👤 Ralph L Sacco

Accurate Alzheimer's disease (AD) detection remains challenging and often requires invasive or costly procedures. Blood-based metabolomic signatures offer a promising non-invasive approach. This study aimed to identify a serum metabolite panel and evaluate its performance alone and in combination with Baseline data from 594 participants in the Alzheimer's Disease Neuroimaging Initiative (237 AD, 357 CN) were analyzed. High-resolution serum metabolomics (Biocrates MxP® Quant 500) and A panel of 151 metabolites distinguished AD from CN with high accuracy (test-set AUC=0.90). Adding Integrating serum metabolomics with NCT00106899 and related ADNI phases. Show less

Retirement is a major life transition that can alter patterns of movement behaviors (physical activity, sedentary behavior and sleep). While some studies indicate an increase in physical activity post-retirement, others report a rise in sedentary behavior. However, evidence is lacking on how individuals re-allocate time among movement behaviors, particularly using analytical approaches that account for the co-dependence of 24-hour time-use data. Furthermore, little is known about how pre-retirement occupational physical activity (OPA) levels influence physical activity after retirement. This study examined changes in the relative time spent in sleep, sedentary behavior (SB), light physical activity (LPA), and moderate-vigorous physical activity (MVPA) over retirement, and how these changes vary by pre-retirement OPA levels. Data were drawn from the Swedish Retirement Study, which followed 112 participants (47 men, 65 women; age: 60–72) at three timepoints during the retirement transition. Movement behavior and sleep data were collected over a week-long period using thigh-worn accelerometers and wrist-worn actigraphs. Compositional data analysis (CoDA) was employed to account for the co-dependent nature of 24-hour time-use data. Multivariable linear mixed models, adjusted for sociodemographic and health covariates, were used to evaluate the associations between retirement, OPA tertiles, and movement behaviors. In the overall sample, changes in movement behaviors mainly involved sleep. However, substantial variation was observed across OPA tertile groups. The sleep-to-wake time ratio increased in the high OPA group and, to a lesser extent, in the medium OPA group. Regarding physically active and sedentary time, a convergence between the high and low OPA groups was observed, as pre-retirement differences diminished. Specifically, the ratio of physically active time to SB decreased in the high OPA group and increased in the low OPA group. The findings indicate that pre-retirement OPA is a significant factor in understanding changes in movement behaviors during the retirement transition. The reduction in post-retirement physical activity among high-OPA workers may represent a healthier rebalancing rather than a decline, which aligns with the “physical activity paradox” and the “Sweet-Spot Hypothesis”. This evidence highlights the need for tailored interventions for retirees, particularly those from physically demanding occupations. The online version contains supplementary material available at 10.1186/s11556-025-00395-6. Show less

Carotid plaque is a marker of subclinical atherosclerosis with a genetic component. The aim of this follow-up fine mapping study was to identify candidate genes for carotid plaque within four linkage regions. We successfully genotyped 3712 single nucleotide polymorphisms (SNPs) under the four linkage regions that were previously identified in 100 extended Dominican families. Family-based association tests were performed to investigate their associations with carotid plaque. Promising SNPs were evaluated in an independent population-based subcohort (N=941, 384 Dominicans) from the Northern Manhattan Study (NOMAS). In the family study, evidence for association (p<0.0005) was found regarding several genes (NAV2, EFCAB11/TDP1, AGBL1, PTPN9, LINGO1 and LOC730118), with the strongest association at rs4143999 near EFCAB11/TDP1 (p=0.00001 for carotid presence and 0.00003 for plaque area, multiple testing corrected p≤0.02). The association in AGBL1 and PTPN9 was mainly driven by the families with linkage evidence (p=0.00008-0.00001 and 0.76-0.32, respectively, in the families with and without linkage evidence). However, these associations explained only a small portion of the observed linkage. In NOMAS, replication (p<0.05 in the whole NOMAS subcohort and p<0.10 in the smaller Dominican subcohort) was found for SNPs within/near EFCAB11, NAV2, AGBL1 and other genes. This follow-up study has identified multiple candidate genes for carotid plaque in the Dominican population. Many of these genes have been implicated in neurodegenerative and cardiovascular diseases. Further studies with in-depth re-sequencing are needed to uncover both rare and common functional variants that contribute to the susceptibility to atherosclerosis. Show less