Aims: We aimed to investigate the interaction between β-amyloid (Aβ) accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes in the Alzheimer's disease (AD) clinical continuum. Background: Utility of positron emission tomography (PET) / magnetic resonance imaging (MRI) hybrid imaging for diagnostic categorization of the AD clinical continuum including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease dementia (ADD) has not been fully crystallized. Objective: To evaluate the interaction between Aβ accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes such as cortex thickness or cerebral white matter disease burden and to detect the discriminative yields of these imaging modalities in the AD clinical continuum. Methods: Fifty patients (20 women and 30 men; median age: 64 years) with clinical SCD (n=11), aMCI (n=17) and ADD (n=22) underwent PET/MRI with [18F]-fluoro-D-glucose (FDG) and [18F]- Flutemetamol in addition to cerebral blood flow (CBF) and quantitative structural imaging along with detailed cognitive assessment. Results: High Aβ deposition (increased temporal [18F]-Flutemetamol standardized uptake value ratio (SUVr) and centiloid score), low glucose metabolism (decreased temporal lobe and posterior cingulate [18F]-FDG SUVr), low parietal CBF and right hemispheric cortical thickness were independent predictors of low cognitive test performance. Conclusion: Integrated use of structural, metabolic, molecular (Aβ) and perfusion (CBF) parameters contribute to the discrimination of SCD, aMCI, and ADD.

Background: Telomeres are specific nucleotide repeats that play an important role in preventing DNA damage during cell division. Telomere length holds promise as a predictor for age‐related diseases. However, the relationship between leukocyte telomere length and structural changes in the brain is not well understood. The aim of this study is to evaluate the cross‐sectional and longitudinal relationship between telomere length, structural features of the brain, and to examine the interindividual differences in age‐related brain atrophy within the framework of biological age.Methods: A total of 202 individuals ≥50 years of age without any neurological complaints were included in the study. Telomere length measurements from the peripheral blood leukocytes and brain magnetic resonance imaging (MRI) were performed in all participants. Forty‐six of the individuals without any major health events during the follow‐up period were evaluated with a second structural brain MRI after an average of 4.7 years. The relationship between global gray matter volume change and telomere length was investigated with multivariate models. In addition, longitudinal surface‐based analysis was used to determine the relationship between telomere length and cortical thinning regionally.Results: The mean (standard deviation) age of the population was 65.9 (8.6) years; female gender constituted 60.9% of the cohort. The mean telomere length was 7.5 (2.0) kB. Telomere length was not significantly associated with brain volumes and cortical thickness. However, in the longitudinal phase of the study, we found a negative correlation between basal telomere length and the rate of total gray matter volume decrease over time (r = ‐0.370; p = 0.012). This significant relationship persisted after adjusting for age, gender, follow‐up time, and baseline total gray matter volume (Standardized β = ‐0.286, p = 0.05). Longitudinal surface‐based image analysis also revealed a negative association between telomere length and left superior parietal cortex thickness, which remained significant after cluster correction.Conclusion: Telomere length might be a predictor of age‐dependent structural changes in the brain. The left superior parietal cortex, in particular, tended to possess a vulnerability in this interplay.

Background: Telomere length (TL) has emerged as a candidate predictor for biological aging and age‐associated conditions, yet its relationship with structural brain changes remains incompletely characterized. This study aimed to investigate the cross‐sectional and longitudinal associations between TL, brain gray matter volume (GMV), white matter volume, and cortical thickness (CT) and to examine individual variability in age‐related brain changes. Methods: The study included 196 cognitively healthy individuals aged ≥50 years. All participants underwent baseline MRI and TL measurement from leukocytes. Among them, 46 individuals had a second MRI scan after an average of 4.7 years. Associations between TL and brain structural measures were assessed using multivariate models adjusting for demographic and imaging confounders. Longitudinal volumetric changes were modeled using region‐of‐interest analyses, whereas regional CT changes were examined using surface‐based methods in FreeSurfer. Results: The mean age of the cohort was 65.9 ± 8.6 years; 60.9% were women. Median TL was 7.0 kB (interquartile range [IQR]: 6.0–8.4). No significant associations were found between TL and global brain measures in the cross‐sectional analysis. However, longitudinal analysis revealed a significant inverse correlation between TL and GMV decline over time ( r = −0.370, p = 0.012), which remained robust after adjusting for age, sex, follow‐up duration, and baseline GMV (standardized β = −0.32). No significant association was found between TL and overall cortical thinning; however, at the regional level, shorter TL was significantly associated with cortical thinning in the left superior parietal lobule. Conclusion: TL may serve as a predictor of age‐dependent structural brain changes, with the left superior parietal cortex appearing particularly susceptible within this telomere‐brain aging interaction.