scholarly journals Rest-Activity Pattern and Circadian Phase Alterations Across the Alzheimer’s Disease Clinical Spectrum

2021 ◽  
Vol 3 (4) ◽  
pp. 137-141
Author(s):  
Hyun Woong Roh ◽  
Sang Joon Son
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Activity Pattern ◽  
Comprehensive Evaluation ◽  
Disease Stage ◽  
Circadian Phase ◽  
Dementia Patients ◽  
Clinical Diagnoses ◽  
Rest Activity

Actigraphy-derived locomotor activity recordings are novel and critical tools for evaluating rest-activity pattern and circadian phase in humans. We conducted a narrative review assessing rest-activity pattern and circadian phase alterations within various stages of Alzheimer’s disease, in consideration of the reciprocal associations between neurodegeneration and circadian rhythm disruption in patients with Alzheimer’s disease. The goal of this review was to characterize possible associations between circadian rhythm disruption and neurodegeneration in Alzheimer’s disease. To the best of our knowledge, only two studies have assessed rest-activity pattern and circadian phase alterations in the preclinical Alzheimer’s disease stage and the results of the studies were inconsistent. Several studies have evaluated rest-activity pattern and circadian phase alterations in patients with Alzheimer’s dementia. The most replicated findings were delayed phase and increased activity fragmentation, represented as increased intra-daily variability. Unfortunately, many studies performed in dementia patients have not examined neuroimaging biomarkers or structured neuropsychological tests, thus limiting the specification of dementia clinical diagnoses. Future studies should consider a more comprehensive evaluation of various clinical and biomarker characteristics in patients with dementia or Alzheimer’s disease.

A Follow-Up Study of Actigraphic Measures in Home-Residing Alzheimer's Disease Patients

1998 ◽  
Vol 11 (1) ◽  
pp. 7-10 ◽  
Author(s):  
Jerome A. Yesavage ◽  
Leah Friedman ◽  
Helena C. Kraemer ◽  
Art Noda ◽  
Deryl Wicks ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Behavioral Disturbance ◽  
Nocturnal Sleep ◽  
Significant Deterioration ◽  
Cross Sectional ◽  
Sleep Parameters ◽  
Rest Activity

This article reports cross-sectional and follow-up data with actigraphic measures of nocturnal sleep and rest/activity in 61 Alzheimer's disease (AD) patients as well as the relation of actigraphic measures to levels of behavioral disturbance across different stages of the disease. Over the course of approximately 1.5 years' follow-up, patients showed significant deterioration of nocturnal sleep parameters, but no significant change in rest/activity circadian rhythm parameters. There were also significant correlations among nocturnal sleep, rest/activity circadian rhythm, and behavioral disturbance measures, but only in relatively early stages of AD. It is argued that study of nocturnal sleep and circadian rhythm in relation to behavioral disturbance in AD requires longitudinal data and analyses that take into account the stage of disease at which patients are assessed.

Effects of Melatonin in Two Individuals with Alzheimer's Disease

1998 ◽  
Vol 87 (1) ◽  
pp. 331-339 ◽  
Author(s):  
Girardin Jean-Louis ◽  
Ferdinand Zizi ◽  
Hans Von Gizycki ◽  
Harvey Taub
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Aging Process ◽  
Activity Rhythm ◽  
The Other ◽  
Beneficial Effects ◽  
Melatonin Administration ◽  
Activity Cycles ◽  
Rest Activity

Dementia has been associated with circadian rhythm disturbances expressed in several dimensions including body temperature, hormonal concentrations, sleep and wakefulness patterns, and rest-activity cycles. These disturbances may be the result of a dampening in the amplitude of the circadian rhythm. One of the symptoms associated with the aging process has been a decline in the amplitude of the melatonin rhythm. Here, the results of melatonin administration to two patients with Alzheimer's disease are presented. Melatonin administration enhanced and stabilized the circadian rest-activity rhythm in one of the patients along with some reduction of daytime sleepiness and an improvement in mood. The other patient, who was characterized by less cognitive impairment, showed no significant changes associated with melatonin ingestion. Interestingly, the acrophase of rest-activity was delayed for about one hour in both patients. These results suggest that melatonin may have beneficial effects in some patients with Alzheimer's disease

P2-087: Comprehensive evaluation of disruption of circadian rhythm of Alzheimer's disease: Interaction of polysomnography and physiology

