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No prior studies have evaluated the efficacy and safety of zolpidem and zopiclone to treat insomnia of demented patients. This randomized, triple-blind, placebo-controlled clinical trial used these drugs to treat patients with probable, late onset Alzheimer's dementia (AD) (DSM V and NINCDS-ADRDA criteria) exhibiting insomnia (DSM V criteria and nocturnal NPI scores ≥ 2). Actigraphic records were performed for 7 days at baseline and for 14 days during the treatment period in 62 patients aged 80.5 years in average and randomized at a 1:1:1 ratio for administration of zolpidem 10 mg/day, zopiclone 7.5 mg/day or placebo. Primary endpoint was the main nocturnal sleep duration (MNSD), whereas secondary outcomes were the proportion of the night time slept, awake time after sleep onset (WASO), nocturnal awakenings, total daytime sleep time and daytime naps. Cognitive and functional domains were tested before and after drug/placebo use. Three participants under zopiclone use had intervention interrupted due to intense daytime sedation and worsened agitation with wandering. Zopiclone produced an 81 min increase in MNSD (95% confidence interval (CI): -0.8, 163.2), a 26 min reduction in WASO (95% CI: -56.2, 4.8) and a 2-episode decrease in awakening per night (95% CI: -4.0, 0.4) in average compared to placebo. Zolpidem yielded no significant difference in MNSD despite a significant 22 min reduction in WASO (95% CI: -52.5, 8.3) and a reduction of 1 awakening each night (95% CI: -3.4, 1.2) in relation to placebo. There was a 1-point reduction in mean performance in the symbols search test among zolpidem users (95% CI: -4.1, 1.5) and an almost eight-point reduction in average scores in the digit-symbol coding test among zopiclone users (95% CI: -21.7, 6.2). In summary, short-term use of zolpidem or zopiclone by older insomniacs with AD appears to be clinically helpful, even though safety and tolerance remain issues to be personalized in healthcare settings and further investigated in subsequent trials. This trial was registered in ClinicalTrials.gov Identifier: NCT03075241.

Older adults have become a larger part of the driving population, but whether they are at increased risk of being involved in fatal crashes remains unclear. Methods We performed a systematic review of studies investigating fatal crash involvement of older vs non-older drivers by searching the following databases: PubMed, Cochrane Library, Embase, LILACS, SciELO, Web of Science, and ProQuest. Studies that used fatal crash involvement rates per distance driven as a measure of frequency were selected for meta-analysis. Results We analyzed 14 studies published between 2001 and 2018. Of these, 12 reported a higher rate of fatal crashes involving older drivers than non-older drivers; 9 of them used involvement rates per distance driven, which is considered the most appropriate metric. The meta-analysis revealed high heterogeneity between studies. The meta-regression attributed 40% of the heterogeneity to age (older vs non-older drivers) (p Conclusion Age appears to be associated with higher driver involvement rates for fatal crashes among older persons.

Aim The aim of this study was to test the efficacy and safety of mirtazapine in the treatment of sleep disorders in patients with Alzheimer's disease by means of a randomized, double-blind, placebo-controlled trial. Measurements were obtained for 7 days before intervention (baseline) and for 2 weeks after the onset of treatment. Methods Alzheimer's disease patients with sleep disorders (n = 24) received 15-mg mirtazapine (n = 8) or placebo (n = 16) once daily at 2100 hours for 2 weeks. Patients were evaluated with actigraphy and structured scales before and after intervention. Historical control was employed. Results Treatment with mirtazapine or placebo had no effect on cognitive and functional status as assessed by the Mini-Mental State Examination and the Katz scale, respectively. There were no differences between groups in the frequency or severity of the adverse events reported. Compared with the placebo group, mirtazapine users showed increased daytime sleepiness but no improvement in the duration or efficiency of nocturnal sleep after treatment. Conclusions This study showed no significant therapeutic effects of 15-mg mirtazapine in community-dwelling Alzheimer's disease patients with sleep disorders. Instead, this study found evidence of worsening of daytime sleep patterns.

A circadian rhythm is a cycle of approximately 24 h, responsible for many physiological adjustments, and ageing of the circadian clock contributes to cognitive decline. Rhythmicity is severely impaired in Alzheimer disease (AD) and few therapeutic attempts succeeded in improving sleep disorders in such context. This study evaluated sleep parameters by actigraphy in 30 AD patients before and after trazodone use for 2 weeks, and we show a significant improvement in relative rhythm amplitude (RRA), compatible with a more stable daytime behavioral pattern. So, trazodone appears to produce a stabilization of the circadian rhythms in individuals with AD.

