海馬迴相關腦結構與主觀認知下降患者記憶力訓練改善之關係

Abstract

隨著平均預期壽命的增加，失智症的發病率也逐漸升高。越來越多的研究指出，神經影像對於診斷阿茲海默症（Alzheimer’s disease, AD）前驅階段扮演重要角色。而認知訓練已被證實有助於老年人提高認知能力。然而，阿茲海默症前驅階段的神經影像學與認知訓練之間的關係尚未得到充分研究。因此，我們蒐集了主觀認知能力下降患者（subjective cognitive decline, SCD）和輕度認知功能障礙患者（mild cognitive impairment, MCI）的擴散頻譜影像，並探討與記憶功能，記憶功能改善之間的關聯性。所有受試者均於 3T 磁振造影儀上進行大腦的T1 權重結構影像(T1WI)與擴散頻譜影像(diffusion spectrum imaging, DSI)掃描。接著，我們透過全腦基於神經束之自動化分析(Tract-based automatic analysis, TBAA)獲得擴散指標，並用以反應白質結構損傷程度，包括部分非等向性指標(fractional anisotropy, FA)、軸向擴散指標（axial diffusivity, AD）、徑向擴散指標（radial diffusivity, RD）和平均擴散指標（mean diffusivity, MD）。並透過解剖計算工具（Computational Anatomy Toolbox, CAT12）且使用LONI分區模板（LONI Probabilistic Brain Atlas, LPBA40）計算大腦灰質體積（gray matter, GM）。此外，我們使用標準模型（normative model）將白質纖維束及灰質體積標準化，並與同年齡、同性別族群匹配，計算出擴散指數及灰質體積之標準分數(Z-score)。 本研究招募了兩組參與者：31名主觀認知能力下降患者與25名輕度認知功能障礙患者。研究結果顯示，主觀認知能力下降患的海馬迴相關平均擴散指標的標準分數與蒙特利爾認知評估量表(Montreal Cognitive Assessment, MoCA)及簡易心智量表（Mini-Mental State Examination, MMSE）子項目總分之間呈顯著負相關。在灰質中，與各種記憶得分無關。經過三個月的認知訓練後，在主觀認知能力下降患者中發現,較低的海馬迴相關平均z值與MMSE + MOCA子項目總分的改善相關。相比之下，海馬迴，海馬迴旁的灰質體積與各種記憶分數的改善之間沒有相關。 總結:在阿茲海默症前驅階段，記憶功能可能與白質有關,而不是灰質。此外，從研究結果可以推斷，針對失智症前驅階段較早期的認知訓練介入,對於記憶功能的改善將有較多的幫助。

The incidence of dementia appears to be rising with a higher average life expectancy. More and more research proposed that neuroimaging can provide crucial biomarkers to detect the prodromal stage of Alzheimer’s disease (AD). The cognitive training has been validated to be helpful for the elderly to improve cognition. However, the relationship between neuroimaging and cognitive training in the prodromal stage of AD has not been fully investigated yet. Therefore, the present study collected diffusion and structural MRI data from patients with subjective cognitive decline (SCD) and those with mild cognitive impairment (MCI), and investigated the correlations of MRI metrics with memory performance, and memory performance improvement. Two groups of participants, SCD (N = 31) and MCI (N = 25), were recruited. All participants underwent diffusion spectrum imaging (DSI) and T1-weighted imaging (T1WI) of the brain on a 3T MRI scanner. We used tract-based automatic analysis (TBAA) to obtain diffusion indices to indicate white matter (WH) microstructure property; the indices included fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD). We also calculated gray matter (GM) volume by using LONI probabilistic brain atlas (LPBA40) and computational anatomy toolbox (CAT12). In addition, we used a normative model to assess the age-matched, sex-matched population, and calculate the z-score of diffusion index and gray matter volume. The results showed a significant negative correlation between the hippocampal-related average diffusion z-scores and MMSE+MOCA sub-item scores in the SCD group. In gray matter, there was no relationship with any kind of memory scores. After cognitive training, the hippocampal-related average z-scores were significantly correlated with MMSE+MOCA sub-item improvement in the SCD group. In contrast, there was no correlation between the hippocampus, para-hippocampal GM, with any kind of memory improvement. In conclusion, in the prodromal stages of AD, the memory performance is associated with white matter instead of the gray matter property metrics. Our findings also imply that the earlier cognitive training for the prodromal stage of dementia, the better improvement for the memory function.