研究主題：探討失智症成因間的關係與影響
撰寫：學生曾子洋
血液提供大腦活動所需的氧氣與其他重要物質，腦血流量（Cerebral blood flow, CBF）作為臨床重要指標在人類維持腦部功能方面扮演關鍵角色。腦血流量的異常則可能會與中風、失智症（Dementia）等神經系統疾病有關，其中慢性的腦血流量減少可能會在核磁造影中觀察到白質高訊號（White matter hyperintensity, WMH），並導致腦白質疏鬆（Leukoaraiosis），進而造成失智症的發生。失智症不是單一項的疾病，而是不同症狀的合稱，包含記憶力的減退與認知功能的影響，其中語言能力、空間感、計算力、判斷力、抽象思考能力與注意力等方面的功能皆有可能退化。同時可能出現干擾行為、個性改變、妄想或幻覺的症狀。嚴重失智症可能影響病患的人際關係與工作能力。
失智症的主因包含最為常見的阿茲海默症（Alzheimer’s disease, AD）外，第二常見的則是血管性失智症（Vascular dementia），而皮質下缺血性腦血管疾病（Subcortical ischemic vascular disease, SIVD）則屬于血管性失智症的一個亞型。其與阿茲海默症皆有一個常見的特徵即是在皮質區域中出現腦白質疏鬆的病變，但兩者間是否存在差異仍屬未知。綜合以上，吳教授與其研究團隊即想驗證腦血流量與白質疏鬆間的關聯是否會隨著失智症的階段與主因（如阿茲海默症或皮質下缺血性腦血管疾病）而有所不同，並判斷兩者是否會對認知能力有不同的影響。
他們收集42位皮質下缺血性腦血管疾病患者、50位阿茲海默症患者與30位正常受試者，根據臨床失智評估量表將患者分為早期與晚期兩組，透過核磁造影取得腦血流量與白質高訊號之指標，並與認知能力進行相關分析。吳教授透過分層線性迴歸分析發現，腦血流量對於全局認知、記憶與注意力有顯著貢獻，相反的白質高訊號則會影響執行功能。此外吳教授發現阿茲海默症與皮質下缺血性腦血管疾病中腦血流量與白質高訊號的模式並不相同，同時也觀察到腦血流量與白質高訊號存在著空間、階段性的耦合關係；在早期的患者中，皮質區域的白質高訊號會與皮質下的腦血流量相關，但在晚期的患者中則會觀察到皮質下的白質高訊號會與皮質的腦血流量有關。透過此研究，我們可以知道腦血流量與白質高訊號具有空間耦合的關係並且會隨著失智症的進程而產生階段性的變化，而此結果也可以用做失智症患者病情進程與亞型的預測指標 [1]。
吳教授除上述的阿茲海默症相關研究外，亦有進行其他腦部、神經疾病的研究，如帕金森氏症（Parkinson’s disease）等 [2]。同時吳教授也致力核磁造影的相關技術開發、生醫信號與影像處理以及跨模組的功能比較。
Research Topic: Exploring the relationship and impact among the causes of dementia
Cerebral blood flow (CBF) plays a critical role in maintaining brain function. Abnormal CBF may associate with neurodegenerative diseases such as stroke and dementia. Chronic reduction in CBF can be observed through white matter hyperintensity (WMH) on magnetic resonance imaging, leading to the development of leukoaraiosis and subsequent occurrence of dementia. Dementia is a multifactorial disease and presents various symptoms, including memory decline and impairment of cognitive function. Language ability, spatial awareness, calculation skills, judgment, abstract thinking ability, and attention may all potentially deteriorate. Symptoms such as disruptive behavior, personality changes, delusions, or hallucinations may also occur. Severe dementia can impact interpersonal relationships and work ability of affected individuals.
The main causes of dementia include the most common Alzheimer’s disease (AD) and the second most common vascular dementia, where subcortical ischemic vascular disease (SIVD) belongs to a subtype of vascular dementia. AD and SIVD share a common characteristic of leukoaraiosis in the cortical region, but it is still unknown whether there are differences between them or not. Accordingly, Prof. Wu and his research team aim to verify whether the relationship between cerebral blood flow and leukoaraiosis varies with the stage and primary cause of dementia (such as AD and SIVD) and determine if they have different effects on cognitive abilities.
They collected data from 42 SIVD patients, 50 AD patients and 30 normal subjects. The patients were categorized into early-stage and late-stage groups based on clinical dementia rating. CBF and WMH metrics were obtained through magnetic resonance imaging and correlation analysis was conducted with cognitive abilities. Professor Wu performed hierarchical linear regression analysis and found that CBF metrics significantly contributed to global cognition, memory and attention, while WMH metrics had an impact on executive function. Furthermore, Professor Wu observed that the patterns of CBF and WMH differed between AD and SIVD, and there was a spatial and stage-dependent coupling between CBF and WMH. In early-stage patients, WMH in critical regions correlated with subcortical CBF, while in late-stage patients, WMH in subcortical regions correlated with cortical CBF. Through this study, it was determined that there is a spatial coupling between CBF and WMH and it undergoes stage-specific changes in the progression of dementia. These findings can serve as predictive indicators for the disease progression and subtypes in dementia patients [1].
In addition to the aforementioned research on Alzheimer’s disease, Professor Wu has also conducted studies on other brain and neurological disorders, such as Parkinson’s disease [2]. Furthermore, Professor Wu is dedicated to the development of related techniques in magnetic resonance imaging, biomedical signal and image processing, and cross-modal functional comparisons.
[1] Tu, M. C., Chung, H. W., Hsu, Y. H., Yang, J. J., & Wu, W. C. (2022). Stage-Dependent Cerebral Blood Flow and Leukoaraiosis Couplings in Subcortical Ischemic Vascular Disease and Alzheimer’s Disease. Journal of Alzheimer’s Disease, 86(2), 729-739. [2] Chen, C. L., Kuo, M. C., Wu, W. C., Hsu, Y. C., Wu, R. M., & Tseng, W. Y. I. (2022). Advanced brain aging in multiple system atrophy compared to Parkinson’s disease. NeuroImage: Clinical, 34, 102997.
