Laboratory of Functional Neuroscience, Pablo de Olavide University, Ctra. de Utrera Km 1, 41013, Seville, Spain.
CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, Madrid, Spain.
Alzheimers Res Ther. 2022 Dec 31;14(1):202. 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.
阿尔茨海默病（AD）的不可改变风险因素对皮质完整性有终生影响，如果在早期发现，这些影响可能会减轻。然而，目前尚不清楚在具有不可改变 AD 风险因素的老年个体中，皮质微观结构是否受到影响，以及在该 AD 风险人群中，改变的皮质组织完整性是否会导致大脑功能网络异常。
我们使用相对 T1w/T2w（rT1w/T2w）比值图，比较了对照组和认知正常的老年个体之间正常表现的皮质 GM 的组织完整性，这些老年个体具有 APOE4（N=50）、AD 的一级家族史（FH）（N=52）或同时具有两种 AD 风险因素（APOE4+FH）（N=35）。此外，将具有单一风险因素（APOE4 或 FH）的个体合并为一组（N=102），并与对照组进行比较。对于这些比较中的每一个，都使用年龄、性别和受教育年限相匹配的相同数量的对照组。还研究了静息状态功能连接（rs-FC）模式的组间差异，使用那些皮质区域的 rT1w/T2w 比值有显著变化的 rs-FC 种子。
总体而言，与对照组相比，具有不可改变的 AD 风险因素的个体的 rT1w/T2w 比值存在显著差异，APOE4 和 APOE4+FH 处于一个连续体的两端。APOE4 和 FH 的同时发生进一步伴随着 rs-FC 模式的改变。
这些发现可能对具有 APOE4 和/或 AD FH 的老年人群中皮质异常的早期检测具有实际意义，并为监测与不可改变的 AD 风险因素相关的皮质组织完整性变化开辟了新的途径。
