Biomedical subjects

Adam M Brickman

Publications and source records attributed to Adam M Brickman.

At least 19 recordsLinked to original sources

PubMed2026

A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations.

Previously derived polygenic risk scores (PRSs) for Alzheimer's disease (AD) perform inconsistently across diverse ancestries. We developed an APOE-independent multiancestry AD PRS using genome-wide association study summary statistics applied to European ancestry, African American, Caribbean Hispanic and East Asian cohorts. PRS performance was evaluated in a large independent multiancestry dataset and validated in several additional multiancestry cohorts. The PRS was significantly associated with AD in European ancestry, African American, Caribbean Hispanic and Native American Hispanic groups with adjusted odds ratios between 1.14 and 1.52 per PRS standard deviation. PRS performance was validated in the replication cohorts (odds ratios: 1.21-1.65). The PRS was also associated with poorer memory, executive function and language performance, greater AD-related neuropathological burden, reduced hippocampal volume, lower cerebrospinal fluid amyloid-β42 and elevated total tau and phosphorylated tau, with stronger phosphorylated tau associations observed in women. Our findings support the value of ancestry-aware PRSs as a component of broader multimodal risk stratification frameworks.

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PubMed2025

A multi-ancestry polygenic risk score for Alzheimer disease is associated with cognitive decline, hippocampal atrophy and neuropathological hallmarks in diverse populations.

Alzheimer disease (AD) has a strong genetic basis, yet previously derived polygenic risk scores (PRS) are heavily weighted by the APOE locus and perform inconsistently across diverse ancestries. We developed an APOE-independent multi-ancestry AD PRS using genome-wide association study summary statistics from cohorts in the United States, Europe and East Asia that were applied to European ancestry (EA), African American (AA), Caribbean Hispanic (CH), and East Asian cohorts from the Alzheimer's Disease Genetics Consortium. PRS performance was evaluated in the multi-ancestry Alzheimer's Disease Sequencing Project (ADSP) dataset and validated in several additional multi-ancestry cohorts. The PRS was significantly associated with AD in the ADSP EA, AA, CH, and Native American Hispanic groups with adjusted odds ratios (ORs) between 1.14 and 1.52 per standard deviation of the PRS. PRS performance was validated in the replication cohorts (ORs 1.21-1.65). The PRS was also associated with poorer memory, executive function, and language performance; greater AD-related neuropathological burden (including CERAD, Braak stage, and Thal phase scores); reduced hippocampal volume; lower CSF Aβ42; and elevated total tau and phosphorylated tau (p-tau), with stronger p-tau associations observed in women. Longitudinal analyses revealed that individuals in the highest PRS decile exhibited the steepest cognitive decline, particularly among those who progressed to AD. Our findings demonstrate the utility of an ancestry-aware and APOE-independent PRS for advancing understanding of the genetic basis of AD across diverse populations. Associations observed with early biological and cognitive changes and potential sex-specific differences support the incorporation of a PRS in clinical trials and personalized intervention and prevention strategies.

Journal Article↗

PubMed2006

Diffusion tensor imaging of frontal lobe white matter tracts in schizophrenia.

We acquired diffusion tensor and structural MRI images on 103 patients with schizophrenia and 41 age-matched normal controls. The vector data was used to trace tracts from a region of interest in the anterior limb of the internal capsule to the prefrontal cortex. Patients with schizophrenia had tract paths that were significantly shorter in length from the center of internal capsule to prefrontal white matter. These tracts, the anterior thalamic radiations, are important in frontal-striatal-thalamic pathways. These results are consistent with findings of smaller size of the anterior limb of the internal capsule in patients with schizophrenia, diffusion tensor anisotropy decreases in frontal white matter in schizophrenia and hypothesized disruption of the frontal-striatal-thalamic pathway system.

Journal Article↗

PubMed2006

White matter fractional anisotropy and outcome in schizophrenia.

