Gray Matter Densities in Limbic Areas and APOE4 Independently Predict Cognitive Decline in Normal Brain Aging

Wyss

et al. 2019

Front. Aging Neurosci.

Objectives To assess the influence of age and sex on 10 cerebrospinal fluid (CSF) flow dynamics parameters measured with an MR phase contrast (PC) sequence within the cerebral aqueduct at the level of the intercollicular sulcus. Materials and Methods 128 healthy subjects (66 female subjects with a mean age of 52.9 years and 62 male subjects with a mean age of 51.8 years) with a normal Evans index, normal medial temporal atrophy (MTA) score, and without known disorders of the CSF circulation were included in the study. A PC MR sequence on a 3T MR scanner was used. Ten different flow parameters were analyzed using postprocessing software. Ordinal and linear regression models were calculated. Results The parameters stroke volume (sex: p < 0.001, age: p = 0.003), forward flow volume (sex: p < 0.001, age: p = 0.002), backward flow volume (sex: p < 0.001, age: p = 0.018), absolute stroke volume (sex: p < 0.001, age: p = 0.005), mean flux (sex: p < 0.001, age: p = 0.001), peak velocity (sex: p = 0.009, age: p = 0.0016), and peak pressure gradient (sex: p = 0.029, age: p = 0.028) are significantly influenced by sex and age. The parameters regurgitant fraction, stroke distance, and mean velocity are not significantly influenced by sex and age. Conclusion CSF flow dynamics parameters measured in the cerebral aqueduct are partly age and sex dependent. For establishment of reliable reference values for clinical use in future studies, the impact of sex and age should be considered and incorporated.

Section: Discussionmentioning

confidence: 99%

Sex and Age Dependencies of Aqueductal Cerebrospinal Fluid Dynamics Parameters in Healthy Subjects

Wyss

et al. 2019

Front. Aging Neurosci.

“…Cognitive trajectories were defined after summing the number of cognitive tests at follow-up with performances at least 0.5 standard deviation (SD) higher or lower compared with the first evaluation ( Z scores). Change in cognition between inclusion and last follow-up was defined as the sum of the continuous cognitive scores at two follow-ups as previously described ( 25 , 30 ).…”

Section: Methodsmentioning

confidence: 99%

“…At baseline, all individuals were evaluated with a neuropsychological battery described in detail previously (27,(29)(30)(31). All individuals were also evaluated with the Clinical Dementia Rating scale (CDR) (32).…”

Section: Neuropsychological Assessmentmentioning

confidence: 99%

Personality Factors' Impact on the Structural Integrity of Mentalizing Network in Old Age: A Combined PET-MRI Study

et al. 2020

Self Cite

The mentalizing network (MN) treats social interactions based on our understanding of other people's intentions and includes the medial prefrontal cortex (mPFC), temporoparietal junction (TPJ), posterior cingulate cortex (PCC), precuneus (PC), and amygdala. Not all elders are equally affected by the aging-related decrease of mentalizing abilities. Personality has recently emerged as a strong determinant of functional connectivity in MN areas. However, its impact on volumetric changes across the MN in brain aging is still unknown. To address this issue, we explored the determinants of volume decrease in MN components including amyloid burden, personality, and APOE genotyping in a previously established cohort of 130 healthy elders with a mean follow-up of 54 months. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models corrected for multiple comparisons were used to identify predictors of volume loss including time, age, sex, personality, amyloid load, presence of APOE epsilon 4 allele, and cognitive evolution. In cases with higher Agreeableness scores, there were lower volume losses in PCC, PC, and amygdala bilaterally. This was also the case for the right mPFC in elders displaying lower Agreeableness and Conscientiousness. In multiple regression models, the effect of Agreeableness was still observed in left PC and right amygdala and that of Conscientiousness was still observed in right mPFC volume loss (26.3% of variability, significant age and sex). Several Agreeableness (Modesty) and Conscientiousness (order, dutifulness, achievement striving, and self-discipline) facets were positively related to increased volume loss in cortical components of the MN. In conclusion, these data challenge the beneficial role of higher levels of Agreeableness and Conscientiousness in old age, showing that they are associated with an increased rate of volume loss within the MN.

“…Finally, by combining US population-based incidence rates and the genotype-derived PHS for each individual, estimates of instantaneous risk (i.e., cumulative incidence rate) for developing AD were derived based on genotype and age ( Desikan et al, 2017 ; Tan et al, 2019 ). Considering APOE is strongly associated with both cognition and hippocampal volumes even in very early cases ( Haller et al, 2019 ; Herrmann et al, 2019 ), we have completed all the analyses including APOE genotype as a covariate.…”

Section: Methodsmentioning

confidence: 99%

“…HP, hippocampus; ML, the molecular layer; CA, cornus ammonis; GC-ML-DG, the molecular and granule cell layers of the dentate gyrus; HATA, hippocampal amygdala transition area. (Haller et al, 2019;Herrmann et al, 2019), we have completed all the analyses including APOE genotype as a covariate.…”

Section: Polygenic Hazard Scorementioning

confidence: 99%

Polygenic hazard score modified the relationship between hippocampal subfield atrophy and episodic memory in older adults

Guan²,

Wen³

et al. 2022

Front. Aging Neurosci.

BackgroundUnderstanding genetic influences on Alzheimer’s disease (AD) may improve early identification. Polygenic hazard score (PHS) is associated with the age of AD onset and cognitive decline. It interacts with other risk factors, but the nature of such combined effects remains poorly understood.Materials and methodsWe examined the effect of genetic risk and hippocampal atrophy pattern on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD using structural MRI. Participants included 51 memory unimpaired normal control (NC), 69 mild cognitive impairment (MCI), and 43 AD adults enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Hierarchical linear regression analyses examined the main and interaction effects of hippocampal subfield volumes and PHS, indicating genetic risk for AD, on a validated episodic memory composite score. Diagnosis-stratified models further assessed the role of PHS.ResultsPolygenic hazard score moderated the relationship between right fimbria/hippocampus volume ratio and episodic memory, such that patients with high PHS and lower volume ratio had lower episodic memory composite scores [ΔF = 6.730, p = 0.011, ΔR2 = 0.059]. This effect was also found among individuals with MCI [ΔF = 4.519, p = 0.038, ΔR2 = 0.050]. In contrast, no interaction effects were present for those NC or AD individuals. A follow-up mediation analysis also indicated that the right fimbria/hippocampus volume ratio might mediate the link between PHS and episodic memory performance in the MCI group, whereas no mediation effects were present for those NC or AD individuals.ConclusionThese findings suggest that the interaction between AD genetic risk and hippocampal subfield volume ratio increases memory impairment among older adults. Also, the results highlighted a potential pathway in which genetic risk affects memory by degrading hippocampal subfield volume ratio in cognitive decline subjects.