Neuroinflammation is proposed as one of the mechanisms by which Alzheimer’s disease pathology, including amyloid-β plaques, leads to neuronal death and dysfunction. Increases in the expression of markers of microglia, the main neuroinmmune cell, are widely reported in brains from patients with Alzheimer’s disease, but the literature has not yet been systematically reviewed to determine whether this is a consistent pathological feature. A systematic search was conducted in Medline, Embase and PsychINFO for articles published up to 23 February 2017. Papers were included if they quantitatively compared microglia markers in post-mortem brain samples from patients with Alzheimer’s disease and aged controls without neurological disease. A total of 113 relevant articles were identified. Consistent increases in markers related to activation, such as major histocompatibility complex II (36/43 studies) and cluster of differentiation 68 (17/21 studies), were identified relative to nonneurological aged controls, whereas other common markers that stain both resting and activated microglia, such as ionized calcium-binding adaptor molecule 1 (10/20 studies) and cluster of differentiation 11b (2/5 studies), were not consistently elevated. Studies of ionized calcium-binding adaptor molecule 1 that used cell counts almost uniformly identified no difference relative to control, indicating that increases in activation occurred without an expansion of the total number of microglia. White matter and cerebellum appeared to be more resistant to these increases than other brain regions. Nine studies were identified that included high pathology controls, patients who remained free of dementia despite Alzheimer’s disease pathology. The majority (5/9) of these studies reported higher levels of microglial markers in Alzheimer’s disease relative to controls, suggesting that these increases are not solely a consequence of Alzheimer’s disease pathology. These results show that increased markers of microglia are a consistent feature of Alzheimer’s disease, though this seems to be driven primarily by increases in activation-associated markers, as opposed to markers of all microglia.
The prevalence of Alzheimer's disease (AD) continues to rise, while treatment options for cognitive impairment are limited. Acetylcholinesterase inhibitors (AChEIs) aim to provide symptomatic benefit for cognitive decline, however these drugs are not without adverse events (AEs). The safety profile of each drug must be taken carefully into consideration before being prescribed, as new dosages and formulations have recently been approved. Areas covered: Donepezil, galantamine and rivastigmine are the three AChEIs approved for the treatment of varying stages of AD. Numerous clinical trials and post-marketing studies have evaluated the safety of these medications. This article will review the safety, efficacy and tolerability of these drugs in treating AD. Topics including pharmacovigilance databases, concomitant drug interactions, prescribing cascades, and treatment discontinuation are also covered. Expert opinion: AChEI use in those with mild, moderate or severe AD provide modest improvements in cognition, function and behavior. The pharmacological treatment of AD using AChEIs is associated with generally mild AEs. Differences in drug formulations should be taken into account when determining the most appropriate route of administration for each individual. Furthermore, discontinuation of AChEIs must be carefully monitored as it may be associated with worsening cognitive impairment.
BackgroundThe association between the weight of school bag and Low Back Pain (LBP) amongst students remains under intense debate worldwide. This study aimed to estimate the prevalence of LBP amongst public high school students (14 to 19 years) in Kuwait and to investigate the association between LBP and the weight of school bags.MethodsAn analytical cross-sectional study using multistage cluster random sampling with probability proportional to size was conducted on a total of 950 public high school students from all governorates. Data on LBP were collected through face-to-face interviews using a structured questionnaire. A 0–10 Numeric Pain Rating Scale was used to rate the intensity of LBP. The students’ height and weight in addition to the weight of their school bags were measured using appropriate weight and height scales. Logistic regression was used to investigate the association between the weight of school bags and LBP while adjusting for potential confounders.ResultsThe estimated lifetime, 6-month, and 1-month prevalence of LBP were 70.3% (95% CI: 67.30–73.21%), 49.1% (95% CI: 45.83–52.28%), and 30.8% (95% CI: 27.81–33.78%) respectively, with significantly higher prevalence amongst females compared to males (p < 0.001). The absolute weight of school bag was not significantly associated with LBP neither in univariable nor multivariable analysis. The relative weight of school bag (as a percentage of the body weight) was significantly associated with LBP in univariable analysis but not in multivariable analysis. The perceived heaviness of school bag, however, was found to be significantly associated with LBP throughout the analysis (p < 0.001).ConclusionIn conclusion, LBP amongst high school students in Kuwait seems to be very common with a prevalence resembling that of high-income countries. Our data suggest that the perceived heaviness of school bag is far more important than the actual bag weight. Current recommendations about the weight of school bags, which are not supported by evidence, should be revised to take into account the students’ perceived heaviness of school bag.
Apathy is a prevalent and problematic neuropsychiatric symptom in those with dementia that is emerging as a treatment target, necessitating accurate assessment. While many apathy scales are available, not all have been developed for use exclusively in dementia, and psychometric properties may vary across different populations. This systematic review aimed to provide an overview of the psychometric properties of apathy scales used in Alzheimer's disease (AD) and related dementias, as well as rate the methodological quality of supporting studies. In addition, for those scales identified, performance in clinical trials was reviewed. A search was conducted through Medline, Psychinfo, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Articles that reported psychometric properties of an apathy scale in an AD or mixed dementia population were included. Of 15 articles, the methodological quality ratings of the studies ranged from adequate to excellent. Three clinical trials and two pooled analyses of clinical trials were included that used apathy scales evaluated in this review. Three scales emerged. The Neuropsychiatric Inventory apathy subscale (NPI-apathy) and the Apathy Evaluation Scale (AES) had the greatest number of studies evaluating psychometric properties and were also used in the clinical trials and have shown sensitivity to change. The Dementia Apathy Interview and Rating demonstrated excellent values of internal consistency, validity, and reliability for use in an AD population. Future research should address comparative scale performance and assess ability to distinguish subtypes of apathy. Validation may include evaluation of performance against specific imaging defined deficits.
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