Relationship between Cognitive and Sleep-wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer's Disease

• Published in: Frontiers in aging neuroscience 2017-04, Vol.9, p.93-93
• Main Authors: Abulafia, Carolina, Duarte-Abritta, Bárbara, Villarreal, Mirta F, Ladrón-de-Guevara, María S, García, Celeste, Sequeyra, Geraldine, Sevlever, Gustavo, Fiorentini, Leticia, Bär, Karl-Jürgen, Gustafson, Deborah R, Vigo, Daniel E, Guinjoan, Salvador M
• Format: Article
• Language: English
• Subjects: actigraphy; Alzheimer's disease; Autonomic nervous system; Biomarkers; Body temperature; brain; Brain stem; cardiac autonomic control; Circadian rhythm; Circadian rhythms; circadian system; Cognitive ability; early diagnosis; Education; Family medical history; Heart; Heart rate; heart-rate-variability; Hypotheses; Individ och samhälle VIDSOC; Individual and Society VIDSOC; Laboratories; late-onset Alzheimer's disease; Middle age; Mutation; network; Neurodegeneration; Neurologi; Neurology; Neuropathology; Neuroscience; Offspring; Pathology; Psychiatry; Sleep; Sleep and wakefulness; state; tau; temperature; Wavelet transforms
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2017.00093

Early neuropathological changes characteristic of late-onset Alzheimer's disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 ± 0.4 vs. 8.6 ± 0.6, = 4.97, = 49, < 0.01) and language (Weschler's vocabulary 51.4 ± 1.3 vs. 44.3 ± 1.5, = 2.49, = 49, < 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 ± 0.47 h vs. 3.8 ± 0.26 h, = 2.48, = 40, = 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep-wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.