OBJECTIVE: Disparate white matter fractional anisotropy (FA) findings have been reported in patients with schizophrenia in recent years. This may in part reflect heterogeneity of subjects in the studies, including differences in outcome and severity of the illness. We examined whether there is a relationship between white matter FA and outcome in patients with schizophrenia. METHOD: Diffusion-tensor images were obtained in 41 normal subjects and 104 patients with schizophrenia, divided into good-outcome (n=51) and poor-outcome (Kraepelinian; n=53) subtypes based on their ability for self-care. White matter FA and its relationship to regional tissue volumes were evaluated across 40 individual Brodmann's areas using a semi-automated parcellation technique. RESULTS: Overall white matter FA was lower in schizophrenia patients than normal subjects, with regional reductions in widespread temporoparietal and selected prefrontal white matter regions. In schizophrenia patients, lower regional white matter FA was associated with lower regional gray matter volumes. In comparison to normal subjects, overall white matter FA was reduced in patients with poor outcomes in both hemispheres, but to a lesser extent and only in the right hemisphere in good-outcome patients. Lower regional FA was associated with larger regional white matter volumes in good-outcome group. CONCLUSIONS: Global FA reductions implicate white matter as tissue type in the pathophysiology of schizophrenia. In contrast to poor outcome, good outcome in schizophrenia patients may be associated with less extensive FA reductions, higher FA in regional frontal and cingulate white matter, and correlated increases in regional white matter volumes, particularly in the left hemisphere.

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PubMed2006

Regional white matter and neuropsychological functioning across the adult lifespan.

BACKGROUND: The current study utilized magnetic resonance imaging (MRI) to more fully elucidate the relationship among age, regional white matter, and neuropsychological functioning. METHODS: One hundred ninety-nine neurologically healthy adults received MRI and standardized neuropsychological assessment. MR images were spatially normalized and segmented by tissue type; relative white matter values in each of the four cerebral lobes in each hemisphere were computed. Subjects were divided into Younger (ages 21-30), Middle (ages 31-54), and Older (ages 55-79) age groups. RESULTS: The Older group had significantly less overall relative white matter than the Middle group, who had significantly less overall relative white matter than the Younger participants (F (2, 193) = 5.42, p = 0.005). Differences in frontal lobe white matter were of largest magnitude, followed by temporal lobe (F (6, 579) = 3.32, p = 0.003). Age and frontal and temporal lobe white matter were primarily associated with performance on neuropsychological tests of executive functioning and memory. Mediational analysis suggested that frontal lobe white matter mediated the relationship between age and performance on tasks of executive functioning and memory. CONCLUSIONS: The results confirm age-associated decline in frontal and temporal white matter, and age-related cognitive decline in several domains. Decline in neuropsychological functioning is, in part, mediated by a relative age-related reduction in frontal white matter.

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PubMed2006

Structural MRI covariance patterns associated with normal aging and neuropsychological functioning.

Structural magnetic resonance imaging (MRI) studies have shown dramatic age-associated changes in grey and white matter volume, but typically use univariate analyses that do not explicitly test the interrelationship among brain regions. The current study used a multivariate approach to identify covariance patterns of grey and white matter tissue density to distinguish older from younger adults. A second aim was to examine whether the expression of the age-associated covariance topographies is related to performance on cognitive tests affected by normal aging. Eighty-four young (mean age=24.0) and 29 older (mean age=73.1) participants were scanned with a 1.5T MRI machine and assessed with a cognitive battery. Images were spatially normalized and segmented to produce grey and white matter density maps. A multivariate technique, based on the subprofile scaling model, was used to capture sources of between- and within-group variation to produce a linear combination of principal components that represented a "pattern" or "network" that best discriminated between the two age groups. Univariate analyses were also conducted with statistical parametric maps. Grey and white matter covariance patterns were identified that reliably discriminated between the groups with greater than 0.90 sensitivity and specificity. The identified patterns were similar for the univariate and multivariate techniques, and involved widespread regions of the cortex and subcortex. Age and the expression of both patterns were significantly associated with performance on tests of attention, language, memory, and executive functioning. The results suggest that identifiable networks of grey and white matter regions systematically decline with age and that pattern expression is linked to age-related cognitive decline.

