Self-management eHealth solutions for menopause - a systematic scoping review.

OBJECTIVE: The purpose of this scoping review was to highlight the current scientific evidence on eHealth-based information tools for menopause in terms of quality, requirements and previous intervention outcomes. METHODS: We systematically searched electronic databases (Embase, CINAHL, Cochrane Library, Global Health Database [Ovid], Web of Science, ClinicalTrials.gov [NLM], LIVIVO Search Portal [ZB MED] and Google Scholar) from 1974 to March 2022 for relevant records. RESULTS: Our search yielded 1773 records, of which 28 met our inclusion criteria. Thirteen of 28 selected studies were cross-sectional with qualitative content analysis of websites about menopause; 9 studies were cohort studies examining the impact of an eHealth intervention; two studies were randomized controlled trials comparing eHealth tools with conventional ones; and four studies were non-systematic literature reviews. CONCLUSION: This scoping review highlights the potential of eHealth-based information tools for the management of menopause and shows that most eHealth-based information tools are inadequate in terms of readability and the balanced view on information. Providers of eHealth-based information tools should pay attention to a participatory design, readability, balance of content and the use of multimedia tools for information delivery to improve understanding.

Is abeta a sufficient biomarker for monitoring anti-abeta clinical studies? A critical review.

Amyloid-beta (Aß) in Alzheimer's disease (AD) appeared to be a promising target for disease-modifying therapeutic strategies like passive immunotherapy with anti-Aß monoclonal antibodies (mAbs). Biochemical markers in cerebrospinal fluid (CSF) include alterations of Aß that allow the diagnosis of AD. Biomarker strategies, such as the levels of Aß in CSF and plasma, currently play an important role in early clinical trials for AD. Indeed, these strategies have a relevant impact on the outcome of such studies, since the biomarkers are used to monitor the bioactivity of anti-Aß mAbs. The clinical trials of Solanezumab were mainly based on the readout of Aß levels in CSF and plasma, whereas those of Bapineuzumab were based on cognition; however, little is known about the mechanisms altering these biomarker levels, and no biomarker has yet been proven to be a successful predictor for AD therapy. In addition, the Aß biomarkers allow for the determination of free and bound anti-Aß mAb in order to monitor the available amount of bioactive drug and could give hints to the mechanism of action. In this review, we discuss clinical Aß biomarker data and the latest regulatory strategies.

Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets?

Alzheimer's disease (AD) is the most common dementia in the industrialized world, with prevalence rates well over 30% in the over 80-years-old population. The dementia causes enormous costs to the social healthcare systems, as well as personal tragedies for the patients, families and caregivers. AD is strongly associated with Amyloid-beta (Aß) protein aggregation, which results in extracellular plaques in the brain, and according to the amyloid cascade hypothesis appeared to be a promising target for the development of AD therapeutics. Within the past decade convincing data has arisen positioning the soluble prefibrillar Aß-aggregates as the prime toxic agents in AD. However, different Aß aggregate species are described but their remarkable metastability hampers the identification of a target species for immunization. Passive immunotherapy with monoclonal antibodies (mAbs) against Aß is in late clinical development but recently the two most advanced mAbs, Bapineuzumab and Solanezumab, targeting an N-terminal or central epitope, respectively, failed to meet their target of improving or stabilizing cognition and function. Preliminary data from off-label treatment of a small cohort for 3 years with intravenous polyclonal immunoglobulins (IVIG) that appear to target different conformational epitopes indicate a cognitive stabilization. Thus, it might be the more promising strategy reducing the whole spectrum of Aß-aggregates than to focus on a single aggregate species for immunization.

Restoring long-term potentiation impaired by amyloid-beta oligomers: comparison of an acetylcholinesterase inhibitior and selective neuronal nicotinic receptor agonists.

As nicotinic acetylcholine receptor (nAChR) agonists directly address cholinergic neurotransmission with potential impact on glutamatergic function, they are considered as potential new symptomatic treatment options for Alzheimer's disease compared to the indirectly operating acetylcholinesterase inhibitors such as the current gold standard donepezil. In order to evaluate the therapeutic value of nAChR activation to ameliorate cognitive dysfunction, a direct comparison between α4ß2, α7 nAChR agonists, and donepezil was performed on the level of an ex vivo experimental model of impaired memory formation. First, we demonstrated that amyloid beta (Aß)42 oligomers, which are believed to be the synaptotoxic Aß-species causally involved in the pathophysiology of Alzheimer's disease, have a detrimental effect on long-term potentiation (LTP) in the CA1 region of rat hippocampal slices, a widely used cellular model of learning and memory. Second, we investigated the potential of donepezil, the α4ß2 nAChR agonist TC-1827 and the α7 nAChR partial agonist SSR180711 to reverse Aß42 oligomer induced LTP impairment. Donepezil showed only a slight reversal of Aß42 oligomer induced impairment of early LTP, and had no effect on Aß42 oligomer induced impairment of late LTP. The same was demonstrated for the α4ß2 nAChR agonist TC-1827. In contrast, the α7 nAChR partial agonist SSR180711 completely rescued early as well as late LTP impaired by Aß42 oligomers. As activating α7 nAChRs was found to be most efficacious in restoring Aß42 oligomer induced LTP deficits, targeting α7 nAChRs might represent a powerful alternative approach for symptomatic treatment of AD.

Globular and protofibrillar aß aggregates impair neurotransmission by different mechanisms.

In Alzheimer's disease, substantial evidence indicates the causative role of soluble amyloid ß (Aß) aggregates. Although a variety of Aß assemblies have been described, the debate about their individual relevance is still ongoing. One critical issue hampering this debate is the use of different methods for the characterization of endogenous and synthetic peptide and their intrinsic limitations for distinguishing Aß aggregates. Here, we used different protocols for the establishment of prefibrillar Aß assemblies with varying morphologies and sizes and compared them in a head-to-head fashion. Aggregation was characterized via the monomeric peptide over time until spheroidal, protofibrillar, or fibrillar Aß aggregates were predominant. It could be shown that a change in the ionic environment induced a structural rearrangement, which consequently confounds the delineation of a measured neurotoxicity toward a distinct Aß assembly. Here, neuronal binding and hippocampal neurotransmission were found to be suitable to account for the synaptotoxicity to different Aß assemblies, based on the stability of the applied Aß aggregates in these settings. In contrast to monomeric or fibrillar Aß, different prefibrillar Aß aggregates targeted neurons and impaired hippocampal neurotransmission with nanomolar potency, albeit by different modalities. Spheroidal Aß aggregates inhibited NMDAR-dependent long-term potentiation, as opposed to protofibrillar Aß aggregates, which inhibited AMPAR-dominated basal neurotransmission. In addition, a provoked structural conversion of spheroidal to protofibrillar Aß assemblies resulted in a time-dependent suppression of basal neurotransmission, indicative of a mechanistic switch in synaptic impairment. Thus, we emphasize the importance of addressing the metastability of prefacto characterized Aß aggregates in assigning a biological effect.