Biomedical subjects

Eric M Reiman

Publications and source records attributed to Eric M Reiman.

At least 19 recordsLinked to original sources

PubMed2026

Dose-dependent white matter changes associated with repetitive head impacts in former American football players.

Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45-74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45-74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen's d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen's d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

American football↗

PubMed2026

Regional ventricular enlargement as an in vivo biomarker of cumulative biomechanical neurodegeneration in former American football players.

INTRODUCTION: Repetitive head impacts (RHIs) have been linked to later life neurodegeneration, yet the in vivo structural correlates of cumulative biomechanical loading remain unclear. We examined whether regional ventricular morphology in former American football players reflects exposure burden and traumatic encephalopathy syndrome (TES) classification. METHODS: Participants included 170 male former football players and 54 age-matched asymptomatic male controls from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Subject-specific manual segmentation quantified lateral ventricle, inferior horn, third ventricle, and fourth ventricle volumes. Group and exposure associations were tested using generalized least squares models. RESULTS: Former players showed larger left inferior lateral ventricle volume than controls, with the largest effects among professional players. Greater cumulative linear and rotational acceleration exposure was associated with enlargement across lateral ventricular and inferior horn regions. DISCUSSION: Regional ventricular enlargement may represent an in vivo marker of cumulative biomechanical loading after RHI exposure.

Humans↗

PubMed2025

The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment.

INTRODUCTION: The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS: We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS: Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION: We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS: The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

Humans↗

PubMed2007

Cognitive performance in older women relative to ApoE-epsilon4 genotype and aerobic fitness.

INTRODUCTION: Apolipoprotein E (ApoE) genotype and aerobic fitness are each associated with cognitive performance in older adults. However, their potentially interactive effects on cognitive performance have not been examined. PURPOSE: The primary purpose of this study was to determine whether ApoE genotype and aerobic fitness interact to uniquely impact memory performance and executive functioning. A secondary purpose was to examine the interactive effects on other measures of cognition to provide a more comprehensive assessment of cognitive abilities across a broad range of functions. METHODS: Community-dwelling, cognitively normal older women (N = 90) provided blood samples to allow for assessment of ApoE genotype, completed cognitive tests, and performed a maximal aerobic fitness test. Primary outcome variables were the auditory verbal learning test (AVLT), the complex figures test (CFT), and the Wisconsin card-sorting task (WCST). Secondary outcome variables were the block design test and the paced auditory serial addition task (PASAT). RESULTS: Regression analyses indicated that aerobic fitness was associated with significantly better performance on measures of the AVLT, the CFT, and the PASAT for the ApoE-epsilon4 homozygotes. CONCLUSION: The preliminary findings from this study support the possibility that aerobic fitness is positively associated with the memory performance of those individuals at most genetic risk for Alzheimer disease.

Aged↗

PubMed2006

Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies.

We report the development and validation of experimental methods, study designs, and analysis software for pooling-based genomewide association (GWA) studies that use high-throughput single-nucleotide-polymorphism (SNP) genotyping microarrays. We first describe a theoretical framework for establishing the effectiveness of pooling genomic DNA as a low-cost alternative to individually genotyping thousands of samples on high-density SNP microarrays. Next, we describe software called "GenePool," which directly analyzes SNP microarray probe intensity data and ranks SNPs by increased likelihood of being genetically associated with a trait or disorder. Finally, we apply these methods to experimental case-control data and demonstrate successful identification of published genetic susceptibility loci for a rare monogenic disease (sudden infant death with dysgenesis of the testes syndrome), a rare complex disease (progressive supranuclear palsy), and a common complex disease (Alzheimer disease) across multiple SNP genotyping platforms. On the basis of these theoretical calculations and their experimental validation, our results suggest that pooling-based GWA studies are a logical first step for determining whether major genetic associations exist in diseases with high heritability.

Alzheimer Disease↗

PubMed2006

Relationships between plasma leptin concentrations and human brain structure: a voxel-based morphometric study.