2006 ◽  
Vol 2 ◽  
pp. S258-S258
Author(s):  
Kentaro Asayama ◽  
Meredith Olson ◽  
Neil W. Kowall ◽  
Edward G. Stopa ◽  
David G. Harper
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Comprehensive Evaluation

scholarly journals The circadian rest-activity pattern predicts cognitive decline among mild-moderate Alzheimer’s disease patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Adriano D. S. Targa ◽  
Iván D. Benítez ◽  
Faridé Dakterzada ◽  
John Fontenele-Araujo ◽  
Olga Minguez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Effect Size ◽  
Activity Pattern ◽  
Symptomatic Disease ◽  
Presymptomatic Stage ◽  
T Tau ◽  
Rest Activity

Abstract Background Alterations in circadian rhythms are present in the presymptomatic stage of Alzheimer’s disease (AD), possibly contributing to its pathogenesis. However, it is unknown whether such alterations are associated with worse outcomes once individuals are diagnosed with symptomatic disease. We aimed to evaluate the association between the circadian rest-activity pattern and AD-related features in patients with mild-moderate AD. Methods We assessed the circadian rest-activity pattern of consecutive patients with mild-moderate AD through actigraphy for 14 days. Cerebrospinal fluid was obtained to determine the levels of important pathological markers including amyloid-beta protein (Aβ42), phosphorylated tau (P-tau), total tau (T-tau), and neurofilament light (NF-L). Neuropsychological evaluation was conducted at the beginning of the study and after 12 months of follow-up. Linear regression models were performed considering the global population and Aβ42+ patients only. Results The cohort included 100 patients with mild-moderate AD. The median age [p25;p75] was 76.0 [73.0;80.0] years and 63.0% were female. Older age (effect size [SE] of 0.324 [0.096]; p = 0.001) and male sex (0.780 [0.193]; p = 0.001) were associated with increased fragmentation and decreased synchronization of the rhythm, respectively. After adjusting for age, sex, and season of the year, increased levels of T-tau (effect size [95% CI] of 0.343 [0.139 to 0.547]; p = 0.001) and NF-L (0.444 [0.212 to 0.676]; p = 0.001) were associated with a higher amplitude of the rest-activity rhythm. Increased fragmentation of the rhythm at baseline was associated with greater cognitive decline after one year of follow-up independent of age, sex, T-tau/Aβ42 ratio, educational level, and season of the year (− 0.715 [− 1.272 to − 0.157]; p = 0.013). Similar findings were obtained considering only the Aβ42+ patients. Conclusions Our results suggest a potential role of the circadian rest-activity pattern in predicting the cognitive decline of patients with mild-moderate AD. Further studies are warranted to confirm these findings and to elucidate whether there is causality among the observed associations.

scholarly journals Safety and Efficacy of Lemborexant in Patients With Irregular Sleep-Wake Rhythm Disorder and Alzheimer’s Disease Dementia: Results From a Phase 2 Randomized Clinical Trial

2020 ◽  
pp. 1-12
Author(s):  
M. Moline ◽  
S. Thein ◽  
M. Bsharat ◽  
N. Rabbee ◽  
M. Kemethofer-Waliczky ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Circadian Rhythm ◽  
Cognitive Function ◽  
The United States ◽  
Phase 2 ◽  
Rhythm Disorder ◽  
Alzheimer’S Disease Dementia ◽  
Rest Activity

BACKGROUND: Irregular sleep-wake rhythm disorder (ISWRD) is a common sleep disorder in individuals with Alzheimer’s disease dementia (AD-D). OBJECTIVES: This exploratory phase 2 proof-of-concept and dose-finding clinical trial evaluated the effects of lemborexant compared with placebo on circadian rhythm parameters, nighttime sleep, daytime wakefulness and other clinical measures of ISWRD in individuals with ISWRD and mild to moderate AD-D. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Sites in the United States, Japan and the United Kingdom. PARTICIPANTS: Men and women 60 to 90 years of age with documentation of diagnosis with AD-D and Mini-Mental State Exam (MMSE) score 10 to 26. INTERVENTION: Subjects were randomized to placebo or one of four lemborexant treatment arms (2.5 mg, 5 mg, 10 mg or 15 mg) once nightly at bedtime for 4 weeks. MEASUREMENTS: An actigraph was used to collect subject rest-activity data, which were used to calculate sleep-related, wake-related and circadian rhythm–related parameters. These parameters included least active 5 hours (L5), relative amplitude of the rest-activity rhythm (RA) and mean duration of sleep bouts (MDSB) during the daytime. The MMSE and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) were used to assess for changes in cognitive function. RESULTS: Sixty-two subjects were randomized and provided data for circadian, daytime and nighttime parameters (placebo, n = 12; lemborexant 2.5 mg [LEM2.5], n = 12; lemborexant 5 mg [LEM5], n = 13, lemborexant 10 mg [LEM10], n = 13 and lemborexant 15 mg [LEM15], n = 12). Mean L5 showed a decrease from baseline to week 4 for LEM2.5, LEM5 and LEM15 that was significantly greater than with placebo (all p < 0.05), suggesting a reduction in restlessness. For RA, LS mean change from baseline to week 4 versus placebo indicated greater distinction between night and day with all dose levels of lemborexant, with significant improvements seen with LEM5 and LEM15 compared with placebo (both p < 0.05). The median percentage change from baseline to week 4 in MDSB during the daytime indicated a numerical decrease in duration for LEM5, LEM10 and LEM15, which was significantly different from placebo for LEM5 and LEM15 (p < 0.01 and p = 0.002, respectively). There were no serious treatment-emergent adverse events or worsening of cognitive function, as assessed by the MMSE and ADAS-Cog. Lemborexant was well tolerated. No subjects discontinued treatment. CONCLUSIONS: This study provides preliminary evidence of the potential utility of lemborexant as a treatment to address both nighttime and daytime symptoms in patients with ISWRD and AD-D.