Adult↗

PubMed2006

The progression of cognition, psychiatric symptoms, and functional abilities in dementia with Lewy bodies and Alzheimer disease.

BACKGROUND: Although dementia with Lewy bodies (DLB) may be one of most common forms of dementia, relatively little is known about its cognitive and functional course. OBJECTIVE: To compare change over time in general cognitive status, memory test performance, psychiatric symptoms, neurological signs, and functional abilities in patients with probable DLB and probable Alzheimer disease (AD). DESIGN: Twenty-eight patients who met diagnostic criteria for DLB were recruited into the study from 3 sites. Patients with AD (n = 55) were selected from a larger cohort and matched 2 to 1 to the patients with DLB on age and baseline global cognitive status. Patients were followed up at 6-month intervals for an average of 6.2 visits and assessed at each visit with tests of global cognitive functioning and verbal learning and memory and measures of psychiatric, neurological, and functional status. RESULTS: At the baseline evaluation, patients with DLB performed more poorly on a measure of constructional praxis and all measures of functional status. They also had more severe psychiatric symptoms and neurological signs than the AD group. Despite these initial differences, generalized estimating equations applied to regression analyses with repeated measures determined that the only difference between the 2 groups in change in cognitive test performance was on a measure of recognition memory; patients with AD declined, while patients with DLB remained relatively stable. Patients with DLB had relatively stable behavioral symptoms and visual illusions, whereas patients with AD had a significant increase in these symptoms over time. Neurological and functional changes over time were similar in the 2 groups. CONCLUSIONS: Both baseline and longitudinal differences between patients with DLB and patients with AD were noted; these have implications for clinical diagnosis and treatment.

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PubMed2006

Cognitive status of young and older cigarette smokers: data from the international brain database.

Previous studies that have examined the impact of cigarette smoking on cognition have revealed mixed results; some studies report no impact and others report detrimental effects, especially in older individuals. Few studies, however, have examined the effects of cigarette smoking on both young and old healthy individuals using highly robust and standardized methods of cognitive assessment. This study draws on an international database to contrast cognitive differences between younger and older individuals who regularly smoke cigarettes and non-smokers. Data were sampled from 1000 highly screened healthy individuals free of medical or psychiatric health complications. A cohort of 62 regular smokers (n = 45 < 45 years of age; n = 1745 years) with a Fagerstrom nicotine dependency score of 1 or more were identified and matched to a cohort of 62 healthy nonsmokers (n = 43 < 45 years; n = 1945 years) on demographic variables and estimated intelligence. Performances on cognitive measures of attention, reaction time, cognitive flexibility, psychomotor speed, and memory were considered for analysis. As a group, smokers performed more poorly than nonsmokers on one measure of executive function. A significant age and smoking status interaction was identified with older smokers performing more poorly than older nonsmokers and younger smokers on a measure of long-delayed recall of new information. Cigarette smoking is associated with isolated and subtle cognitive difficulties among very healthy individuals.

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PubMed2006

The relationship between frontal gray matter volume and cognition varies across the healthy adult lifespan.

