Effects of non-modifiable risk factors of Alzheimer's disease on intracortical myelin content

• Published in: Alzheimer's research & therapy Vol. 14; no. 1; p. 202
• Main Authors: Fernandez-Alvarez, Marina, Atienza, Mercedes, Cantero, Jose L
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.12.2022; BioMed Central; BMC
• Subjects: Aged; Aging; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer's disease; APOE4; Apolipoprotein E4 - genetics; Brain; Brain research; Care and treatment; Cortical maps; Cortical microstructure integrity; Development and progression; Family history; Genetic aspects; Health aspects; Humans; Intracortical myelin; Magnetic Resonance Imaging; Membrane proteins; Myelin Sheath; Neural circuitry; Risk Factors; Spain; Functional connectivity; T1w/T2w ratio maps; Cortical microstructure integrity; Alzheimer’s disease; APOE4; Aging; Intracortical myelin; Family history
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-022-01152-y

Non-modifiable risk factors of Alzheimer's disease (AD) have lifelong effects on cortical integrity that could be mitigated if identified at early stages. However, it remains unknown whether cortical microstructure is affected in older individuals with non-modifiable AD risk factors and whether altered cortical tissue integrity produces abnormalities in brain functional networks in this AD-risk population. Using relative T1w/T2w (rT1w/T2w) ratio maps, we have compared tissue integrity of normal-appearing cortical GM between controls and cognitively normal older adults with either APOE4 (N = 50), with a first-degree family history (FH) of AD (N = 52), or with the co-occurrence of both AD risk factors (APOE4+FH) (N = 35). Additionally, individuals with only one risk factor (APOE4 or FH) were combined into one group (N = 102) and compared with controls. The same number of controls matched in age, sex, and years of education was employed for each of these comparisons. Group differences in resting state functional connectivity (rs-FC) patterns were also investigated, using as FC seeds those cortical regions showing significant changes in rT1w/T2w ratios. Overall, individuals with non-modifiable AD risk factors exhibited significant variations in rT1w/T2w ratios compared to controls, being APOE4 and APOE4+FH at opposite ends of a continuum. The co-occurrence of APOE4 and FH was further accompanied by altered patterns of rs-FC. These findings may have practical implications for early detection of cortical abnormalities in older populations with APOE4 and/or FH of AD and open new avenues to monitor changes in cortical tissue integrity associated with non-modifiable AD risk factors.