Background: Given the complex and progressive nature of mild cognitive impairment (MCI), the ability to delineate and understand the heterogeneous cognitive trajectories is crucial for developing personalized medicine and informing trial design. The primary goals of this study were to examine whether different cognitive trajectories can be identified within subjects with MCI and, if present, to characterize each trajectory in relation to changes in all major Alzheimer's disease (AD) biomarkers over time.
Methods: Individuals with a diagnosis of MCI at the first visit and ≥ 1 follow-up cognitive assessment were selected from the Alzheimer's Disease Neuroimaging Initiative database (n = 936; age 73 ± 8; 40% female; 16 ± 3 years of education; 50% APOE4 carriers). Based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) total scores from baseline up to 5 years follow-up, a non-parametric k-means longitudinal clustering method was performed to obtain clusters of individuals with similar patterns of cognitive decline. We further conducted a series of linear mixed-effects models to study the associations of cluster membership with longitudinal changes in other cognitive measures, neurodegeneration, and in vivo AD pathologies.
Results: Four distinct cognitive trajectories emerged. Cluster 1 consisted of 255 individuals (27%) with a nearly non-existent rate of change in the ADAS-Cog-13 over 5 years of follow-up and a healthy-looking biomarker profile. Individuals in the cluster 2 (n = 336, 35%) and 3 (n = 240, 26%) groups showed relatively mild and moderate cognitive decline trajectories, respectively. Cluster 4, comprising about 11% of our study sample (n = 105), exhibited an aggressive cognitive decline trajectory and was characterized by a pronouncedly abnormal biomarker profile.
Conclusions: Individuals with MCI show substantial heterogeneity in cognitive decline. Our findings may potentially contribute to improved trial design and patient stratification.
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http://dx.doi.org/10.1186/s13195-023-01205-w | DOI Listing |
Mol Psychiatry
December 2024
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Psychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions.
View Article and Find Full Text PDFNat Ecol Evol
December 2024
IBE, Institute of Evolutionary Biology (UPF-CSIC), Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Ecological variation and anthropogenic landscape modification have had key roles in the diversification and extinction of mammals in Madagascar. Lemurs represent a radiation with more than 100 species, constituting roughly one-fifth of the primate order. Almost all species of lemurs are threatened with extinction, but little is known about their genetic diversity and demographic history.
View Article and Find Full Text PDFSoc Sci Med
December 2024
Michigan State University College of Human Medicine, Department of Family Medicine, 788 Service Road, East Lansing, MI, 48824, USA; Departments of Anesthesiology and Pediatrics at Michigan Medicine, USA. Electronic address:
This study examined the relative impact of earlier versus proximal childhood exposures to family adversities (parental health problems, family conflict, financial hardship, abuse, violence) and supportive caregiving (warm and supportive parenting behaviors) on youths' symptom trajectories across early adolescence. We used parent-reported survey data to differentiate co-occurring Pain, Psychological, and Somatic Symptom (Pain-PSS) trajectories among youth in the longitudinal Adolescent Brain Cognitive Development Study® (2016-2022). Family adversities and supportive caregiving were derived from youth and parent surveys and coded as occurring earlier (by age 9-11yrs; baseline) or proximally (occurring during study follow-up years 1-4; by age 11-15yrs).
View Article and Find Full Text PDFJ Intell
December 2024
Department of Development and Educational Psychology, Faculty of Psychology, University of Vienna, 1010 Vienna, Austria.
After almost a century of global generational IQ test score gains, the Flynn effect has, in the past decades, been observed to show stagnation and reversals in several countries. Tentative evidence from academic achievement data has suggested that these trajectory changes may be rooted in a decreasing strength of the positive manifold of intelligence due to increasing ability differentiation and specialization in the general population. Here, we provide direct evidence for generational IQ test score and positive manifold strength changes based on IQ test standardization data from 1392 Austrian residents between 2005 and 2018.
View Article and Find Full Text PDFMult Scler
December 2024
Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy.
Background: The effect of cognitive reserve (CR) on cognition in people with relapsing-remitting multiple sclerosis (pwRRMS) has been partially investigated.
Objectives: We aimed to explore the long-term cognitive trajectories of pwRRMS based on their CR, measured using the Vocabulary Knowledge Test (VOC).
Methods: 78 pwRRMS underwent a neuropsychological evaluation at baseline and after a mean follow-up of 6.
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