Characterizing sleep problems in persons with Alzheimer's disease and normal elderly

We retrospectively analyzed sleep disturbance symptoms and estimated time in bed from the intake interviews of 399 healthy, non-demented elderly (NDE) and 263 persons with a diagnosis of possible (n = 53) or probable (n = 210) Alzheimer's disease (AD). Our primary objective was to identify what symptoms might underlie an individual's perception of 'sleep problems' and to determine if these were consistent within, and across, our two cohorts. We stratified each cohort according to whether or not they (or their caregiver) indicated that they had a 'sleep problem', and compared the frequency and endorsement rates of each of 21 sleep disturbance symptoms across those who did or did not endorse 'sleep problem'. For less than half of the symptoms in persons with AD, and a quarter of those in NDE, endorsement rates were significantly different depending on whether the reporter (or their sleep partner) did or did not report a sleep problem. Differences in mean frequency ratings between individuals reporting sleep problems relative to those not reporting were observed on 10 symptoms in both cohorts; six of these were the same symptom for both cohorts. When persons with subjective sleep problems in the AD and NDE cohorts were compared, only four of 21 symptoms were endorsed in one and not the other; two symptoms were significantly more frequent in one cohort than the other. Thus, within cohorts, the differences between persons with and without 'sleep problems' were relatively pronounced while the main differences in specific sleep-related symptoms between AD and NDE were not. Observed between-cohort differences appear to be driven by who is reporting, and the high prevalence of daytime sleeping in AD. Within-cohort differences reflect a clear distinction between persons with and without sleep problems, regardless of the reporter.     

The Sleep Disorders Inventory: an instrument for studies of sleep disturbance in persons with Alzheimer's disease

The Sleep Disorders Inventory (SDI) is an expanded version of one item of the Neuropsychiatric Inventory (NPI). It describes the frequency, severity, and caregiver burden of sleep-disturbed behaviors during a period prior to its administration. We carried out post hoc analyses on baseline responses to the SDI in 104 persons with Alzheimer's disease (AD) and live-in caregivers who had been recruited for a trial of melatonin in the treatment of sleep disturbance. These patient-participants averaged <7 h of sleep per night, measured by actigraph (sleep disturbance), for the 2-3-week period prior to administration of SDI. Data were from the 2 weeks prior to the baseline visit (SDI, NPI) including actigraph-derived sleep variables and 2 weeks' worth of sleep quality ratings (SQR) kept in a diary by caregivers, plus Mini-Mental State Examination and activities of daily living assessment at baseline. The prevalence of sleep disorder symptoms ranged from 34% (waking up at night thinking it is daytime) and 82% (getting up during the night). Worse SDI scores were associated with worse cognitive, functional, and behavioral status, but not with sex, age, education or duration of dementia. SDI scores were significantly worse in individuals meeting independently established criteria for a diagnosis of 'sleep disturbance' (<6 h total sleep time per night) whereas demographic variables and scores reflecting cognition and function were not significantly different across this grouping. The SDI covers a wide range of sleep behaviors and provides information independent of sleep time and SQR.     

Symposium: Cognitive processes and sleep disturbances: Sleep/wake patterns in Alzheimer's disease: relationships with cognition and function

SUMMARY  Alzheimer's disease (AD), the most common dementing disorder of aging, is a progressive neurodegenerative disease of unknown etiology. Two of the common clinical features of AD are progressive cognitive and functional impairment, and disturbed sleep/wake patterns. We examined sleep/wake patterns and cognitive and functional status measures in a large sample of AD subjects ranging from mild to moderate-severe in impairment. All subjects survived at least 2 years after initial diagnosis. Regression analyses revealed that sleep/wake variables were highly correlated with and explained significant variance in cognitive and functional measures. More wakefulness during the night and longer REM latencies were associated with impaired cognition and function while more REM and slow-wave sleep were associated with preserved cognition and function. These results indicate that with advancing severity of the disease, sleep/wake patterns are disrupted in parallel with the disturbances in cognition and function that are the hallmarks of AD. Further, they suggest that the neural substrates underlying each process degenerate at somewhat comparable rates.     