We have previously demonstrated that obese people have reduced grey matter (GM) in several brain areas, including regions implicated in the regulation of taste (i.e., inferior frontal operculum and postcentral gyrus), reward (i.e., putamen), and behavioural processing (i.e., middle frontal gyrus), compared with their lean counterparts. It is well established that the brain may serve as a direct target for adiposity signals, one of the most important being leptin. We investigated the relationships between fasting plasma leptin concentrations and brain tissue composition in a group of 32 young adult Caucasians (12M/20F, age 32+/-1 years, body fat 29+/-1%, mean+/-S.E.) with normal glucose tolerance by using voxel-based morphometry of magnetic resonance imaging scans. Fasting plasma leptin concentrations were positively correlated with GM volumes of the left cerebellum and left inferior temporal gyrus and negatively associated with GM volumes of the left inferior frontal operculum, left postcentral gyrus, and right putamen (P<0.001, uncorrected for multiple comparisons) after adjustment for sex, percent body fat, age, fasting plasma insulin concentrations (i.e., the major determinants of plasma leptin), and global GM volume (thus allowing for an assessment of regional effects only). This study showed an independent, negative correlation between fasting plasma leptin concentrations, which are increased in obesity, and the volumes of GM in brain areas where obese people have reduced GM compared to their lean counterparts. These relationships may explain some of the abnormalities in brain morphology recently found to be associated with excess body fatness.

Adolescent↗

PubMed2006

Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain.

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer's disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders.

Aged↗

PubMed2006

Impaired platelet mitochondrial activity in Alzheimer's disease and mild cognitive impairment.

Mitochondrial abnormalities are found in Alzheimer's disease (AD), but previous reports have not examined at-risk groups. In subjects with AD, mild cognitive impairment (MCI), and non-demented aged controls, platelet and lymphocyte mitochondria were isolated and analyzed for Complexes I, III, and IV of the electron transport chain. Western blots were used to control for differential enrichment of samples. Results demonstrated significant declines in Complexes III and IV in AD, and a significant decline in Complex IV in MCI. This report confirms mitochondrial deficiencies in AD, extends them to MCI, and suggests they are present at the earliest symptomatic stages of disease.

Aged↗

PubMed2006

Common Kibra alleles are associated with human memory performance.

Human memory is a polygenic trait. We performed a genome-wide screen to identify memory-related gene variants. A genomic locus encoding the brain protein KIBRA was significantly associated with memory performance in three independent, cognitively normal cohorts from Switzerland and the United States. Gene expression studies showed that KIBRA was expressed in memory-related brain structures. Functional magnetic resonance imaging detected KIBRA allele-dependent differences in hippocampal activations during memory retrieval. Evidence from these experiments suggests a role for KIBRA in human memory.

Adolescent↗

PubMed2006

Age- and transgene-related changes in regional cerebral metabolism in PSAPP mice.

In parallel to imaging studies in humans with Alzheimer's disease (AD), we have mapped brain metabolic activity in transgenic mouse models of AD. Our aim in both is to provide new surrogate markers of progression to help clarify disease mechanisms and rapidly screen candidate therapeutics. Since previous findings of preferential reductions in posterior cingulate glucose metabolism may have been confounded by morphological abnormalities in previously studied "PDAPP" transgenic mice, we first assessed hippocampal and callosal anatomy in PSAPP (PS1xAPP) mice, another transgenic mouse model of AD, and found no major abnormalities. We then used fluorodeoxyglucose (FDG) autoradiography in older and younger PSAPP and wildtype mice to assess the functional state of 56 regions-of-interest across group, age and increasing amyloid load. Reductions in FDG uptake in aged transgenic mice, with significant interactions between group and age, were found in retrosplenial cingulate gyrus, found to be metabolically affected in persons affected by or at risk for AD, and in brain regions known to participate with retrosplenial cingulate in networks contributing to spatial learning deficits found in these animals. Like patients with AD, PSAPP mice have age-related metabolic reductions in posterior cingulate cortex, a finding that does not appear to be related to morphological abnormalities. If longitudinal studies support these progressive and preferential reductions in retrosplenial metabolism in PSAPP mice, these reductions could provide an indicator of disease progression, help bridge the gap between human and animal studies of AD, and aid in clarification of disease mechanisms and screening of promising treatments.