Objectives There are no randomized clinical trials regarding efficacy of trazodone in the treatment of sleep disturbances (SD) in patients with Alzheimer disease (AD). We tested the efficacy and safety of trazodone to treat SD in patients with AD. Design We conducted a double-blind, randomized and controlled trial during periods of 7–9 days at baseline and 2 weeks of treatment. Setting Geriatric medical center of the university's general hospital. Participants Individuals with probable AD and SD. The complete analysis comprised 30 patients assigned to either the active treatment group (N = 15) or the placebo group (N = 15). Intervention Patients received 50 mg of trazodone once daily at 10:00 P.M. or placebo in a 1:1 ratio for 2 weeks. Measurements Patients were evaluated using actigraphy and structured scales before and after intervention. Results Compared with the placebo group, trazodone users slept 42.5 more minutes per night and had their nighttime percent sleep increased 8.5 percentage points according to actigraphic data post-treatment. Neither trazodone nor placebo induced significant daytime sleepiness or naps. The treatments with trazodone or placebo did not show any effects either on cognition (Mini-Mental State Examination, forward/backward digit span task, letter-number sequencing, arithmetic, digit symbol-coding, and symbol search) or functionality (Katz index). There were no differences in frequency or severity rating of adverse events between the groups. Conclusions This study shows significant therapeutic effects of trazodone 50 mg in community-dwelling AD patients with SD.

Aim The e4 alelle of the apolipoprotein E gene is known to be a key genetic risk factor for Alzheimer's disease and possibly for other neurological disorders. Some evidence in the literature indicates that the e4 allele interferes with human cognition independently of chronological age and diagnosis of Alzheimer's disease. The present study investigated the correlation of allelic variants of apolipoprotein E with the cognitive performance of elderly individuals without apparent cognitive impairment. Methods This was a cross-sectional analysis that included 213 non-demented elderly individuals (age ≥60 years) from the Brazilian Federal District. The analysis assessed the subjects for cognitive domains including short- and long-term episodic memory, processing speed, and attention and executive functions. Sociodemographic and other clinical characteristics were gathered and analyzed as covariates. Results Being sufficiently powered, the present study did not identify differential performance across apolipoprotein E genotypes. There was no influence of age, gender, marital status, schooling, depressive symptoms or use of central nervous system depressants when the analyses were controlled for such factors. Conclusions Our findings suggest that the e4 allele does not contribute to detectable cognitive decline within the context of non-dementia.

A 95-year-old woman had been treated over the past 8 years for progressive dysphagia. When her condition worsened, blood tests revealed the presence of leucocytosis and eosinophilia in the absence of anaemia or thrombocytopenia. Within 11 days of diagnosis, the patient died of respiratory failure. Necropsy showed normal thyroid tissue and an absence of infectious disease. However, an upper mediastinal tumour was found and was histopathologically diagnosed as a neoplastic transformation of the ectopic thyroid. Only 1% of endothoracic goitres present as ectopic or autonomous goitre with no parenchymal or vascular connection to the thyroid gland. This case represents a very rare situation in which a leukemoid reaction and peripheral hypereosinophilia were observed as a manifestation of an anaplastic thyroid carcinoma in an ectopic mass.

Sleep disorders (SD) in patients with dementia are very common in clinical practice. The use of antidepressants with hypnotic actions, such as trazodone, plays an important role in these cases. The aim of this study is to present a profile of the use of trazodone in demented patients with SD, as well as a review of trazodone hydrochloride in SD. We evaluated 178 elderly patients with Alzheimer’s disease and other dementias, clinically presenting SD and treated with hypnosedative medications. In the one-year period comprising the study, 68 (38.2%) of the 178 had sleep disorders. Most patients (114; 64%) had a diagnosis of Alzheimer’s disease. Approximately 85% of patients with SD used hypnosedative drugs. Trazodone was the most commonly used drug among patients (N = 35), with an effectiveness of 65.7%. Trazodone has been shown to be a good option for treatment of the elderly with dementia and associated SD. _________________________________________________________________________________________________________________ RESUMO Distúrbios do sono (DS) em pacientes com demência são muito comuns na prática clínica. O uso de antidepressivos com ação hipnótica, como a trazodona, tem um papel importante nesses casos. O objetivo desse estudo é apresentar um perfil do uso da trazodona em pacientes com demência e com DS, bem como revisar o cloridrato de trazodona no DS. Nós avaliamos 178 idosos com doença de Alzheimer (DA) e outras demências, clinicamente apresentando DS e que foram tratados com medicações hipnossedativas. No período de um ano de estudo, 68 (38,2%) tiveram DS. A maioria (114; 64%) tinham diagnóstico de DA. Aproximadamente 85% usaram fármacos hipnossedativos. A trazodona foi a mais utilizada (N=35), com evidência de melhora de 65,7%. A trazodona mostrou-se ser uma boa opção no tratamento de idosos com demência e DS associado.

The treatment of apathy is often complicated and difficult. The authors present a case of apathy syndrome that was treated successfully with modafinil. An 87-year-old widowed Brazilian woman presented with loss of interest and pleasure in activities. Her level of apathy, as evaluated by the Brazilian care giver version of the apathy scale, was 25 (a score higher than 18 points is associated with an apathy syndrome). No diagnosis of depression or sleep disorder was noted. After 2 years with many different antidepressants, modafinil treatment was started at 100 mg/day. One month after the initiation of modafinil therapy, the patient reported feeling more motivation, and she also returned to her favorite physical activity, which was swimming (400 m/day). Apathy scale revealed an improvement (18 points). Actigraphic analysis was performed, and no sleep disturbances were noted before or after treatment. Modafinil may be a promising option in the treatment of apathy.