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White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer’s disease (AD) risk.
Method:
The present study sought to examine whether regional WMH volume mediates the relationship between APOE ε4 status, a strong genetic risk factor for AD, and cognition and if this association is moderated by age group differences within a sample of 187 healthy older adults (APOE ε4 status [carrier/non-carrier] = 56/131).
Results:
After we controlled for sex, education, and vascular risk factors, ANCOVA analyses revealed significant age group by APOE ε4 status interactions for right parietal and left temporal WMH volumes. Within the young-old group (50-69 years), ε4 carriers had greater right parietal and left temporal WMH volumes than non-carriers. However, in the old-old group (70-89 years), right parietal and left temporal WMH volumes were comparable across APOE ε4 groups. Further, within ε4 non-carriers, old-old adults had greater right parietal and left temporal WMH volumes than young-old adults, but there were no significant differences across age groups in ε4 carriers. Follow-up moderated mediation analyses revealed that, in the young-old, but not the old-old group, there were significant indirect effects of ε4 status on memory and executive functions through left temporal WMH volume.
Conclusions:
These findings suggest that, among healthy young-old adults, increased left temporal WMH volume, in the context of the ε4 allele, may represent an early marker of cognitive aging with the potential to lead to greater risk for AD.
Identifying an objective, laboratory-based diagnostic tool (e.g. changes in gene expression), when used in conjunction with disease-specific clinical assessment, could increase the accuracy of the effectiveness of a therapeutic intervention.
Methods:
We assessed the association between treatment outcome and blood RNA expression before the therapeutic intervention to post-treatment (after 1 year) of five autism spectrum disorder (ASD) toddlers who underwent an intensive cognitive-behavioural intervention integrated with psychomotor and speech therapy.
Results:
We found 113 significant differentially expressed genes enriched for the nervous system, immune system, and transcription and translation-related pathways. Some of these genes, as MALAT-1, TSPO, and CFL1, appear to be promising candidates.
Conclusions:
Our findings show that changes in peripheral gene expression could be used in conjunction with clinical scales to monitor a rehabilitation intervention’s effectiveness in toddlers affected by ASD. These results need to be validated in a larger cohort.
Recent research has revealed that cognitively unimpaired older adults who are at higher risk for developing Alzheimer’s disease (AD) dementia often exhibit subtle cognitive alterations in their neuropsychological profiles. Emerging evidence suggests that autobiographical memory, which is memory for personal events and knowledge, may be sensitive to early AD-related cognitive alterations. In the present study, we investigated whether the rapid generation of autobiographical memory category exemplars, a retrieval process that taxes the neural network that is vulnerable to early AD, is compromised in cognitively unimpaired middle-aged and older carriers of the e4 allele of the apolipoprotein E gene (APOE4), which increases risk for AD dementia.
Methods:
In addition to standard neuropsychological tests, we administered a fluency task that requires generating exemplars for two types of autobiographical memory, namely episodic memories and personal semantics, to a group of cognitively unimpaired middle-aged and older adults (n = 45) enriched with APOE4 carriers (n = 20).
Results:
While no APOE4 deficits were found on standard neuropsychological tests, episodic and personal semantic exemplar generation was reduced in the APOE4 group.
Discussion:
Autobiographical memory aberrations associated with a higher risk for AD are evident in fluency and affect both episodic memory and personal semantics.
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