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医用画像を用いた骨粗鬆症とアルツハイマー病の連関―骨量減少に相関する脳領域の視覚化

髙野 由美 東北大学

2021.03.03

概要

骨密度低下とアルツハイマー病(Alzheimer’s Disease; AD)との関連は報告されているが、その脳内基盤は明らかではなく、医用画像を用いて詳細に検証した報告は少ない。本研究では、骨密度の低下と、AD で影響を受ける脳領域との関連を、脳容積と脳血流の変化から評価した。

骨密度と脳容積との関連(研究①)1)については、AD で障害を受けやすい領域(海馬、海馬傍回、側頭頭頂連合野、後部帯状回、楔前部)の脳皮質容積と骨密度との関連を形態画像解析 Voxel-Based Morphometry(VBM)で評価し、骨密度の低下と ADとの関連を明らかにすることを目的とした。もの忘れを主訴に受診した高齢者で、脳 Magnetic Resonance Imaging(MRI)と、骨塩定量検査である DXA(Dual-energy X- ray absorptiometry; 二重 X 線吸収)法の両検査を行った男女 149 人を対象とした。大腿骨頚部の骨密度と、VBM で取得した脳の局所灰白質容積(regional gray matter volume; rGMV)について、脳画像解析ソフトウエア Statistical parametric mapping(SPM)12 を用いてボクセルベースで相関解析を行った。年齢、性別、全脳容積と、神経心理学的検査である Mini Mental State Examination(MMSE)の結果で補正した重回帰分析で、骨密度低下と、AD で障害を受けやすい重要な神経ネットワークのハブである左楔前部の rGMV 低下に有意な相関がみられた。いわゆる “bone-brain crosstalk” を通じて、骨と脳が連関していることが示唆された。

骨密度と脳血流との関連(研究②)2)については、骨量減少(osteopenia)と診断された 65 歳以上の女性に対象を絞り、脳血流 Single-photon emission computed tomography(SPECT)と DXA の検査を行った 31 人を被験者とした。AD(n = 19)と非認知症(Non- Dementia; ND)(n = 12)に分けて、osteopenia と、局所脳領域の血流量(regional cerebral blood flow; rCBF)との関連について検討した。Osteopenia(-2.5 < T-score < -1.0)と、SPECT の定位定量的解析法である stereotactic extraction estimation analysis(SEE 解析)による脳皮質 62 領域の平均 Z-score との関連を分析した。その結果、AD で影響を受ける領域を中心とした 14 の局所脳領域で、AD 群では ND 群と比べて有意な rCBF の低下を認めた(P < 0.001)。年齢で補正した重回帰分析では、左後部帯状回の rCBF 低下が、osteopenia の独立した予測因子であった(r = -0.395; P = 0.005)。骨密度と左後部帯状回の rCBF の関係は、全対象者(r = -0.54 ; P = 0.001)、AD 群(r = -0.514; P = 0.02)で顕著な相関がみられた。これらの結果から、osteopenia が、AD に関わる脳内ネットワークの神経変性に何らかの関与をしている可能性が示唆された。

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