論文No1634
Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study
Ram A. Sharma, Andrew W. Varga, Omonigho M. Bubu, Elizabeth Pirraglia, Korey Kam, Ankit Parekh, Margaret Wohlleber, Margo D. Miller, Andreia Andrade, Clifton Lewis, Samuel Tweardy, Maja Buj, Po L. Yau, Reem Sadda, Lisa Mosconi, Yi Li, Tracy Butler, Lidia Glodzik, Els Fieremans, James S. Babb, Kaj Blennow, Henrik Zetterberg, Shou E. Lu, Sandra G. Badia, Sergio Romero, Ivana Rosenzweig, Nadia Gosselin, Girardin Jean-Louis, David M. Rapoport, Mony J. de Leon, Indu Ayappa, Ricardo S. Osorio
AJRCCM, Vol. 197, No. 7 | Apr 01, pp. 933–943, 2018.
＜背景＞
閉塞性睡眠時無呼吸(OSA)は軽度認知機能障害、アルツハイマー秒のリスク因子である。
しかし、OSAがどのように縦断的にアルツハイマー病に影響するかはよくわかっていない。
＜目的＞
OSAの重症度と縦断的なアミロイド増加に関連があるかを認知機能が正常な成人で検討した。
＜方法＞
健康な認知機能が正常の成人に２年にわたって縦断的に前向き研究を行った。
55歳から90歳の健康ボランティアで、うつがなく、臨床的に認知機能が正常と診断された人を対象とした。
脳脊髄液のアミロイドβをELISA法で測定した。
標準的方法でピッツバーグ複合BのPETスキャンを受けた。
OSAのモニタリングは家庭睡眠記録デバイスで検査した。
＜結果＞
OSAの重症度(AHIall [F1,88 = 4.26; P < 0.05] and AHI4% [F1,87 = 4.36; P < 0.05])は、
年齢、性別、BMI、アポリポ蛋白E4で補正後に
脳脊髄液のアミロイドβ42の年次変化率と線形回帰分析で相関していた。
AHIall、AHI4%はADPiB-mask (Alzheimer’s disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask)の増加と関連しなかったが、
サンプルサイズが小さかったためかもしれない。
しかし、AHIallとは関連する傾向をみとめた(F1,28 = 2.96, P = 0.09; and F1,28 = 2.32, not significant, respectively)。
＜感想＞
認知機能が正常群において、OSAの重症度は脳脊髄液中のアミロイドβの増加と２年の追跡で関連したようです。
OSAによる睡眠分断や間欠的低酸素が原因として推測されます。
Rationale: Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer’s disease. However, how sleep apnea affects longitudinal risk for Alzheimer’s disease is less well understood.
Objectives: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly.
Methods: Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device.
Measurements and Main Results: We found that severity of OSA indices (AHIall [F1,88 = 4.26; P < 0.05] and AHI4% [F1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in ADPiB-mask (Alzheimer’s disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F1,28 = 2.96, P = 0.09; and F1,28 = 2.32, not significant, respectively).
Conclusions: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.