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P3‐231: Separating the Concurrent Effects of Ageing and Alzheimer's Disease in the Dysregulation of Default‐Mode Network Connectivity
Author(s) -
De Marco Matteo,
Venneri Annalena
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1893
Subject(s) - default mode network , pathological , dementia , ageing , posterior cingulate , psychology , precuneus , cohort , disease , medicine , neuroscience , cortex (anatomy) , functional connectivity , cognition
Background: The Default-Mode Network (DMN) is dysregulated both by Alzheimer’s disease (AD) and, in a much milder form, over the course of non-pathological ageing. It is unclear, however, whether: 1) modifications seen in AD are simply due to the pathological intensification of the effects triggered by ageing; 2) the consequences of non-pathological ageing are actually the result of sub-clinical AD pathology (known to affect a proportion of healthy elderly individuals); 3) ageing and AD contribute to dysregulation of the DMN independently. Using linear-regression procedures this experimental question was tested in a large cohort. Methods: Twohundred-and-thirty-two individuals (including young adults, healthy seniors, and patients diagnosed with prodromal to mild AD dementia, as determined by previous neurological procedures) completed an MRI protocol including structural and functional acquisitions. The anterior and posterior DMN were estimated via group-level Independent Component Analysis carried out on the entire sample. Left hippocampal volumes were operationalised as proxies of AD burden. Days of life served as proxies of age. Multiple-regression models were run to clarify the association between AD/age and DMN connectivity, controlling for the other variable. Additional covariates were: gender, education levels, parenchymal volumes, and grey-matter fraction. Positive and negative associations were inferred, and findings were thresholded with a clusterlevel pFWE < 0.05. Results:Within the aDMN, connectivity was positively associated with age in the superior portion of the anterior-middle cingulate gyri and in prefrontal areas, and it was negatively associated with AD in the inferior portion of the anterior cingulate and the left middle frontal gyrus. Within the pDMN, connectivity was negatively associated with age in postero-medial and right temporo-insular regions, and positively associated with AD in the cuneus. Conclusions: These findings indicate that the processes of ageing and AD dysregulate different aspects of DMN connectivity, independently. Ageing seems to account for the “classic” pattern of pDMN down-regulation in the posterior-cingulate/precuneus complex, and the effects of AD net of age appear to affect instead the occipital lobe, which is normally not described as profoundly affected by neurodegeneration. These studies suggest that the effects of neurodegeneration might be in part masked by the underlying processes of ageing.