Microglia in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Patrick Süß ◽  
Johannes C.M. Schlachetzki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Amyloid Β ◽  
Disease Stage ◽  
Disease Modifying Therapy ◽  
Transcriptomic Signature

: Alzheimer’s Disease (AD) is the most frequent neurodegenerative disorder. Although proteinaceous aggregates of extracellular Amyloid-β (Aβ) and intracellular hyperphosphorylated microtubule- associated tau have long been identified as characteristic neuropathological hallmarks of AD, a disease- modifying therapy against these targets has not been successful. An emerging concept is that microglia, the innate immune cells of the brain, are major players in AD pathogenesis. Microglia are longlived tissue-resident professional phagocytes that survey and rapidly respond to changes in their microenvironment. Subpopulations of microglia cluster around Aβ plaques and adopt a transcriptomic signature specifically linked to neurodegeneration. A plethora of molecules and pathways associated with microglia function and dysfunction has been identified as important players in mediating neurodegeneration. However, whether microglia exert either beneficial or detrimental effects in AD pathology may depend on the disease stage. : In this review, we summarize the current knowledge about the stage-dependent role of microglia in AD, including recent insights from genetic and gene expression profiling studies as well as novel imaging techniques focusing on microglia in human AD pathology and AD mouse models.

scholarly journals Classifying Non-Dementia and Alzheimer’s Disease/Vascular Dementia Patients Using Kinematic, Time-Based, and Visuospatial Parameters: The Digital Clock Drawing Test

2021 ◽  
Vol 82 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Anis Davoudi ◽  
Catherine Dion ◽  
Shawna Amini ◽  
Patrick J. Tighe ◽  
Catherine C. Price ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Area Under The Curve ◽  
Clock Drawing Test ◽  
Digital Clock ◽  
Clock Drawing ◽  
Drawing Test ◽  
Dementia Patients ◽  
Optimal Area

Background: Advantages of digital clock drawing metrics for dementia subtype classification needs examination. Objective: To assess how well kinematic, time-based, and visuospatial features extracted from the digital Clock Drawing Test (dCDT) can classify a combined group of Alzheimer’s disease/Vascular Dementia patients versus healthy controls (HC), and classify dementia patients with Alzheimer’s disease (AD) versus vascular dementia (VaD). Methods: Healthy, community-dwelling control participants (n = 175), patients diagnosed clinically with Alzheimer’s disease (n = 29), and vascular dementia (n = 27) completed the dCDT to command and copy clock drawing conditions. Thirty-seven dCDT command and 37 copy dCDT features were extracted and used with Random Forest classification models. Results: When HC participants were compared to participants with dementia, optimal area under the curve was achieved using models that combined both command and copy dCDT features (AUC = 91.52%). Similarly, when AD versus VaD participants were compared, optimal area under the curve was, achieved with models that combined both command and copy features (AUC = 76.94%). Subsequent follow-up analyses of a corpus of 10 variables of interest determined using a Gini Index found that groups could be dissociated based on kinematic, time-based, and visuospatial features. Conclusion: The dCDT is able to operationally define graphomotor output that cannot be measured using traditional paper and pencil test administration in older health controls and participants with dementia. These data suggest that kinematic, time-based, and visuospatial behavior obtained using the dCDT may provide additional neurocognitive biomarkers that may be able to identify and tract dementia syndromes.

Circadian Rhythm Disturbance in Agitation of Alzheimer's Disease

2021 ◽  
Vol 29 (4) ◽  
pp. S111-S113
Author(s):  
John Outen ◽  
Adam Spira ◽  
Sarah Wanigatunga ◽  
Vadim Zipunnikov ◽  
Mark Wu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Rhythm Disturbance
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