Aging↗

PubMed2006

Quantitation of heteroplasmy of mtDNA sequence variants identified in a population of AD patients and controls by array-based resequencing.

The role of mitochondrial dysfunction in the pathogenesis of Alzheimer's disease (AD) has been well documented. Though evidence for the role of mitochondria in AD seems incontrovertible, the impact of mitochondrial DNA (mtDNA) mutations in AD etiology remains controversial. Though mutations in mitochondrially encoded genes have repeatedly been implicated in the pathogenesis of AD, many of these studies have been plagued by lack of replication as well as potential contamination of nuclear-encoded mitochondrial pseudogenes. To assess the role of mtDNA mutations in the pathogenesis of AD, while avoiding the pitfalls of nuclear-encoded mitochondrial pseudogenes encountered in previous investigations and showcasing the benefits of a novel resequencing technology, we sequenced the entire coding region (15,452 bp) of mtDNA from 19 extremely well-characterized AD patients and 18 age-matched, unaffected controls utilizing a new, reliable, high-throughput array-based resequencing technique, the Human MitoChip. High-throughput, array-based DNA resequencing of the entire mtDNA coding region from platelets of 37 subjects revealed the presence of 208 loci displaying a total of 917 sequence variants. There were no statistically significant differences in overall mutational burden between cases and controls, however, 265 independent sites of statistically significant change between cases and controls were identified. Changed sites were found in genes associated with complexes I (30.2%), III (3.0%), IV (33.2%), and V (9.1%) as well as tRNA (10.6%) and rRNA (14.0%). Despite their statistical significance, the subtle nature of the observed changes makes it difficult to determine whether they represent true functional variants involved in AD etiology or merely naturally occurring dissimilarity. Regardless, this study demonstrates the tremendous value of this novel mtDNA resequencing platform, which avoids the pitfalls of erroneously amplifying nuclear-encoded mtDNA pseudogenes, and our proposed analysis paradigm, which utilizes the availability of raw signal intensity values for each of the four potential alleles to facilitate quantitative estimates of mtDNA heteroplasmy. This information provides a potential new target for burgeoning diagnostics and therapeutics that could truly assist those suffering from this devastating disorder.

Alzheimer Disease↗

PubMed2006

Regional network of magnetic resonance imaging gray matter volume in healthy aging.

Healthy aging has been associated with brain volume reductions preferentially affecting the frontal cortex, but also involving other regions. We used a network model of regional covariance, the Scaled Subprofile Model, with magnetic resonance imaging voxel-based morphometry to identify the regional distribution of gray matter associated with aging in 26 healthy adults, 22-77 years old. Scaled Subprofile Model analysis identified a pattern that was highly correlated with age (R2=0.66, P<or=0.0001). Older age was associated with less gray matter in the bilateral frontal, temporal,thalamic, and right cerebellar regions. Gender differences suggested more advanced brain aging in the men. In this healthy adult sample, aging was associated with a regional pattern of gray matter atrophy most prominently involving the frontal and temporal cortices. Scaled Subprofile Model network analysis may aid in the detection and tracking of brain aging and in the evaluation of putative antiaging therapies.

Adult↗

PubMed2006

Arithmetic processing in the brain shaped by cultures.