OBJECTIVE: Age-associated decline in gray matter brain volume and cognitive function in healthy adults has been reported in the literature. The goal of the current study is to examine the relationship between age-related changes in regional gray matter volumes and cognitive function in a large, cross-sectional sample of healthy adults across the lifespan. METHODS: Magnetic resonance imaging and cognitive assessment were conducted on 148 adults aged 21-76 years. Multiple regression analyses examining the effect of age were performed on magnetic resonance image-derived gray matter brain volumes and standardized cognitive summary scores of attention and executive function. Regression was also performed to test the effect of age, gray matter volumes, and their interaction on the prediction of cognitive performance. RESULTS: Age significantly predicted performance on tests of attention (F [1, 146]=50.97, p <0.01, R2=0.26) and executive function (F [1, 146]=126.19, p <0.01, R2=0.46) and gray matter volumes for frontal subregions (lateral, medial, orbital), hippocampus, amygdala, and putamen (F [2, 145]=45.34-23.96, p <0.01-0.02). Lateral frontal (beta=-1.53, t=-2.16, df=131, p <0.03) and orbital frontal (beta=1.24, t=2.08, df=131, p <0.04) regions significantly predicted performance on tests of attention. Lateral frontal (beta=-1.69, t=-2.83, df=131, p <0.01) and the interaction between age and lateral frontal volume (beta=3.76, t=2.49, df=131, p <0.02) significantly predicted executive function. CONCLUSIONS: The findings confirm age-associated decline in cognitive function and gray matter volumes, particularly in anterior cortical brain regions. Furthermore, the association between lateral frontal gray matter volume and the ability to successfully plan, organize, and execute strategies varies as a function of age across the healthy adult lifespan.

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PubMed2006

Internal capsule size in good-outcome and poor-outcome schizophrenia.

Converging lines of research suggest that white matter abnormalities may be central to the pathophysiology of schizophrenia. The purpose of this study was to examine regional white matter in the anterior limb of the internal capsules in patients with schizophrenia. The authors obtained high-resolution magnetic resonance imaging in 106 patients with schizophrenia and 42 age and sex-matched healthy comparison subjects. The area of the anterior limb of the internal capsule was measured at five proportionately spaced dorsal-to-ventral levels. Schizophrenia patients were divided into good-outcome and poor-outcome groups, based on longitudinal analysis of self-care deficits. Patients with poor-outcome had significantly smaller dorsal areas than healthy comparison subjects, but good-outcome patients did not differ from healthy comparison subjects. Larger relative volumes of the caudate, putamen, and thalamus tended to be associated with relatively larger volumes of the internal capsule in healthy comparison subjects and good-outcome patients, consistent with the known frontal-striatal-thalamic pathways. Larger ventricles were associated with smaller internal capsules, particularly in healthy comparison subjects. The findings suggest disruption of internal capsule fibers in poor-outcome patients with schizophrenia. These abnormalities may be independent of other structural changes in schizophrenia.

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PubMed2006

Patterns of cognitive performance in middle-aged and older adults: A cluster analytic examination.

Cognitive decline in speeded abilities, executive function, and memory is believed to typify normal aging. However, there is significant variability in cognitive function with advanced age and some reports of relatively intact cognitive function among a subset of older individuals. The present study consists of a cluster analysis to examine the patterns of cognitive function in middle-aged and older individuals. Analyses revealed 3 clusters of middle-aged adults, including an intact group, persons with poor motor speed, and a group with reduced executive function. Three clusters were also identified for older adults, including a group with poor executive function, persons with reduced speed performance (attention, executive function, motor), and a group with global cognitive decline. No evidence emerged for a cluster of older adults with intact performance in all domains or with isolated memory deficits. Findings generally support the frontal aging hypothesis and may provide important information about healthy cognitive aging.

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PubMed2006

Ethical issues in cross-cultural neuropsychology.

Clinical neuropsychologists who assess patients from diverse cultural and linguistic backgrounds face unique ethical challenges. In this article, we address 4 critical questions relevant to ethics of cross-cultural neuropsychology: (a) Should culture or race be considered in neuropsychological testing? (b) Should race- and ethnicity-specific normative data be used in the clinical neuropsychological evaluation? (c) Who is competent to design and translate tests for ethnic minority groups and non-English speakers and who is competent to administer and interpret them? and (d) Are neuropsychology training programs adequately preparing clinicians to be competent in the assessment of cross-cultural groups? The overall aims of the article are to highlight the complexity of these clinical and ethical issues, to provide comprehensive and balanced information to help guide clinician choices, and to stimulate future research in this area.

