利用擴散磁振造影探討英國生物銀行7167名中老年人大腦白質微結構之變化

Abstract

神經纖維在正常老化和神經退化性疾病中逐漸退化。過去在神經解剖學和神經影像學研究發現，不同區域的神經纖維隨著年歲增長而退化的現象具異質性；然而，仍缺乏從中年到老年完整大腦白質隨著年齡增加退化模式的完整描述。在此，我們使用英國生物銀行的擴散磁振造影資料，來分析7167名47到76歲、神經系統正常的受試者老化過程神經纖維束的變化。擴散磁振影像和結構磁振影像資料皆在兩年內於同一台3T磁振造影掃描儀上取得，透過四個擴散指標來看神經纖維束變化率，包含概化部分不等向性(GFA )、軸向擴散係數(AD)、徑向擴散係數(RD)、平均擴散係數(MD)，編碼76條神經纖維束的神經特異變化率，可呈現出神經退化的空間形態。另外我們分析T2-FLAIR影像與年齡相關的腦白質病變(WMHL)的變化。為了探討是否有性別差異，我們依生理性別把受試者分為男性(3368名)與女性(3799名)兩族群。我們的研究發現，所有受試者的神經纖維束完整性，隨年齡增長呈現緩慢穩定的下降趨勢。在大部分的慢性退行性病變的神經纖維束中(76條中的41條)，隨著年齡增長，GFA呈下降趨勢，AD、RD和MD呈上升趨勢。這些纖維束包含大多數聯絡神經纖維(association fibers)、以及連接前額葉的投射神經纖維(projection fibers)和聯合神經纖維(commissure fibers)。另外有16條神經纖維，擴散指數隨年齡增長呈非典型變化，這些神經纖維束涉及負責快速視覺處理、學習和記憶等功能，顯示出對老化影響相對強的韌性。相較之下，WMHL累積率最高的空間形態包括圍繞側腦室的神經纖維束，佔據周腦室和深部白質區。女性受試者的纖維完整性(GFA)退化程度較男性受試者嚴重，但在WMHL並沒有顯著的性別差異。這種差異表明，這兩種截然不同的年齡相關變化之間的相互作用很弱。綜合以上所述，對老化模式的完整描述可揭示衰老或抗衰老的研究，有助於找出神經退化性疾病影像的生物標記。

Nerve fibers degenerate during normal aging and in neurodegenerative disease. Previous neuroanatomical and neuroimaging studies have found heterogeneous vulnerabilities of nerve fibers to age-related degeneration. However, a complete description of spatial and temporal patterns of degeneration over the whole brain tracts from middle to late adulthood is lacking. Here, we analyzed diffusion MRI data in the UK Biobank and estimated tract-specific age-related changes of fiber degeneration on 7167 neurologically normal participants aged 47 to 76 years. Diffusion MRI and structure MRI were acquired on the same 3T scanner within two years. Nerve fiber degeneration was estimated in terms of the rate of change in four diffusion indices, i.e. generalized fractional anisotropy (GFA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD). Spatial patterns of fiber degeneration were rendered by encoding tract-specific rates of change to 76 fiber tracts. Age-related change of white matter hyperintensity lesions (WMHL) was also analyzed on T2-FLAIR tract wise. To appreciate sex difference, male (N = 3368) and female (N = 3799) participants were displayed separately. The results showed that the study population presented a slow and monotonic decline of fiber integrity with age. The diffusion profile of chronic degeneration change, as presented with decreased GFA, increased AD, RD and MD with age, constituted the majority of the tracts (41 out of 76 tracts). The tracts included most of the association fibers, as well as the projection and commissure fibers connecting the prefrontal lobe. Another 16 tracts constituted a minority, exhibiting atypical changes of diffusion indices with age. These tracts involved the tracts responsible for fast visual processing, learning and memory, suggesting relative resilience to aging effects. In contrast, the spatial pattern of highest rates of WMHL accumulation comprised a cluster of tracts surrounding the lateral ventricle, occupying the periventricular and deep white matter regions. Female participants tended to have more profound degeneration of fiber integrity (GFA) than male participants, but there was no significant sex difference in WMHL. The disparity suggests weak interactions between these two distinct age-related changes. In conclusion, the complete description of degenerative patterns could shed light on the aging or anti-aging research, and facilitate the discovery of new imaging biomarkers of neurodegenerative disease.