The universal use of Arabic numbers in mathematics raises a question whether these digits are processed the same way in people speaking various languages, such as Chinese and English, which reflect differences in Eastern and Western cultures. Using functional MRI, we demonstrated a differential cortical representation of numbers between native Chinese and English speakers. Contrasting to native English speakers, who largely employ a language process that relies on the left perisylvian cortices for mental calculation such as a simple addition task, native Chinese speakers, instead, engage a visuo-premotor association network for the same task. Whereas in both groups the inferior parietal cortex was activated by a task for numerical quantity comparison, functional MRI connectivity analyses revealed a functional distinction between Chinese and English groups among the brain networks involved in the task. Our results further indicate that the different biological encoding of numbers may be shaped by visual reading experience during language acquisition and other cultural factors such as mathematics learning strategies and education systems, which cannot be explained completely by the differences in languages per se.

Adult↗

PubMed2006

Network analysis of single-subject fMRI during a finger opposition task.

The analysis of functional magnetic resonance imaging (fMRI) data has typically relied on univariate methods to identify areas of brain activity related to cognitive and behavioral task performance. We investigated the ability of multivariate network analysis using a modified form of principal component analysis, the Scaled Subprofile Model (SSM), applied to single-subject fMRI data to identify patterns of interactions among brain regions over time during an anatomically well-characterized simple motor task. We hypothesized that each subject would exhibit correlated patterns of brain activation in several regions known to participate in the regulation of movement including the contralateral motor cortex and the ipsilateral cerebellum. EPI BOLD images were acquired in six healthy participants as they performed a visually and auditorally paced finger opposition task. SSM analysis was applied to the fMR time series on a single-subject basis. Linear combinations of the major principal components that predicted the expected hemodynamic response to the order of experimental conditions were identified for each participant. These combinations of SSM patterns were highly associated with the expected hemodynamic response, an indicator of local neuronal activity, in each participant (0.84 </= R(2) </= 0.97, all P's < 0.0001). As predicted, the combined pattern in each subject was characterized most prominently by relatively increased activations in contralateral sensorimotor cortex and ipsilateral cerebellum. Additionally, all subjects showed areas of relatively decreased activation in the ipsilateral sensorimotor cortex and contralateral cerebellum. The application of network analysis methods, such as SSM, to single-subject fMRI data can identify patterns of task-specific, functionally interacting brain areas in individual subjects. This approach may help identify individual differences in the task-related functional connectivity, track changes in task-related patterns of activity within or between fMRI sessions, and provide a method to identify individual differences in response to treatment.

Acoustic Stimulation↗

PubMed2006

Nonprogressive transgene-related callosal and hippocampal changes in PDAPP mice.

We have previously shown that homozygous PDAPP mice, a transgenic model of Alzheimer's-like amyloidosis, have abnormal corpus callosi and anterior hippocampi. Now, we investigated the extent to which these morphological abnormalities are correlated with mutant gene dose in a larger, independent, and substantially younger cohort. Homozygous and heterozygous PDAPP mice had significantly smaller callosal commissure length and anterior hippocampal area than controls. Reductions correlated with mutant APP gene dose, with homozygotes showing the greatest reduction, and were present at 2 months of age. These findings and previous work with APP knockouts suggest that PDAPP mice have impaired white matter development due to interference with native murine APP.

Agenesis of Corpus Callosum↗

PubMed2006

Brain abnormalities in human obesity: a voxel-based morphometric study.

