title: Noninvasive fractal biomarker of clock neurotransmitter disturbance in humans with dementia.
abstract: Human motor activity has a robust, intrinsic fractal structure with similar patterns from minutes to hours. The fractal activity patterns appear to be physiologically important because the patterns persist under different environmental conditions but are significantly altered/reduced with aging and Alzheimer's disease (AD). Here, we report that dementia patients, known to have disrupted circadian rhythmicity, also have disrupted fractal activity patterns and that the disruption is more pronounced in patients with more amyloid plaques (a marker of AD severity). Moreover, the degree of fractal activity disruption is strongly associated with vasopressinergic and neurotensinergic neurons (two major circadian neurotransmitters) in postmortem suprachiasmatic nucleus (SCN), and can better predict changes of the two neurotransmitters than traditional circadian measures. These findings suggest that the SCN impacts human activity regulation at multiple time scales and that disrupted fractal activity may serve as a non-invasive biomarker of SCN neurodegeneration in dementia.
authors.affiliation: Medical Biodynamics Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States. khu@bics.bwh.harvard.edu
authors.forename: Kun
authors.initials: K
authors.lastname: Hu
authors.forename: David G
authors.initials: DG
authors.lastname: Harper
authors.forename: Steven A
authors.initials: SA
authors.lastname: Shea
authors.forename: Edward G
authors.initials: EG
authors.lastname: Stopa
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D001683:Biological Clocks; D015415:Biomarkers / Q000378:metabolism; D001831:Body Temperature; D002940:Circadian Rhythm; D003704:Dementia / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism; D009496:Neurotensin / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus; D014667:Vasopressins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents; D014667:Vasopressins; D009496:Neurotensin