Biomedical subjects

Douglas N Greve

Publications and source records attributed to Douglas N Greve.

8 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.

Aged↗

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↗

PubMed2005

Meditation experience is associated with increased cortical thickness.

Previous research indicates that long-term meditation practice is associated with altered resting electroencephalogram patterns, suggestive of long lasting changes in brain activity. We hypothesized that meditation practice might also be associated with changes in the brain's physical structure. Magnetic resonance imaging was used to assess cortical thickness in 20 participants with extensive Insight meditation experience, which involves focused attention to internal experiences. Brain regions associated with attention, interoception and sensory processing were thicker in meditation participants than matched controls, including the prefrontal cortex and right anterior insula. Between-group differences in prefrontal cortical thickness were most pronounced in older participants, suggesting that meditation might offset age-related cortical thinning. Finally, the thickness of two regions correlated with meditation experience. These data provide the first structural evidence for experience-dependent cortical plasticity associated with meditation practice.

Adult↗

PubMed2005

Reproducibility of functional MR imaging: preliminary results of prospective multi-institutional study performed by Biomedical Informatics Research Network.

PURPOSE: To prospectively investigate the factors--including subject, brain hemisphere, study site, field strength, imaging unit vendor, imaging run, and examination visit--affecting the reproducibility of functional magnetic resonance (MR) imaging activations based on a repeated sensory-motor (SM) task. MATERIALS AND METHODS: The institutional review boards of all participating sites approved this HIPAA-compliant study. All subjects gave informed consent. Functional MR imaging data were repeatedly acquired from five healthy men aged 20-29 years who performed the same SM task at 10 sites. Five 1.5-T MR imaging units, four 3.0-T units, and one 4.0-T unit were used. The subjects performed bilateral finger tapping on button boxes with a 3-Hz audio cue and a reversing checkerboard. In a block design, 15-second epochs of alternating baseline and tasks yielded 85 acquisitions per run. Functional MR images were acquired with block-design echo-planar or spiral gradient-echo sequences. Brain activation maps standardized in a unit-sphere for the left and right hemispheres of each subject were constructed. Areas under the receiver operating characteristic curve, intraclass correlation coefficients, multiple regression analysis, and paired Student t tests were used for statistical analyses. RESULTS: Significant factors were subject (P < .005), k-space (P < .005), and field strength (P = .02) for sensitivity and subject (P = .03) and k-space (P = .05) for specificity. At 1.5-T MR imaging, mean sensitivities ranged from 7% to 32% and mean specificities were higher than 99%. At 3.0 T, mean sensitivities and specificities ranged from 42% to 85% and from 96% to 99%, respectively. At 4.0 T, mean sensitivities and specificities ranged from 41% to 73% and from 95% to 99%, respectively. Mean areas under the receiver operating characteristic curve (+/- their standard errors) were 0.77 +/- 0.05 at 1.5 T, 0.90 +/- 0.09 at 3.0 T, and 0.95 +/- 0.02 at 4.0 T, with significant differences between the 1.5- and 3.0-T examinations and between the 1.5- and 4.0-T examinations (P < .01 for both comparisons). Intraclass correlation coefficients ranged from 0.49 to 0.71. CONCLUSION: MR imaging at 3.0- and 4.0-T yielded higher reproducibility across sites and significantly better results than 1.5-T imaging. The effects of subject, k-space, and field strength on examination reproducibility were significant.

Adult↗

PubMed2004

Thinning of the cerebral cortex in aging.

The thickness of the cerebral cortex was measured in 106 non-demented participants ranging in age from 18 to 93 years. For each participant, multiple acquisitions of structural T1-weighted magnetic resonance imaging (MRI) scans were averaged to yield high-resolution, high-contrast data sets. Cortical thickness was estimated as the distance between the gray/white boundary and the outer cortical surface, resulting in a continuous estimate across the cortical mantle. Global thinning was apparent by middle age. Men and women showed a similar degree of global thinning, and did not differ in mean thickness in the younger or older groups. Age-associated differences were widespread but demonstrated a patchwork of regional atrophy and sparing. Examination of subsets of the data from independent samples produced highly similar age-associated patterns of atrophy, suggesting that the specific anatomic patterns within the maps were reliable. Certain results, including prominent atrophy of prefrontal cortex and relative sparing of temporal and parahippocampal cortex, converged with previous findings. Other results were unexpected, such as the finding of prominent atrophy in frontal cortex near primary motor cortex and calcarine cortex near primary visual cortex. These findings demonstrate that cortical thinning occurs by middle age and spans widespread cortical regions that include primary as well as association cortex.

Adolescent↗

PubMed2004

Basal ganglia activity remains elevated after movement in focal hand dystonia.

Although previous studies of focal hand dystonia have detected cortical sensorimotor abnormalities, little is known about the role of the basal ganglia in this disorder. We report here that when focal hand dystonic patients performed finger-tapping tasks, functional magnetic resonance imaging showed persisting elevations of basal ganglia activity after the tasks ended. We posit that inhibitory control of the basal ganglia may be faulty in focal hand dystonia, and that the increases we observe in "resting" activity may mask basal ganglia abnormalities in standard imaging contrast analyses.

Adult↗

PubMed2004

Medial temporal lobe function and structure in mild cognitive impairment.

Functional magnetic resonance imaging (fMRI) was used to study memory-associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow-up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow-up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline.

Aged↗

PubMed2003

Identifying regional activity associated with temporally separated components of working memory using event-related functional MRI.

This study describes the neural circuitry underlying temporally separated components of working memory (WM) performance-stimulus encoding, maintenance of information during a delay, and the response to a probe. While other studies have applied event-related fMRI to separate epochs of WM tasks, this study differs in that it employs a methodology that does not make any a priori assumptions about the shape of the hemodynamic response (HDR). This is important because no one model of the HDR is valid across the range of activated brain regions and stimulus types. Systematic modeling inaccuracies may lead to the misattribution of activity to adjacent events. Twelve healthy subjects performed a numerical version of the Sternberg Item Recognition Paradigm adapted for rapid presentation event-related fMRI. This paradigm emphasized maintenance rather than manipulative WM processes and used a subcapacity WM load. WM trials with different delay lengths were compared to fixation. The HDR of the entire WM trial for each trial type was estimated using a finite impulse response (FIR). Regional activity associated with the Encode, Delay, and Probe epochs was identified using contrasts that were based on the FIR estimates and by examining the HDRs. Each epoch was associated with a distinct but overlapping pattern of regional activity. Activation of the dorsolateral prefrontal cortex, thalamus, and basal ganglia was exclusively associated with the probe. This suggests that frontostriatal neural circuitry participates in selecting an appropriate response based on the contents of WM.

Adult↗