- 學位論文
阿茲海默症之睡眠障礙:一中台灣橫斷性研究
Sleep disturbances in Alzheimer's disease: A cross-sectional study in central Taiwan
摘要
隨著台灣人口快速老化，阿茲海默症患者 (Alzheimer’s disease；AD)的盛行率也不斷增加。過去研究顯示AD患者常合併睡眠障礙，此將進一步惡化其已受損之生活功能與生活品質；AD患者有睡眠障礙者常會帶給照顧者相當的壓力。探討AD的睡眠問題本質，有助於改善AD患者的睡眠問題。本研究的主要目的有三：(1) 了解阿茲海默症個案睡眠障礙的盛行率及其睡眠障礙形態，並探討影響AD個案睡眠障礙的相關因素；(2) 探討影響AD個案睡眠障礙對於照顧者的情緒健康衝擊; (3) 藉多項睡眠生理腦波儀了解AD患者睡眠形態與其原發性睡眠障礙的比例。 此研究為一多中心的研究，於中山醫學大學神經內科與精神科、林新醫院神經內科、秀傳醫院神經內科與精神科等三處醫院，以門診臨床個案為研究群體之兩年期非隨機橫斷性研究，研究個案需符合DSM IV及NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association) 疑似阿茲海默症之診斷要件；個案目前居住於社區中，本人或其主要照顧者可以瞭解研究內容且願意簽署同意書。計劃於民國99年至101年間收集300名以上AD個案及其主要照顧者。評估項目為：個案之認知功能、生活自理能力、睡眠品質 (以Pittsburgh Sleep Quality Index評估)、日間嗜睡程度 (Epworth Sleepiness Scale評估)、憂鬱程度 (以Cornell Scale for Depression in Dementia評估)、精神與行為症狀 (Behavioral and psychological symptoms of dementia；BPSD以Neuropsychiatric Inventory；NPI評估)、生活壓力事件 (以List of Threatening Experiences評估)、照顧者身心健康 (以CES-D評估憂鬱傾向)與負荷程度 (以The Zarit Caregiving Burden Scale評估)。此外，部分個案接受多項睡眠生理腦波儀檢查 (polysomnography；PSG)，以了解原發性睡眠障礙之盛行率。 本研究共計有三百九十二位疑似阿茲海默症之個案參與。其中103位 (26.3%) 為早期失智，177位 (45.2%) 為輕度失智，104位 (26.5%)為中度失智，8位 (2.0%) 為重度失智。以NPI之睡眠障礙分項評估，65.6%的個案有嚴重程度不一的睡眠障礙，隨著失智程度惡化，睡眠障礙的頻率與嚴重度逐漸惡化。而以Pittsburgh Sleep Quality Index評估個案睡眠品質，發現輕度失智程度的睡眠品質相對於其他失智程度，有較佳的傾向。隨著失智程度惡化，睡眠品質有更為嚴重的傾向，睡眠品質之良窳與失智病程的關係，略呈U-型的形態。個案自評健康較佳者，有較好的睡眠品質。此外，女性、日常生活功能不佳與憂鬱程度較高的個案，其睡眠品質較差。而隨著失智程度的惡化，個案之日間嗜睡程度趨於嚴重、睡眠效率則越差。日間較嗜睡與不佳之睡眠效率影響個案之日常生活功能；此外，日間嗜睡也與個案之憂鬱、認知功能差有關。90.8%個案至少有一項精神與行為症狀，失智越嚴重，BPSD各症狀的盛行率也越高；其中65.6%有不等程度的睡眠障礙，為盛行率最高的症狀。有睡眠障礙者在各臨床特徵上 (如:認知功能、日常生活功能、憂鬱程度與NPI嚴重度等)，都較沒有睡眠障礙者差。於精神與行為症狀評估中存在有睡眠障礙的個案，較常共病其他行為與精神症狀。失智症個案照顧者的負擔 (以The Zarit Caregiving Burden Scale評估) 與阿茲海默症個案睡眠障礙造成照顧者困擾的程度有關 (r=0.267; P<.0001)；照顧者負擔與NPI嚴重度的相關係數更高達0.452 (P<.0001)。在個案睡眠障礙的型態上，半夜遊走、半夜吵醒照顧者的盛行率雖非最高，但對於照顧者的困擾卻最嚴重。多達34.2%的照顧者的憂鬱達顯著程度 (CES-D≥16)，顯見阿茲海默症個案之照顧者心理健康程度值得重視。個案之認知功能、憂鬱傾向、日間嗜睡程度與行為與精神症狀的嚴重度等，乃照顧者憂鬱之預測因子。五十一位接受PSG檢查的個案，高達90.2%呈現不同嚴重程度的睡眠呼吸中止症；31.6%的個案於睡眠檢查中呈現陣發性肢體運動疾患。 阿茲海默症個案睡眠障礙的盛行率相當高，在疾病早期便已帶給個案相當程度的困擾；隨著病程的惡化，睡眠障礙有趨於嚴重的傾向。睡眠障礙、日間嗜睡與不佳之睡眠效率影響個案之認知功能與日常生活功能。個案的睡眠障礙帶給其照顧者相當程度的負擔與負面心理健康的衝擊。個案合併睡眠呼吸中止症與陣發性肢體運動疾患的比例不低，對於個案的認知功能與睡眠品質有不良的影響。進一步前驅性的世代研究將有助於了解阿茲海默症個案睡眠障礙的演變以及對於個案功能的影響。
並列摘要
The prevalence of Alzheimer’s disease (AD) increased as the population in Taiwan aged rapidly recently. Previous studies have shown that many patients of AD suffered from sleep disturbances. For patients with AD, sleep problems exert an additional burden to the compromised functioning and quality of life. In addition, disrupted sleep in patients with AD is a significant cause of stress for caregivers and frequently leads to institutionalization of patients. For resolution of this problem, the nature of sleep disturbance of AD should be clarified. However, few studies had addressed this issue in Taiwan. The primary aims of present study encompass three parts: (1) to elucidate the prevalence and nature of sleep disturbances and its correlates in community-dwelling patients of AD. (2) to investigate the impact and burden in the caregivers of patients with AD brought by sleep disturbance. (3) to explore the prevalence of primary sleep disorder in patients with AD by the aids of polysomnography. The present study is a cross-sectional, multi-centers’ study. The study was carried out at Chung Shan Medical University Hospital, Show Chwan Memorial Hospital and Lin Shin Hospital in the period of 2010 to 2012. Eligible criteria of participants are: (1) meet the DSM IV and NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association) criteria as probable or possible AD, (2) dwell in community and live with caregivers, and (3) able to understand and provide written informed consent themselves or provide informed consent by caregivers. The assessment items include cognitive function, self-care function, sleep quality (Pittsburgh Sleep Quality Index), daytime drowsiness (Epworth Sleepiness Scale), threatening life events as well as behavioral and psychological symptoms of dementia (Neuropsychiatric Inventory ; NPI). Mental health and burden of caregivers are also inquired. Fifty-one patients received one-night polysomnographic examination (PSG). A total of 392 participants were recruited. Among them, 103 persons (26.3%) were in early stage of dementia; 177 persons (45.2%) were categorized as mild dementia, 104 persons (26.5%) as moderate dementia and 8 persons as severe dementia. Two hundred and fifty seven participants (65.6%) suffered from a variety degree of sleep disturbances by NPI assessment, the frequency and severity of sleep disturbances in patients of AD increased as the severity of dementia progressed. Using Pittsburgh Sleep Quality Index to assess sleep quality of AD patients, the prevalence and severity of sleep disturbances were relatively low in mild dementia. As dementia progressed, the impact of sleep disturbances got worse. Patients themselves rated better self-health enjoyed better sleep quality. The determining factors of worse sleep quality included women, poor self-care functioning and greater depressive tendency. Poor sleep efficiency and severe daytime drowsiness were correlated with worsening dementia degree. Increased daytime drowsiness was associated with more depressive tendency and worse cognitive functioning. Nearly ninety percent of patients exhibited at least one item of behavioral and psychological symptoms. There was high comorbidity between sleep disturbance and other behavioral and psychological symptoms in NPI evaluation. Patients with sleep disturbance by NPI assessment demonstrated poorer cognitive functioning, worse daily functioning and more depressive tendency. The burden of caregivers was significantly associated with the caregivers’ distress from sleep disturbances in AD (r=0.267; P<.0001). Besides, caregivers’ burden was highly associated with NPI score (0.452; P<.0001). In the pattern of sleep disturbance, although nighttime wandering and awakening caregivers were not the most prevalent items, they were rated as most distressing experiences by caregivers. Thirty-four percent of caregivers suffered from significant depression in Center for Epidemiologic Studies Depression Scale (CES-D) evaluation. Further effort should be exerted to enhance mental health of caregivers in AD. Of 51 patients receiving PSG examination, the prevalence of sleep apnea was very high (90.2%); followed by periodic limb movement (31.6%). The prevalence of sleep disturbances in AD patients is very high even in the early stage of illness. As AD illness course progressed, the impact of sleep disturbances got worse. A substantial numbers of AD patients also suffered from primary sleep disorders, mostly sleep apnea and periodic movement disorder. The burden to caregivers brought from sleep disturbance was huge in AD. Further cohort study is needed to elucidate the progression of sleep disturbances in AD as well as its impact on functioning of AD patients.