Sleep Quality and Preclinical Alzheimer Disease

JAMA neurology 03/2013; 70(5):1-7. DOI: 10.1001/jamaneurol.2013.2334
Source: PubMed


IMPORTANCE Sleep and circadian problems are very common in Alzheimer disease (AD). Recent animal studies suggest a bidirectional relationship between sleep and β-amyloid (Aβ), a key molecule involved in AD pathogenesis. OBJECTIVE To test whether Aβ deposition in preclinical AD, prior to the appearance of cognitive impairment, is associated with changes in quality or quantity of sleep. DESIGN Cross-sectional study conducted from October 2010 to June 2012. SETTING General community volunteers at the Washington University Knight Alzheimer's Disease Research Center. PARTICIPANTS Cognitively normal individuals (n = 145) 45 years and older were recruited from longitudinal studies of memory and aging at the Washington University Knight Alzheimer's Disease Research Center. Valid actigraphy data were recorded in 142. The majority (124 of 142) were recruited from the Adult Children Study, in which all were aged 45 to 75 years at baseline and 50% have a parental history of late-onset AD. The rest were recruited from a community volunteer cohort in which all were older than 60 years and healthy at baseline. MAIN OUTCOME MEASURES Sleep was objectively measured using actigraphy for 2 weeks. Sleep efficiency, which is the percentage of time in bed spent asleep, was the primary measure of sleep quality. Total sleep time was the primary measure of sleep quantity. Cerebrospinal fluid Aβ42 levels were used to determine whether amyloid deposition was present or absent. Concurrent sleep diaries provided nap information. RESULTS Amyloid deposition, as assessed by Aβ42 levels, was present in 32 participants (22.5%). This group had worse sleep quality, as measured by sleep efficiency (80.4% vs 83.7%), compared with those without amyloid deposition, after correction for age, sex, and APOE ϵ4 allele carrier status (P = .04). In contrast, quantity of sleep was not significantly different between groups, as measured by total sleep time. Frequent napping, 3 or more days per week, was associated with amyloid deposition (31.2% vs 14.7%; P = .03). CONCLUSIONS AND RELEVANCE Amyloid deposition in the preclinical stage of AD appears to be associated with worse sleep quality but not with changes in sleep quantity.

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Available from: David M Holtzman, Jul 14, 2014
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    • "d Abnormal circadian locomotor and core-body temperature rhythms d Suprachiasmatic d Vasopressin d Neurotensin d VIP Harper et al., 2001, 2008; Hu et al., 2013; van Someren et al., 1996 Sleep d Fragmented sleep pattern and reduced sleep time d EEG changes d Intermediate nucleus (ventrolateral preoptic area) d Lateral area d Galanin d Orexin d MCH Ju et al., 2013; Liguori et al., 2014; Lim et al., 2014; Prinz et al., 1982; Schmidt et al., 2013 "
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    ABSTRACT: Alzheimer's disease (AD) is increasingly recognized as a complex neurodegenerative disease beginning decades prior to the cognitive decline. While cognitive deficits remain the cardinal manifestation of AD, metabolic and non-cognitive abnormalities, such as alterations in body weight and neuroendocrine functions, are also present, often preceding the cognitive decline. Furthermore, hypothalamic dysfunction can also be a driver of AD pathology. Here we offer a brief appraisal of hypothalamic dysfunction in AD and provide insight into an underappreciated dual role of the hypothalamus as both a culprit and target of AD pathology, as well as into new opportunities for therapeutic interventions and biomarker development.
    Cell metabolism 09/2015; DOI:10.1016/j.cmet.2015.08.016 · 17.57 Impact Factor
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    • "In addition, for future studies, it would be important to consider sleep habits, as we know that poor sleep quality in the preclinical phase of AD is associated with aggregates of amyloid-␤ peptide, which is characteristic of this type of dementia [59]. "
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    ABSTRACT: Only a limited number of studies have investigated the decline of discrete cognitive domains as individuals progress from mild cognitive impairment (MCI) to dementia. Thus, the goal of this longitudinal study was to evaluate the cognitive changes underway during the years preceding a diagnosis of probable Alzheimer's disease (AD), and to compare these changes to those found in MCI participants who do not progress to dementia. Participants were compared as a function of whether they later converted to AD (n = 47) or not (n = 74). Cognitive change was assessed prior to the conversion year, using that year as a starting point. A combination of polynomial regression analyses and mixed ANOVAs assessed 1) the trajectory of cognitive decline for each domain and 2) the differences between non-progressors and those who had converted to AD. The different cognitive domains demonstrated very different patterns of decline in the group of MCI progressors. A quadratic function, i.e., many years of stable performance followed by a rapid decline just prior to diagnosis, was observed for delayed recall, working memory, and spatial memory. In contrast, a gradual linear decline was observed for immediate recall, executive function, and visuo-spatial abilities. Finally, language in progressors was impaired on all time periods relative to non-progressors, but there was no further change between the first assessments and conversion to AD. Individuals with MCI who progress to AD show abnormal cognition at least two years prior to their dementia diagnosis. The pattern of symptom change observed appears to depend upon the cognitive domain and thus, clinical studies should not assume similar rate of decline across domains. In contrast and, apart from verbal memory, the non-progressors present a performance similar to that of healthy older adults.
    Journal of Alzheimer's disease: JAD 08/2015; 47(4):901-913. DOI:10.3233/JAD-142910 · 4.15 Impact Factor
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    • "In AD, both sleep and circadian dysfunction are commonly reported. While sleep disturbances in AD are beyond the scope of this discussion and have been reviewed elsewhere (Ju et al., 2014; Peter-Derex et al., 2014), it is important to mention that subtle sleep disturbances appear to occur early in the disease process and may predict amyloid-beta (Aβ) plaque pathology and precede subsequent development of clinical dementia (Ju et al., 2013; Lim et al., 2013a; Spira et al., 2013). Disrupted circadian rhythms in activity, physiologic parameters, and melatonin secretion have been reported in AD reported by several groups (Witting et al., 1990; Skene and Swaab, 2003; Hatfield et al., 2004; Wu et al., 2006; Hu et al., 2009; Coogan et al., 2013). "
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    ABSTRACT: Disturbance of the circadian system, manifested as disrupted daily rhythms of physiologic parameters such as sleep, activity, and hormone secretion, has long been observed as a symptom of several neurodegenerative diseases, including Alzheimer disease. Circadian abnormalities have generally been considered consequences of the neurodegeneration. Recent evidence suggests, however, that circadian disruption might actually contribute to the neurodegenerative process, and thus might be a modifiable cause of neural injury. Herein we will review the evidence implicating circadian rhythms disturbances and clock gene dysfunction in neurodegeneration, with an emphasis on future research directions and potential therapeutic implications for neurodegenerative diseases.
    Frontiers in Pharmacology 02/2015; 6:29. DOI:10.3389/fphar.2015.00029 · 3.80 Impact Factor
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