Cross-Cultural Comparison↗

PubMed2005

Cortical intercorrelations of frontal area volumes in schizophrenia.

BACKGROUND: Abnormal regional volume intercorrelations between selected cortical areas in schizophrenia patients were previously reported in several MRI studies. METHODS: A detailed analysis of frontal gray and white matter volume correlations with Brodmann's area volumes in the rest of the cortex was undertaken in normal subjects (n = 42) and patients with schizophrenia (n = 106), divided into good-outcome (n = 52) and poor-outcome (Kraepelinian; n = 54) subtypes. RESULTS: Frontal gray matter volumes were correlated with temporal lobe volumes in schizophrenics but not in normal subjects. Some frontal-parietal and frontal-occipital correlations showed a similar pattern. In comparison to normal subjects, schizophrenia patients showed weaker or absent intercorrelations intrafrontally, specifically between left motor-premotor and eye-movement areas (4, 6, 8) and dorsolateral area 44, as well as between left areas 9 and 46 vs. area 24 (cingulate gyrus). Poor outcome among patients with schizophrenia was associated with weaker correlations between left frontal area 9 and both medial and lateral temporal cortices, as compared to normal subjects or good-outcome patients. CONCLUSIONS: There appears to be a structural component in the task or symptom-related dysfunctional interactions between the frontal and more posterior cortical regions with preferential pathological involvement of frontotemporal and more limited involvement of frontoparietal and fronto-occipital systems in schizophrenia. Impaired regional associations within the frontal lobe, between left motor-premotor and Broca's areas, may play a role in language processing deficits in schizophrenia, while frontocingulate disconnection may result in working memory disturbances. Poor outcome may be associated with more widespread disconnections between prefrontal vs. cingulate and temporal regions in the left hemisphere, consistent with a disruption along the course of the left cingulum or uncinate bundles.

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PubMed2005

Cortical intercorrelations of temporal area volumes in schizophrenia.

BACKGROUND: Abnormal temporal connections with other cortical areas may underlie some of the most prominent cognitive deficits described in schizophrenia. In order to evaluate the relationship between temporal and other cortical regions in schizophrenia, we examined the intercorrelations of volumetric measures of gray and white matter for each Brodmann's area of the temporal lobe with volumes in the rest of the cortex in patients with schizophrenia and normal comparison subjects. METHODS: MR images were acquired in normal subjects (n=46) and patients with schizophrenia (n=106), divided into good-outcome (n=52) and poor-outcome (Kraepelinian; n=54) subtypes; and correlational patterns between the volumes of individual Brodmann's areas were compared and examined in relation to outcome. RESULTS: Positive frontotemporal intercorrelations were significantly stronger while negative frontotemporal intercorrelations were weaker in schizophrenia patients as compared to normal subjects. Correlations between the right temporal pole and other temporal regions were significantly weaker in schizophrenia patients than in controls. When compared to normal controls and good-outcome patients, schizophrenia patients with poor outcomes showed a selective pattern of stronger gray matter correlations between the medial temporal vs. primary visual and between primary auditory vs. dorsolateral prefrontal cortices, all in the left hemisphere. CONCLUSIONS: Strengthening of positive associations among the temporal and extratemporal (mainly frontal and occipital) regions as well as weakening of regional intercorrelations within the temporal lobe in patients appear to constitute the major differences of correlational patterns in schizophrenia patients and normal subjects. Present findings may be implicated in object recognition deficits seen in patients with schizophrenia, as well as in purportedly deficient spatial and semantic processing of both auditory and visual information that may be associated with poor outcome.

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PubMed2005

Neuroimaging and cardiac correlates of cognitive function among patients with cardiac disease.

