCI subjects with amnesic syndrome versus MCI subjects with a much broader cognitive deficit. These results showed that the MCI syndrome is not circumscribed to a neuropsychological definition, but occurs with a wide range of psychiatric syndromes. Furthermore, it is possible that the development of disruptive behaviors and psychosis, in MCI subjects with no previous history of psychiatric illness, constitutes a strong indication that there is an underlying neurodegenerative disorder.

Aged↗

PubMed2005

Alteration of a clinically meaningful outcome in the natural history of Alzheimer's disease by cholinesterase inhibition.

OBJECTIVES: To describe the effect of cholinesterase inhibitors (CEIs) on the natural course of Alzheimer's disease (AD) using clinically meaningful outcomes. DESIGN: Cross-sectional and longitudinal study. SETTING: Referral dementia clinic. PARTICIPANTS: One hundred thirty-five matched pairs of patients with probable AD. MEASUREMENTS: The risk of AD patients being classified as slow progressors (Mini-Mental State Examination (MMSE) score change <or=2 at 1-year follow-up) was examined as a function of treatment with CEIs. A logistic regression analysis, controlling for age, sex, education level, MMSE score, Blessed Dementia Rating Scale (BDRS) for activities of daily living (ADLs), extrapyramidal signs, psychosis, major depression, and use of antidepressants, antipsychotics, and sedative/hypnotics determined the factors that best predict slow progression and nursing home admission. RESULTS: Eighty-one (60%) of the patients on CEIs and 53 (39%) of the patients who never used CEIs were considered slow progressors (P=.001) at 1-year follow-up. Slow progression was associated only with CEI use (relative risk (RR)=2.45, 95% confidence interval (CI)=1.45-4.16), and sedative/hypnotics use was associated with a MMSE change of 3 points or more (RR=0.35, 95% CI=0.13-0.93). CEI use had a protective effect on nursing home admission (RR=0.095, 95% CI=0.03-0.30), whereas higher scores on the BDRS for ADLs increased risk of admission at 24- and 36-month follow-up. CONCLUSION: CEI use had a clinically meaningful effect on the natural history of AD. Patients taking CEIs were 2.5 times more likely to progress slowly and had a lower risk of nursing home admission after 2 years, even after controlling for multiple factors that can alter the course of the disease, and a slower rate of decline during the first year of follow-up.

Aged↗

PubMed2004

Prevalence of cognitive disorders differs as a function of age in HIV virus infection.

OBJECTIVES: Ten per cent of all new cases of AIDS in the United States are in persons older than 50 years. This is particularly problematical in the case of the neuropsychiatric consequences of HIV, because there are neuropsychiatric disorders which become common in older individuals in the absence of HIV. The purpose of this report is to describe the prevalence and incidence of cognitive impairment in HIV-infected individuals enrolled in a community-based study. DESIGN: The study consisted of community-based, sentinel survey physician referrals of HIV-infected patients, with volunteer recruitment of risk-appropriate seronegative controls. One-year longitudinal follow-up study. METHODS: Detailed neuropsychiatric evaluations were performed at study entry and after one year. A brief, interim visit tracked incident change. Each subject's neuropsychological test performance was classified as normal, demented, or cognitive impairment (not demented). RESULTS: The prevalence of cognitive disorder among HIV-positive individuals over 50 years was significantly greater than in individuals younger than 50 years. Among older participants, dementia was the more common classification (23%), whereas among younger participants, a milder form of cognitive impairment was more prevalent (22%). Alcohol abuse/dependence was a significant risk factor for a disorder, whereas greater education was a protective factor. The one-year incidence of disorder in the sample overall was low (7.3%), and age was not a significant risk factor. However, HIV viral load at study entry was significantly higher among those participants who had developed cognitive impairment one year later. CONCLUSION: Age is a significant risk modifier for prevalent neuropsychological disorder.

Activities of Daily Living↗

PubMed2004

Psychiatric and neurocognitive disorders among HIV-positive and negative veterans in care: Veterans Aging Cohort Five-Site Study.