Changes in sleep theta rhythm are related to episodic memory impairment in early Alzheimer's disease

Impairments have been reported both in sleep structure and episodic memory in Alzheimer's disease [AD]. Our objective was to investigate the relationships between episodic memory deficits and electro-encephalography [EEG] abnormalities occurring during sleep in patients with early AD. Postlearning sleep was recorded in 14 patients with mild to moderate AD, and 14 healthy elderly controls after they performed an episodic memory task derived from the Grober and Buschke's procedure. For each sleep stage, the relative power and mean frequency in each band were analyzed. Relative to agematched controls, AD patients presented faster mean theta frequency in both REM sleep and slow wave sleep [SWS]. In AD patients, a correlative analysis revealed that faster theta frequency during SWS was associated with better delayed episodic recall. We assume that increased theta activity reflects changes in neuronal activity to maintain memory performance, indicating that compensatory mechanisms already described at the waking state could also be engaged during SWS.     

Disagreement between subjective and actigraphic measures of sleep duration in a population-based study of elderly persons

Sleep duration is an important concept in epidemiological studies. It characterizes a night's sleep or a person's sleep pattern, and is associated with numerous health outcomes. In most large studies, sleep duration is assessed with questionnaires or sleep diaries. As an alternative, actigraphy may be used, as it objectively measures sleep parameters and is feasible in large studies. However, actigraphy and sleep diaries may not measure exactly the same phenomenon. Our study aims to determine disagreement between actigraphic and diary estimates of sleep duration, and to investigate possible determinants of this disagreement. This investigation was embedded in the population-based Rotterdam Study. The study population consisted of 969 community-dwelling participants aged 57-97 years. Participants wore an actigraph and kept a sleep diary for, on average, six consecutive nights. Both measures were used to determine total sleep time (TST). In 34% of the participants, the estimated TST in the sleep diaries deviated more than 1 h from actigraphically measured TST. The level of disagreement between diary and actigraphic measures decreased with subjective and actigraphic measures of sleep quality, and increased with male gender, poor cognitive function and functional disability. Actigraphically measured poor sleep was often accompanied by longer subjective estimates of TST, whereas subjectively poor sleepers tended to report shorter TST in their diaries than was measured with actigraphy. We recommend, whenever possible, to use multiple measures of sleep duration, to perform analyses with both, and to examine the consistency of the results over assessment methods.     

Daytime sleepiness in mild and moderate Alzheimer's disease and its relationship with cognitive impairment

The increased tendency to fall asleep during the daytime together with increased wakefulness during the night has been demonstrated in patients with advanced Alzheimer's disease (AD). The aim of this study was to assess daytime sleep propensity in a cohort of patients with mild/moderate AD and to correlate it with cognitive impairment. Twenty drug-free AD patients meeting the NINCDS-ADRDA criteria for probable AD were evaluated. According to their Clinical Dementia Rating scores, subjects were classified into mild (CDR1; n=11) and moderate (CDR2; n=9) dementia patients. A group of 12 healthy subjects was taken as controls. The subjects were evaluated by the multiple sleep latency test (MSLT) after their nocturnal sleep pattern had been assessed by a polysomnographic recording throughout the night before. Both groups of AD patients showed a higher level of daytime sleepiness, which was statistically significant for mean daytime sleep latency (MDSL) (controls versus CDR1 and versus CDR2, CDR1 versus CDR2) and for 10:00 and 12:00 hour naps (controls versus CDR1, controls versus CDR2). In the entire group of AD patients, MDSL was significantly related with MMSE, De Renzi's Token test, verbal fluency, verbal digit span, story recall, Raven's Progressive Matrices, Weigl test and Benton's three-dimensional test. These data indicate that an increased sleep propensity during daytime occurs also in patients with mild/moderate AD detected by objective neurophysiological techniques.     