In the present study, we examined the relationships between whole brain volume (WBV), subcortical hyperintensities (SH), indices of cardiac disease and cognitive function in nondemented cardiac patients with evidence of mild cerebrovascular disease. A total of 27 individuals with evidence of cardiac disease underwent neuropsychological examination, neuroimaging, and cardiac assessment. Cognition was assessed with the Dementia Rating Scale-2 (DRS). WBV and SH were quantified using a semi-automated thresholding program based on MRI. Correlational analyses revealed that WBV predicted performance on the overall DRS score, the attention subscale and the initiation/perseveration scale. SH were significantly associated with performance on the attention subscale, and the initiation/perseveration subscale. Regression analyses revealed that SH accounted for most of the variance in the initiation/perseveration scale, whereas WBV accounted for most of the variance in the attention scale. The only cardiac structural or functional variable related to the neurological indices was aortic diameter, which was strongly related to both neuroimaging variables, as well as performances on the DRS attention and initiation/perseveration subscales. Our results highlight the importance of overall brain parenchyma in determining cognitive status among patients at risk for cognitive decline and suggest that select indices of structural cardiac morphology may be related to the early phases of cerebrovascular disease and cognitive status.

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PubMed2005

Volume of the cingulate and outcome in schizophrenia.

BACKGROUND: Previous studies indicated that schizophrenia patients have reduced frontal volumes in comparison with normal, but among schizophrenics, reduced volumes of the posterior (temporal, parietal and occipital) cortex were associated with poor outcome. We examined whether this pattern is seen within the anteroposterior arch of the cingulate gyrus. METHODS: MR images were acquired in 37 schizophrenia patients (Kraepelinian, n = 13; non-Kraepelinian, n = 24) and 37 controls, and CSF, gray and white matter volumes in individual Brodmann's areas (BA) of the cingulate arch (areas 25, 24, 23, 31, 30, 29) were assessed and examined in relation to outcome. RESULTS: Schizophrenia patients had significant gray matter reductions in the absolute (mm(3)) volume of Brodmann's area 24 in anterior cingulate and, when corrected for brain size, in the whole cingulate and retrosplenial (areas 29-30) cortex. White matter volumes were increased in right posterior cingulate (area 31). Schizophrenia patients also showed abnormal lateralization of white matter volumes in retrosplenial cortex (area 30) and had lower correlations between frontal and anterior cingulate regions than controls. Poor-outcome subgroup exhibited significant bilateral gray matter deficits in posterior cingulate and retrosplenial cortices compared to good-outcome patients, while no white matter increases in these areas were seen. CONCLUSIONS: Poor outcome was associated with gray matter deficits in posterior cingulate while compensatory white matter increases in dorsal posterior regions may be related to better outcome. Possible consequences of this may include thought disorder, disturbance of consciousness, treatment resistance, and cognitive decline indicative of a dementing process as a superimposed or inherent part of this schizophrenia subtype.

Adult↗

PubMed2005

Progressive morphometric and cognitive changes in vascular dementia.

Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.

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PubMed2005

Category and letter verbal fluency across the adult lifespan: relationship to EEG theta power.

The purpose of this study was to examine the impact of age, sex, and education on category and letter verbal fluency task performance. A secondary goal was to examine whether resting EEG theta power in bilateral frontal and temporal lobes impacts age-associated decline in verbal fluency task performance. A large sample (N = 471) of healthy, normal participants, age 21-82, was assessed for letter fluency (i.e., FAS), and for category fluency (i.e., Animal Naming), and with a 32-channel EEG system for 'eyes-open' resting theta power. The effects of age, sex, and education were examined using analyses of variance. Correlation analyses were used to test the impact of theta power on age and fluency performance by controlling for the effects of theta when examining the relationship between the other two variables. The results indicated that performance on both fluency tests declined linearly with age, but that the rate of decline was greater for category fluency. These age changes were not associated with education level, and there were no sex differences. While theta power was negatively associated with age and positively associated with Animal Naming performance, it did not moderate the relationship between the two. The differential age-associated decline between category and letter fluency suggests separate neurobiological substrates underlying the two domains of performance, which is not related to theta activity.

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