The mechanism of γ-Secretase dysfunction in familial Alzheimer diseaseMutations in presenilin (PSEN) and amyloid precursor protein (APP) cause dominant early-onset Alzheimer's disease (AD), but the mechanism involved is debated. Here, such mutations are shown to alter γ-secretase activity, leading to changes in Aβ peptide cleavage patterns.

Purpose: Insomnia is highly prevalent in older persons and significantly impacts quality of life, functional abilities and health status. It is frequently treated with benzodiazepines or Z-drugs. Due to adverse events, an increased use of alternative sedative medications has been observed in older adults.We aimed to study the efficacy and safety of alternative sedative medications for treating insomnia in older people, excluding benzodiazepines and Z-drugs. Methods:We conducted a systematic search of MEDLINE (Pubmed), EMBASE and the Cochrane Central register of Controlled Trials databases. We included randomized controlled trials and prospective and retrospective quasi-experimental studies, conducted in patients older than 65 years, without psychiatric or neurological comorbidities. Results:The systematic search yielded 9483 articles, of which 24 were included in this review, describing nine different sleep medications in total. No clear beneficial impact on sleep could be demonstrated in studies investigating the impact of melatonin (n=10), paroxetine (n=1), diphenhydramine (n=1), tiagabine (n=2) and valerian (n=1). Ramelteon slightly improved sleep latency (n=4), while doxepin was found to provide a sustained sleep improvement with a safety profile that was comparable to placebo (n=3). Suvorexant showed an improved sleep maintenance with only mild side effects (n=1). One study detected increased adverse effects of trazodone after three months, but did not evaluate the effect on sleep. Conclusions:The overall level of evidence was limited, making it difficult to draw robust conclusions.Preliminary evidence points towards suvorexant, doxepin and possibly ramelteon as effective and safe pharmacological alternatives for treating insomnia in older adults.

Background In the mid-seventies, biliopancreatic diversion became popular as weight-loss surgery procedure. This bariatric procedure combines distal gastric resection and intestinal malabsorption, leading to greater weight loss and improvement of co-morbidities than other bariatric procedures. Nowadays, biliopancreatic diversion has become obsolete due to the high risk of nutritional complications. However, current patients with biliopancreatic diversions are aging. Consequently, geriatricians and general practitioners will encounter them more often and will be faced with the consequences of late complications. Case presentation A 74-year old female presented with weakness, recurrent falls, confusion, episodes of irresponsiveness, anorexia and weight loss. Her medical history included osteoporosis, herpes encephalitis 8 years prior and a biliopancreatic diversion (Scopinaro surgery) at age 52. Cerebral imaging showed herpes sequelae without major atrophy. Delirium was diagnosed with underlying nutritional deficiencies. Biochemical screening indicated vitamin A deficiency, vitamin E deficiency, zinc deficiency and severe hypoalbuminemia. While thiamin level and fasting blood glucose were normal. However, postprandial hyperinsulinemic hypoglycemia was observed with concomitant signs of confusion and blurred consciousness. After initiating parenteral nutrition with additional micronutrient supplementation, a marked improvement was observed in cognitive and physical functioning. Conclusions Long-term effects of biliopancreatic diversion remain relatively underreported in older patients. However, the anatomical and physiological changes of the gastrointestinal tract can contribute to the development of metabolic and nutritional complications that may culminate in cognitive impairment, functional decline and delirium. Therefore, it is warranted to evaluate the presence of metabolic disturbances and nutritional complications in older patients after biliopancreatic diversion.