Characterization of sleep habits and medication outcomes for sleep disturbance in children and adults with Angelman syndrome

The objectives of this study were to characterize the sleep habits of 50 clinically referred individuals with Angelman syndrome (AS) and to retrospectively compare the effectiveness/tolerability of the three most commonly prescribed sleep medications in the sample. An experienced physician assigned a Clinical Global Impressions‐Severity scale (CGI‐S) score for each subject's AS‐specific symptoms. Caregivers completed the Child Sleep Habits Questionnaire (CSHQ; screen for sleep problems in school‐aged [4–10 years] children), a screening assessment for sleep problems. Caregivers provided information about medication trials targeting disturbed sleep, with the physician assigning a CGI‐Improvement scale (CGI‐I) score for each trial. Linear regression showed significant negative association between age and CSHQ score. In their lifetime, 72% of participants had taken a medication for sleep, most commonly melatonin, clonidine and trazodone. The majority continued these for 6 months or longer. With these medications, many demonstrated significant improvement in sleep disturbances, with no difference in odds of improvement between medications. Disturbed sleep was common in this cohort and significantly worse in younger‐aged participants. The majority received at least one medication trial for disturbed sleep and each of the most commonly prescribed medication was effective for a substantial percentage of participants. Most participants remained on medication for at least 6 months, suggesting favorable tolerability.     

线粒体与阿尔茨海默病

随着人类社会老龄化步伐的加快 ,老年人口所占比例逐渐增加 ,老年性痴呆的发病人数随年龄的增高而增多。阿尔茨海默病 (Ａｌｚｈｅｉｍｅｒ’ｓｄｉｓｅａｓｅ ,ＡＤ)作为老年性痴呆的一种重要类型 ,是中枢神经系统的一种渐进性退行性疾病 ,临床上以认知能力下降、记忆损害和痴呆为主要特征 ,神经病理上以脑细胞内神经纤维缠结 (ＮＦＴｓ)和细胞外老年斑 (ＳＰｓ)为主要特征 ,其中ＮＦＴ的主要成分为高度磷酸化的ｔａｕ蛋白 ,ＳＰｓ的主要成分为淀粉样蛋白前体 (ＡＰＰ)产生的β淀粉样肽 (Ａβ)。目前 ,ＡＤ的病因研究较多 ,其中线粒体因在…     

Gender differences in the cognitive impairment in Alzheimer's disease

Summary Introduction: There is evidence for gender differences in cognitive functioning. Men and women with Alzheimer's disease (AD) might also differ in the pattern of cognitive deficits. We hypothesised that gender differences in the cognitive deficits of Alzheimer's disease may be related to pre-existing gender differences in cognitive functioning. Method: The performances of 84 subjects with AD and 438 non-demented elderly, using the structured interview for the diagnosis of dementia of the Alzheimer type, multi-infarct dementia and dementias of other aetiology according to ICD-10 and DSM-III-R (SIDAM), were investigated. Subscores for different cognitive functions were compared between men and women. Confounding variables, i.e. age, degree of cognitive impairment, level of education, presence of lifetime diagnosis of major depression and of recent depressive symptoms, were accounted for by multiple regression analyses. Results: Non-demented elderly women had inferior visuoconstructive skills than men. In agreement, women with Alzheimer's disease also had inferior visuoconstructive skills, but in addition they tended to perform worse in items for intellectual abilities than men. Conclusion: Women seem to have minor weaknesses in spatial thinking compared to men. This may explain the inferior test results of non-demented and demented women in visuoconstructive tasks. However, our data also give some evidence for additional domain specific gender differences of cognitive impairment of AD that could not be observed in non-demented elderly, i.e. inferior test results in items for intellectual abilities in demented women compared with demented men. Gender differences in the neurodegenerative process of AD may add to gender differences in domain specific cognitive impairment. Further research on this topic is needed.     

Processing of semantic relations in normal aging and Alzheimer's disease.

The decline in semantic memory observed in Alzheimer's disease is presumed to result from progressive loss of the attributes underlying category representation. Here, we explored the possibility that semantic deterioration would affect attributes differently, depending on the type of semantic relationship connecting the subject and the object of the attribution. We compared the performance of 50 patients with probable Alzheimer's disease (APs) to that of 30 elderly controls in two semantic tasks: a verbal sentence verification task and a visual test of analogical relations, both including several types of semantic relations. On the sentence verification task, the performance of APs was comparable to that of elderly controls when statements were true, but deteriorated significantly when statements were false. This result was interpreted as a failure of controlled processes to successfully search semantic space when statements were incongruent or false. In addition, all participants found some semantic relations more difficult to process than others, with relative difficulty being consistent across tasks. Taxonomic semantic relations were the most difficult, while part/whole relations were the easiest, but also the ones to deteriorate most rapidly. In contrast, functional attributes were comparatively preserved as the disease progressed. These results emphasize the role of attention and semantic context in jointly determining access to relevant attributes and categories. Furthermore, they suggest that semantic memory impairments in Alzheimer's are affected by the type of processing and semantic relationship required by the task.     

