Both objective and perceived social isolations were associated with future cognitive decline and increase risk of Alzheimer’s disease (AD). However, the impacts of perceived social isolation depending on different clinical stages of AD have not been elucidated. The aim of this study was to investigate the influence of perceived social isolation or loneliness on brain structure and future cognitive trajectories in patients who are living with or are at risk for AD. A total of 176 elderly patients (mean age of 78 years) who had complaint of memory problems (39 subjective cognitive decline [SCD], 53 mild cognitive impairment [MCI], 84 AD) underwent structural MRI and neuropsychological testing. Loneliness was measured by one binary item question “Do you often feel lonely?.” Voxel-based morphometry was conducted to evaluate regional gray matter volume (rGMV) difference associated with loneliness in each group. To evaluate individual differences in cognitive trajectories based on loneliness, subgroup analysis was performed in 51 patients with AD (n = 23) and pre-dementia status (SCD-MCI, n = 28) using the longitudinal scores of Alzheimer’s Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog). Whole brain VBM analysis comparing lonely to non-lonely patients revealed loneliness was associated with decreased rGMV in bilateral thalamus in SCD patients and in the left middle occipital gyrus and the cerebellar vermal lobules I − V in MCI patients. Annual change of ADAS-Jcog in patients who reported loneliness was significantly greater comparing to these non-lonely in SCD-MCI group, but not in AD group. Our results indicate that perceived social isolation, or loneliness, might be a comorbid symptom of patients with SCD or MCI, which makes them more vulnerable to the neuropathology of future AD progression.

客观和感知的社会孤立都与未来的认知能力下降和阿尔茨海默病 (AD) 的风险增加有关。然而，尚未阐明依赖于 AD 不同临床阶段的感知社会隔离的影响。本研究的目的是调查感知到的社会孤立或孤独感对患有 AD 或有患 AD 风险的患者的大脑结构和未来认知轨迹的影响。共有 176 名老年患者（平均年龄 78 岁）抱怨记忆问题（39 名主观认知下降 [SCD]、53 名轻度认知障碍 [MCI]、84 名 AD）接受了结构 MRI 和神经心理学测试。孤独是通过一个二元题“你经常感到孤独吗？”来衡量的。” 进行了基于体素的形态测量，以评估每组与孤独感相关的区域灰质体积 (rGMV) 差异。为了评估基于孤独感的认知轨迹的个体差异，对 51 名 AD 患者进行了亚组分析。n  = 23）和痴呆前状态（SCD-MCI，n  = 28）使用阿尔茨海默病评估量表的纵向评分-认知成分-日语版 (ADAS-Jcog)。比较孤独患者与非孤独患者的全脑 VBM 分析显示，孤独与 SCD 患者双侧丘脑和 MCI 患者左侧枕中回和小脑蚓部 I-V 的 rGMV 降低有关。在 SCD-MCI 组中，报告孤独感的患者 ADAS-Jcog 的年度变化显着大于非孤独患者，但在 AD 组中则不然。我们的研究结果表明，感知到的社会孤立或孤独感可能是 SCD 或 MCI 患者的共病症状，这使他们更容易受到未来 AD 进展的神经病理学的影响。