Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease.

Importance: Circadian rhythm disturbances occur in symptomatic Alzheimer disease (AD) and have been hypothesized to contribute to disease pathogenesis. However, it is unknown whether circadian changes occur during the presymptomatic phase of the disease. Objective: To examine the associations between circadian function, aging, and preclinical AD pathology in cognitively normal adults. Design, Setting, and Participants: This cross-sectional study was conducted using community volunteers from the Knight Alzheimer's Disease Research Center at Washington University in St Louis. Cognitively normal participants (n = 205) underwent 7 to 14 days of actigraphy in their home environment between 2010 and 2012, in addition to clinical assessment, amyloid imaging with Pittsburgh Compound B (PiB), and cerebrospinal fluid biomarker collection. Data collected from 3 years before to 6 months after actigraphy were included. Sixteen participants were excluded owing to incomplete data collection. Main Outcomes and Measures: Circadian rhythm analysis was performed on actigraphy data using 3 methods: cosinor, nonparametric, and empirical mode decomposition. Preclinical AD was assessed by longitudinal clinical assessment, amyloid imaging with PiB, and cerebrospinal fluid biomarker collection. Results: Data from 189 participants were included in the analyses. The mean (SD) age was 66.6 (8.3) years, and 121 participants (64%) were women. Older age (ß = .247; P = .003) and male sex (ß = .170; P = .04), in the absence of amyloid pathology, were associated with a significant increase in intradaily variability, a nonparametric measure of rest-activity rhythm fragmentation, as well as decreased amplitude by several measures. After correction for age and sex, the presence of preclinical amyloid plaque pathology, assessed by positive PiB imaging (mean [SD], 0.804 [0.187] for PiB negative vs 0.875 [0.178] for PiB positive; P = .05) or increasing cerebrospinal fluid phosphorylated-tau to amyloid ß 42 ratio (ß = .231; P = .008), was associated with increased intradaily variability, indicating rest-activity rhythm fragmentation. Conclusions and Relevance: Preclinical AD is associated with rest-activity rhythm fragmentation, independent of age or sex. Aging was also associated with circadian dysfunction independently of preclinical AD pathology, particularly in men. The presence of circadian rhythm abnormalities in the preclinical phase of AD suggests that circadian dysfunction could contribute to early disease pathogenesis or serve as a biomarker of preclinical disease.

Night sleep influences white matter microstructure in bipolar depression.

BACKGROUND: Alteration of circadian rhythms and sleep disruption are prominent trait-like features of bipolar disorder (BD). Diffusion tensor imaging (DTI) measures suggest a widespread alteration of white matter (WM) microstructure in patients with BD. Sleep promotes myelination and oligodendrocyte precursor cells proliferation. We hypothesized a possible association between DTI measures of WM microstructure and sleep quantity measures in BD. METHODS: We studied 69 inpatients affected by a depressive episode in course of type I BD. We used whole brain tract-based spatial statistics on DTI measures of WM microstructure: axial, radial, and mean diffusivity (AD, RD, MD), and fractional anisotropy (FA). Self-assessed measures of time asleep (TA) and total sleep time (TST) were extracted from the Pittsburgh Sleep Quality Index (PSQI). Actigraphic recordings were performed on a subsample of 23 patients. RESULTS: We observed a positive correlation of DTI measures of FA with actigraphic measures of TA and TST, and with PSQI measure of TA. DTI measures of RD inversely associated with actigraphic measure of TA, and with PSQI measures of TA and TST. Several WM tracts were involved, including corpus callosum, cyngulate gyrus, uncinate fasciculus, left superior and inferior longitudinal and fronto-occipital fasciculi, thalamic radiation, corona radiata, retrolenticular part of internal capsule and corticospinal tract. LIMITATIONS: The study is correlational in nature, and no conclusion about a causal connection can be drawn. CONCLUSIONS: Reduced FA with increased RD and MD indicate higher water diffusivity associated with less organized myelin and/or axonal structures. Our findings suggest an association between sleep disruption and these measures of brain microstructure in specific tracts contributing to the functional connectivity in BD.

Systemic blood pressure profile correlates with cardiac 123I-MIBG uptake in patients with Parkinson's disease.

To examine the correlation between the systemic blood pressure profile and cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's disease (PD), we monitored circadian blood pressure patterns of 37 PD patients of 49 to 85 years of age (mean, 71.8±8.4 years) using a portable blood pressure monitoring device. The duration of PD was 0.5 to 15 years, and the disability level (modified Hoehn and Yahr stage) ranged from 1.0 to 4.0 (mean, 2.7±0.7). There were 37 age- and sex-matched control subjects. Cardiac MIBG scintigraphy was performed for the 37 PD patients. Based on the nocturnal fall in mean arterial blood pressure (MABP), we classified patients into extreme dippers (nocturnal reduction of MABP >20%), dippers (>10% but <20%), nondippers (<10% but >0%), and inverted dippers (<0%). Average 24-hour MABP values revealed reduced BP variability in PD patients. The percentage nocturnal fall in MABP was significantly different between PD patients and control subjects (p<0.05). Significant correlations were found between % MABP reduction and the heart-to-mediastinum (H/M) ratio on early and delayed images (p<0.01). The UPDR motor score, early and delay H/M ratios were also significantly different between patients who were and were not dippers (p<0.05). The present results reported for the first time a significant correlation between the systemic blood pressure profile and cardiac (123)I-MIBG uptake in patients with PD. The degeneration between the brainstem and the postganglionic neurons of myocardial sympathetic nerves may progress in parallel in patients with PD.