Alzheimer基因研究现状

阿尔茨海默病(AD)目前临床无客观性生化检测手段,仅靠精神量表,且常在临床症状出现后才能诊断。近年来,一系列新的基因研究有助于阿尔茨海默病的早期识别。这些基因的改变往往先于阿尔茨海默病的病理变化和临床表现,对其早期诊断有重要意义。本文就这些基因的研究现状作一综述。     

Psychometric properties and cultural adaptation of sleep disturbance measures in Arabic‐speaking populations: A systematic review

The aim of this review was to evaluate the psychometric properties and cross‐cultural adaptation of sleep disturbance scales that have been translated into Arabic or originally developed in Arabic, and to identify appropriate scales that can be used in research and clinical practice intended for Arabic‐speaking participants. The following databases were searched: CINAHL (2003–2019), MEDLINE (1946–2019), EMBASE (1980–2019), PsycINFO (1806–2019) and Cochrane Library (1806–2019). This review was conducted following PRISMA guidelines. Terwee et al. (J. Clin. Epidemiol., 60, 2007, 34) quality assessment was used to evaluate the psychometric properties of the studies, and cross‐cultural adaptation was assessed using criteria from Guillemin, Bombardier, and Beaton (J. Clin. Epidemiol., 46, 1993, 1417). Seven studies met the inclusion criteria, which included four scales: the Epworth Sleepiness Scale, Insomnia Severity Index, Pittsburgh Sleep Quality Index, and Arabic Scale of Insomnia. Cross‐cultural adaptations scored between good and poor; psychometric properties information was missing for most scales. The review suggested that Pittsburgh Sleep Quality Index may be a useful scale to measure sleep disturbance, as the scale showed good cultural adaptation and acceptable psychometric properties in an Arabic population. Furthermore, the scales measure seven different aspects of sleep quality. This review provides options to help researchers and clinicians select the most appropriate instrument for their practice. Further psychometric testing and cultural adaptation is required for sleep scales used in Arabic clinical populations to ensure validity and reliability in outcome measurement for research studies.     

Chromosome fragility in Alzheimer's disease

We present cytogenetic findings for 12 patients with Alzheimer's Disease (AD) mean age 75.8 ± 6.01 years and 35 normal age and sex matched controls (mean age 74.8 ± 4.04 years). The study, undertaken due to reports of increased fragments and chromosome breakage in individuals with AD, was performed blind on coded peripheral blood specimens and the allocation of AD or control was not known to the cytogenetic staff until the end of the study. Both the AD group and the controls have been very carefully selected and both underwent the same clinical assessment and screening procedures which included CT scanning.
Chromosomes were analysed after 72 h cultures, using deprived medium TC199 which is known to enhance the appearance of fragile sites. A minimum of 50 cells was examined in each case and any rearrangement found was classified as ctg, csg, ctb, csb and the chromosome in which it occurred was recorded. Analysis of results showed that there was no statistically significant difference between the AD group and the controls for either the total occurrence of breaks, the type of aberration or the chromosome(s) involved. In both groups the commonest break was in 3p.     

