Smaller pineal gland is associated with rapid eye movement sleep behavior disorder in Alzheimer’s disease

Abstract

Background To investigate the association between pineal gland volume and symptoms of rapid eye movement (REM) sleep behavior disorder (RBD) in Alzheimer’s disease (AD) patients without any feature of dementia with Lewy bodies. Methods We enrolled 296 community-dwelling probable AD patients who did not meet the diagnostic criteria for possible or probable dementia with Lewy bodies. Among them, 93 were amyloid beta (Aβ) positive on 18F-florbetaben amyloid brain positron emission tomography. We measured RBD symptoms using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and defined probable RBD (pRBD) as the RBDSQ of 5 or higher. We manually segmented pineal gland on 3T structural T1-weighted brain magnetic resonance imaging. Results The participants with pRBD had smaller pineal parenchyma volume (VPP) than those without pRBD (p < 0.001). The smaller the VPP, the more severe the RBD symptoms (p < 0.001). VPP was inversely associated with risk of prevalent pRBD (odds ratio = 0.909, 95% confidence interval [CI] = 0.878–0.942, p < 0.001). Area under the receiver operator characteristic curve for pRBD of VPP was 0.80 (95% CI = 0.750–0.844, p < 0.0001). These results were not changed when we analyzed the 93 participants with Aβ-positive AD separately. Conclusions In AD patients, reduced pineal gland volume may be associated with RBD.

Brain Functional and Structural Changes in Alzheimer's Disease With Sleep Disorders: A Systematic Review

“…In these studies, one single-photon emission computed tomography (SPECT) ( 22 ) study and one multislice spiral computed tomography perfusion imaging (MSCTP) ( 26 ) study investigated changes of cerebral blood flow; two whole-brain structural magnetic resonance imaging (sMRI) studies investigated brain structural changes ( 27 , 28 ), one sMRI study investigated the brain stem volume ( 24 ), and another investigated the pineal gland volume ( 30 ); two resting-state functional magnetic resonance imaging (rs-fMRI) studies investigated brain functional changes ( 23 , 29 ); and one 2-deoxy-2-(18F) fluoro-d-glucose positron emission tomography (18F-FDG-PET) investigated 18F-FDG-PET uptake in patients with comorbid AD and SLD ( 25 ).…”

“…Diagnosis and evaluation of AD and SLD are heterogeneous. In AD diagnosis, four studies used National Institute of Neurological and Communicative Disorders and stroke—AD and related disorders association criteria (NINCD) ( 22 – 24 , 28 ), one used National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for AD (NIAAA) ( 25 ), one used a consortium to establish a registry for AD assessment packet clinical assessment battery (CERAD) ( 30 ), one used Chinese Classification of Mental Disorders version 3 (CCMD-3) ( 26 ), one used National Institute of Aging-Alzheimer's criteria in 2011 (NIAA) ( 29 ), and one did not provide a diagnostic standard ( 27 ). In SLD evaluation, three used a sleep subscale of neuropsychiatric inventory (sNPI) ( 22 , 24 , 28 ), three used the Pittsburgh sleep quality index (PSQI) ( 26 , 27 , 29 ), one used polysomnographic recordings (PSG) ( 25 ), one used a brief questionnaire form of neuropsychiatric inventory (NPI-Q) ( 23 ), one used a rapid eye movement sleep behavior disorder screening questionnaire (RBDSQ) ( 30 ).…”

“…One region of interest (ROI)-based sMRI study found significant differences of posterior brain stem morphology in the AD and SLD group compared with controls and a negative correlation between the NPI scores and left posterior lateral brain stem volume ( 24 ), and another ROI study found decreased pineal gland volume in AD and SLD compared with AD, and the pineal gland volume negatively correlated with the severity of SLD ( 30 ). One whole brain and hippocampus subfield ROI study found decreased gray matter volume of bilateral cingulate gyrus in poor sleeper AD compared with AD only as well as no significant results in the hippocampus ( 27 ).…”

“…Degeneration of it could occur very early in patients with AD and also contribute to the onset of SLD, fragmented sleep, impaired memory consolidation, and cognitive decline (24). Some researchers believe that the pineal gland is associated with sleep regulation through melatonin synthesis, and betaamyloid could easily inhibit its function (39), which, in turn, could reduce the protection of cholinergic neurons from amyloid toxicity, increase the risk of both SLD and AD (30). In the included studies, only one found decreased pineal gland volume in the comorbidity group (30).…”

“…Some researchers believe that the pineal gland is associated with sleep regulation through melatonin synthesis, and beta-amyloid could easily inhibit its function ( 39 ), which, in turn, could reduce the protection of cholinergic neurons from amyloid toxicity, increase the risk of both SLD and AD ( 30 ). In the included studies, only one found decreased pineal gland volume in the comorbidity group ( 30 ). Another ROI-based study ( 28 ) and four whole-brain studies did not find any significant results ( 22 , 23 , 27 , 29 ).…”