Biomedical subjects

Paul Crane

Publications and source records attributed to Paul Crane.

7 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↗

PubMed2024

X-chromosome-wide association study for Alzheimer's disease.

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

Humans↗

PubMed2006

Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older.

BACKGROUND: Alzheimer disease and other dementing disorders are major sources of morbidity and mortality in aging societies. Proven strategies to delay onset or reduce risk for dementing disorders would be greatly beneficial. OBJECTIVE: To determine whether regular exercise is associated with a reduced risk for dementia and Alzheimer disease. DESIGN: Prospective cohort study. SETTING: Group Health Cooperative, Seattle, Washington. PARTICIPANTS: 1740 persons older than age 65 years without cognitive impairment who scored above the 25th percentile on the Cognitive Ability Screening Instrument (CASI) in the Adult Changes in Thought study and who were followed biennially to identify incident dementia. MEASUREMENTS: Baseline measurements, including exercise frequency, cognitive function, physical function, depression, health conditions, lifestyle characteristics, and other potential risk factors for dementia (for example, apolipoprotein E epsilon4); biennial assessment for dementia. RESULTS: During a mean follow-up of 6.2 years (SD, 2.0), 158 participants developed dementia (107 developed Alzheimer disease). The incidence rate of dementia was 13.0 per 1000 person-years for participants who exercised 3 or more times per week compared with 19.7 per 1000 person-years for those who exercised fewer than 3 times per week. The age- and sex-adjusted hazard ratio of dementia was 0.62 (95% CI, 0.44 to 0.86; P = 0.004). The interaction between exercise and performance-based physical function was statistically significant (P = 0.013). The risk reduction associated with exercise was greater in those with lower performance levels. Similar results were observed in analyses restricted to participants with incident Alzheimer disease. LIMITATIONS: Exercise was measured by self-reported frequency. The study population had a relatively high proportion of regular exercisers at baseline. CONCLUSION: These results suggest that regular exercise is associated with a delay in onset of dementia and Alzheimer disease, further supporting its value for elderly persons.

Age of Onset↗

PubMed2005

Chronic spinal pain and physical-mental comorbidity in the United States: results from the national comorbidity survey replication.

This paper investigates comorbidity between chronic back and neck pain and other physical and mental disorders in the US population, and assesses the contributions of chronic spinal pain and comorbid conditions to role disability. A probability sample of US adults (n=5692) was interviewed. Chronic spinal pain, other chronic pain conditions and selected chronic physical conditions were ascertained by self-report. Mood, anxiety and substance use disorders were ascertained with the Composite International Diagnostic Interview (CIDI). Role disability was assessed with questions about days out of role and with impaired role functioning. The 1 year prevalence of chronic spinal pain was 19.0%. The vast majority (87.1%) of people with chronic spinal pain reported at least one other comorbid condition, including other chronic pain conditions (68.6%), chronic physical conditions (55.3%), and mental disorders (35.0%). Anxiety disorders showed as strong an association with chronic spinal pain as did mood disorders. Common conditions not significantly comorbid with chronic spinal pain were diabetes, heart disease, cancer, and drug abuse. Chronic spinal pain was significantly associated with role disability after controlling for demographic variables and for comorbidities. However, comorbid conditions explained about one-third of the gross association of chronic spinal pain with role disability. We conclude that chronic spinal pain is highly comorbid with other pain conditions, chronic diseases, and mental disorders, and that comorbidity plays a significant role in role disability associated with chronic spinal pain. The societal burdens of chronic spinal pain need to be understood and managed within the context of comorbid conditions.

Adolescent↗

PubMed2003

A latent variable model approach for assembling and scoring screening tests for dementia.

In dementia studies, the diagnosis of dementia often relies on results of screening tests aimed at measuring various dimensions of cognitive functions. The current practice of scoring a screening test involves simply summing the correct responses from each item. However, this method may be imprecise and inefficient in the predictive power of the score for dementia. We propose a latent variable model approach for the scoring and item selection of such tests. We model the item responses to be random variables based on latent variables. We also model the disease outcomes to be a function of the latent variables. Maximum likelihood estimates are obtained by maximizing the joint likelihood functions of disease and the item responses over a specified distribution function for the latent variables. Variances of model parameters are estimated using a nonparametric bootstrap method. We illustrate the approach using a screening test for dementia from a community-based study.

Aged↗

PubMed2003

Subtraction helical CT angiography of intra- and extracranial vessels: technical considerations and preliminary experience.

BACKGROUND AND PURPOSE: Reported CT angiographic (CTA) subtraction methods are not simple, robust, or real time. We investigated a novel technique for semiautomated digital subtraction CTA of the intracranial and extracranial arteries. METHODS: Thirty patients underwent precontrast (low milliampere-seconds) and postcontrast (pitch, 1.5; collimation, 1-2.5 mm) helical imaging with a vacuum-type head holder to facilitate image registration and minimize movement. A reconstructed three-dimensional model of the precontrast bone dataset was subtracted from the postcontrast dataset to produce subtracted maximum-intensity-projection angiograms. Experienced (operator 1) and less-experienced (operator 2) staff performed the standard and subtraction reconstructions, and image generation time and quality (graded 1-5) were compared. A third operator blinded to the method assessed the hard-copy image quality. RESULTS: Image quality with subtraction postprocessing was significantly better with both operators (operator 1, mean improvement of 0.87 grade, median improvement of 1 grade, P <.001; operator 2, mean improvement of 0.63 grade, median improvement of 1 grade, P <.001). Hard-copy image quality was better with the subtraction method (operator 1, P >.001; operator 2, P <.001). Blood vessels at the base of the brain were better demonstrated on subtraction images in 13 of 14 examinations. For the less experienced operator, the reconstruction time was significantly less with the subtraction method than with the conventional method (mean, 7.5 vs 10.1 minutes; P =.001). CONCLUSION: When separation of the vasculature from bone is important and technically difficult, digital subtraction CTA offers a potential advantage. This semiautomated technique is fast and easy to learn, and variably experienced staff can use it.

Adult↗