阿尔茨海默病和血管性痴呆的精神行为症状比较

目的:探讨阿尔茨海默病(AD)和血管性痴呆(VaD)患者精神行为症状(BPSD)特点及其诊断价值。方法:用AD病理行为评分表(BEHAVE-AD)对40例AD和42例VaD患者进行评定。结果:两组患者BPSD总发生率和BE-HAVE-AD总分差异均无统计学意义(P>0.05)。AD组行为紊乱、攻击行为发生率(分别为45%与50%)及严重程度(评分分别为6.08±0.90分,4.60±1.27分),高于VaD组(发生率分别为16.67%与23.81%,严重程度评分分别为5.69±1.70分,3.50±1.58分),差异具有统计学意义(P<0.05);VaD组的情感障碍发生率(64.29%)及严重程度(3.52±0.85分)高于AD组(42.50%,2.53±1.23分),差异具有统计学意义(P<0.05)。结论:AD与VaD患者的精神行为症状呈现不同的特点,AD患者行为紊乱、攻击行为表现突出,VaD患者情感障碍表现突出。     

Unexpected survival advantage in elderly people with moderate sleep apnoea

Sleep‐disordered breathing is much more prevalent in elderly people than in middle‐aged or young populations, but its clinical significance in this age group is unclear. This study investigated retrospectively the rates of all‐cause mortality in elderly people (≥ 65 years) with a laboratory diagnosis of sleep apnoea, and compared their rates of mortality with that of age‐, gender‐ and ethnicity‐matched national mortality data. Survival of 611 elderly people was ascertained after a follow‐up of 5.17 ± 1.13 years. Their age was 70.4 ± 4.8 years, body mass index 30.4 ± 5.9 kg m^?2 and respiratory disturbance index (RDI) 28.9 ± 20.1 events h^?1. Seventy‐five (12.27%) patients died during the follow‐up period. In comparison with the demographically matched cohort from the general population, the standardized mortality rate of the sleep laboratory cohort was 0.67 [95% confidence interval (CI): 0.53–0.88; χ² = 11.69, P < 0.0006]. When calculated separately for patients with RDI < 20 (no/mild apnoea), RDI 20–40 (moderate apnoea) and RDI > 40 events h^?1 (severe apnoea) there was a significant survival advantage for the moderate group with a standardized mortality rate of 0.42 (P < 0.0002), while elderly people with no/mild apnoea tended to have lower mortality and those with severe sleep apnoea had the same mortality as the matched population cohorts. Cox regression analysis revealed that sleep latency and comorbidities but not sleep apnoea severity were associated independently with mortality. The survival advantage of elderly people with moderate sleep apnoea, combined with recent findings on the potential cardioprotective effects of chronic intermittent hypoxia, raise the possibility that apnoeas during sleep may activate adaptive pathways in the elderly.     

SRSS对13273名正常人睡眠状态的评定分析

目的　维护和促进人们的心理健康 ,制定一个标准化睡眠状况评定工具和适合中国人的常模。方法　采用 self- rating scale sleep of(SRSS)对不同年龄、不同性别、不同职业的人群进行标准化评定。结果　 1 32 73名正常人的总分值为 2 2 .1 4± 5.48,男女总分均值分别为2 2 .0 0± 5.47和 2 2 .2 7± 5.51 ,并计算出 1 0个因子和不同年龄均值的标准差。结论　总分和因子分均值可作为中国人睡眠状况的常模比较与参考     

Chromosome 12 and late-onset Alzheimer's disease

Alzheimer's disease is a complex neurodegenerative disorder, characterized by cognitive decline and distinctive neuropathology. Using large extended families with multiple affected, we found that three markers on chromosome 12 were linked with late-onset Alzheimer's disease. These markers were downstream from the gene for alpha-2 macroglobulin. It is likely that multiple genes will be identified either as risk factors or as causative agents for late-onset Alzheimer's disease.     

阿尔茨海默病的免疫治疗研究新进展

阿尔茨海默病（AD）是痴呆最常见的原因。根据淀粉样蛋白级联假说,AD的疫苗治疗成为该病的治疗方法。虽然AD的主动免疫治疗的Ⅱ期临床试验由于一些病人出现了脑膜脑炎而停止,但被治疗病人的临床和病理研究都表明疫苗治疗是有效的。为了避免AB疫苗诱发的脑膜脑炎,研究者试偿了各种各样的方法,其中包括发展短的免疫原、使用新的佐剂、改变给药途径、研制DNA非病毒载体的疫苗和应用催化性抗体。一些在转基因小鼠上的实验研究表明,上述的方法是AD的安全有效的治疗方法。