BACKGROUND: The risk for psychiatric and neurocognitive disorders among middle-aged and older individuals with HIV infection has not been well characterized. METHODS: The Veterans Aging Cohort 5-Site Study enrolled 1803 patients (1047 HIV-positive) from VA infectious disease and general medicine clinics from September 2001 to June 2002. A convenience subset of 10 patients from each site (n = 50) was consented for formal neurocognitive and psychiatric (NCP) testing. Data from this subset were linked to the larger sample. RESULTS: Kappa scores for agreement beyond chance were fair for available measures when compared with formal NCP testing. Using available measures, depressive symptoms (PHQ-9 and provider reported), alcohol abuse or dependence (ICD-9 codes), and drug abuse or dependence (DAST-10) decreased with age in HIV-negative subjects (P trend <0.05) but did not among HIV-positive subjects (P > 0.05). HIV-positive subjects demonstrated higher prevalence of these conditions with increasing age when compared to HIV-negative subjects. Patient report of memory problems increased with age among both groups after excluding those reporting symptoms of depression (PHQ-9e > or = 10). CONCLUSION: Available measures were no substitute for formal NCP testing. Older HIV-positive veterans demonstrate greater prevalence of depressive symptoms, alcohol abuse or dependence, and drug abuse or dependence than age-matched, HIV-negative veterans. Both groups reported increased memory problems with advancing age. This preliminary work suggests a substantial prevalence of psychiatric and neurocognitive problems among middle-aged and older HIV-infected individuals.

Adult↗

PubMed2004

The nature and determinants of neuropsychological functioning in late-life depression.

CONTEXT: Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome. OBJECTIVES: To determine the characteristics and determinants of neuropsychological functioning LLD. DESIGN: Cross-sectional study of groups of LLD patients and control subjects. SETTING: Outpatient, university-based depression research clinic. PARTICIPANTS: One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects. MAIN OUTCOME MEASURES: A comprehensive neuropsychological battery. RESULTS: Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing (beta =.45-.80). Education (beta =.32) and ventricular atrophy (beta =.28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain. CONCLUSIONS: Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.

Age Factors↗

PubMed2004

Diagnosis, risk factors, and treatment of vascular dementia.

Although the introduction of modern neuroimaging techniques and standardized clinical evaluations has improved the identification of cerebrovascular disease, the clinical diagnosis of vascular dementia (VaD) is still problematic. Neuropathologic studies have found the current clinical criteria for VaD had low sensitivity with high specificity, suggesting that cerebrovascular disease of sufficient severity to cause cognitive deficits is frequently associated with other disease processes (eg, Alzheimer's disease). The critical factors about the diagnosis of VaD are centered on two issues: definition of dementia and determination of vascular disease. The current clinical criteria for VaD have different definitions of dementia, which are mainly based on an Alzheimer's disease-like presentation, and severe vascular disease can present with or without history of clinical strokes. Therefore, there is a need for a better definition of VaD. This is extremely important to better understand its risk factors, as well as to create homogenous cohorts suitable for drug trials.

Dementia, Vascular↗

PubMed2004

Functional dissociations within the inferior parietal cortex in verbal working memory.

Neuroimaging studies of working memory have revealed two sites in the left supramarginal gyrus that may support the short-term storage of phonological information. Activation in the left dorsal aspect of the inferior parietal cortex (DIPC) has been observed in contrasts of working memory load, whereas activation in the ventral aspect of the inferior parietal cortex (VIPC) has been found primarily in contrast of information type (verbal vs. nonverbal). Our goal was to determine whether these two areas are functionally distinct or if instead they are part of a homogeneous region with large variations in the focus of peak activity. Toward this end, we used fMRI to assess the neural response in two working memory tasks (N-back and item recognition) in which we also manipulated memory load and the type of information to be recalled (verbal vs. nonverbal). We found both DIPC and VIPC activation in the same group of subjects and further demonstrated that they have differential sensitivity to our experimental factors. Only the DIPC showed robust load effects, whereas only the VIPC showed reliable effects of information type. These results help to account for the differences observed in between-subject comparisons, and they indicate that the two regions are functionally dissociable. In contrast to the DIPC, activity of the VIPC was also recruited in the fixation and low-load conditions, a surprising result that has not been fully explored in prior studies. Despite their distinctive patterns of performance, neither of these regions displayed a pattern of activity that entirely corresponds to common assumptions of a dedicated phonological short-term store (STS). Instead, we hypothesize that the DIPC may support domain-general executive processes, while the VIPC may support phonological encoding-recoding processes central to a variety of language tasks.

Adult↗

PubMed2004

Normative data for determining significance of test-retest differences on eight common neuropsychological instruments.

Clinicians and researchers who use neuropsychological tests to track functioning over time are in need of a method to correct for the effects of practice. Drawing from a large database of healthy, male subjects, we present data that can be used to calculate predicted retest scores for eight widely used neuropsychological instruments either via simple regression or reliable change index (RCI) methods. These methods are useful for individuals assessed across a wide time interval, 4-24 months. Limitations are discussed regarding the applicability of the data. Those with a need to factor out the effects of practice, test-retest reliability and other statistical confounds will find the information within this article useful.

Adult↗