Obesity is accompanied by damage to several tissues. Overweight is a risk factor for Alzheimer's disease and other neurodegenerative disorders. Whether structural abnormalities associated with excess body fat may also occur in the brain is unknown. We sought to determine to what extent excess body fat is associated with regional alterations in brain structure using voxel-based morphometry (VBM), a whole-brain unbiased technique based upon high-definition 3D magnetic resonance imaging (MRI) scans normalized into a common standard space and allowing for an objective assessment of neuroanatomical differences throughout the brain. We studied 24 obese (11 male, 13 female; age: 32 +/- 8 years; body mass index [BMI]: 39.4 +/- 4.7 kg/m2) and 36 lean (25 male, 11 female; mean age: 33 +/- 9 years; BMI: 22.7 +/- 2.2 kg/m2) non-diabetic Caucasians. In comparison with the group of lean subjects, the group of obese individuals had significantly lower gray matter density in the post-central gyrus, frontal operculum, putamen, and middle frontal gyrus (P < 0.01 after adjustment for sex, age, handedness, global tissue density, and multiple comparisons). BMI was negatively associated with GM density of the left post-central gyrus in obese but not lean subjects. This study identified structural brain differences in human obesity in several brain areas previously involved in the regulation of taste, reward, and behavioral control. These alterations may either precede obesity, representing a neural marker of increased propensity to gaining weight, or occur as a consequence of obesity, indicating that also the brain is affected by increased adiposity.

Adult↗

PubMed2006

Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity.

BACKGROUND: In an exploratory positron emission tomography study of postprandial regional cerebral blood flow, which is a marker of neuronal activity, obese men differed from lean men in several brain regions, including the prefrontal cortex. The subjects received a meal proportional to their body size; therefore, the meal volume was different for each person. OBJECTIVE: We investigated whether differences in the brain responses of obese and lean men to a meal represent satiety or feelings of gastric distension. DESIGN: We studied 9 lean (x +/- SD body fat: 15 +/- 5%; age: 33 +/- 10 y) and 9 obese (body fat: 31 +/- 4%; age: 32 +/- 10 y) men given a fixed amount (400 mL) of a liquid meal. We compared their results with those in 11 lean (body fat: 16 +/- 5%; age: 35 +/- 8 y) and 11 obese (body fat: 33 +/- 5%; age: 28 +/- 5 y) previously studied men given a meal proportional to their body size. We performed analyses by using a two-level, random-effects approach in the STATISTICAL PARAMETRIC MAPPING software package and a significance level of P < or = 0.001, uncorrected for multiple comparisons. RESULTS: Compared with lean men, obese men had consistently less postprandial activation in the left dorsolateral prefrontal cortex, irrespective of meal size. CONCLUSION: Because the dorsolateral prefrontal cortex has been implicated in the inhibition of inappropriate behavior, satiety, and meal termination, differential responses of neuronal activity to food intake in this area may contribute to a propensity for obesity or to the difficulty in losing weight experienced by obese men.

Adult↗

PubMed2006

A preliminary fluorodeoxyglucose positron emission tomography study in healthy adults reporting dream-enactment behavior.

STUDY OBJECTIVES: To test the hypothesis that healthy adults reporting dream-enactment behavior (DEB+) have reduced cerebral metabolic rate for glucose (CMRgl) in regions preferentially affected in patients with dementia with Lewy bodies (DLB). DESIGN: Automated brain-mapping algorithms were used to compare regional fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements from previously evaluated DEB cases and controls. SETTING: Tertiary-care academic medical centers. PARTICIPANTS: Seventeen cognitively normal patients with DEB+ and 17 control subjects (DEB-) who were individually matched for age (59 +/- 11 years), education level (16 +/- 4 years), sex (67% women), body mass index (26 +/- 4.8 kg/m2), first-degree relative with dementia (85%), and proportion of apolipoprotein E (APOE) e4 carriers (13 e4 carriers, 4 noncarriers). INTERVENTIONS: FDG-PET. MEASUREMENTS AND RESULTS: DEB was associated with significantly lower CMRgl in several brain regions known to be preferentially affected in both DLB and Alzheimer disease (parietal, temporal, and posterior cingulate cortexes) and in several other regions, including the anterior cingulate cortex (p < .001, uncorrected for multiple comparisons). The DEB-associated CMRgl reductions were significantly greater in the APOE e4 noncarriers than in the carriers. CONCLUSIONS: These preliminary findings suggest that cognitively normal persons with DEB have reduced CMRgl in brain regions known to be metabolically affected by DLB, supporting further study of DEB as a possible risk factor for the development of DLB.

Adult↗