Altered expression of Alzheimer's disease-related proteins in male hypogonadal mice

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and beta-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the hippocampus and were not evident in the cerebellum or other brain tissues. Male hpg mice tended to have lower levels of IL-1 beta protein than male littermate controls. Immunohistochemical staining of the basal forebrain revealed that male hpg mice had lower choline acetyltransferase levels per neuron compared with controls. These AD-like changes specific to male hpg mice supports a link between androgen depletion and the development of AD pathology

Impact of bilateral, single‐sided and asymmetrical hearing loss on cognitive functions

Aim of the study was to investigate the impact of single sided, asymmetrical and bilateral sensorineural hearing loss on cognitive and psychological functions of postlingually hearing impaired adults

Comparison of auditory steady-state responses with conventional audiometry in older adults

Behavioral measures, such as pure-tone audiometry (PTA), are commonly used to determine hearing thresholds, however, PTA does not always provide reliable hearing information in difficult to test individuals. Therefore, objective measures of hearing sensitivity that require little-to-no active participation from an individual are needed to facilitate the detection and treatment of hearing loss in difficult to test people. Investigation of the reliability of the auditory steady-state response (ASSR) for measuring hearing thresholds in older adults is limited. This study aimed to investigate if ASSR can be a reliable, objective measure of frequency specific hearing thresholds in older adults. Hearing thresholds were tested at 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz in 50 participants aged between 60 and 85 years old, using automated PTA and ASSR. Hearing thresholds obtained from PTA and ASSR were found to be significantly correlated (p < .001) in a cohort consisting of participants with normal hearing or mild hearing loss. ASSR thresholds were significantly higher as compared to PTA thresholds, but for the majority of cases the difference remained within the clinically acceptable range (15 dB). This study provides some evidence to suggest that ASSR can be a valuable tool for estimating objective frequency-specific hearing thresholds in older adults and indicate that ASSR could be useful in creating hearing treatment plans for older adults who are unable to complete behavioral PTA. Further research on older adults is required to improve the methodological features of ASSR to increase consistency and reliability, as well as minimize some of the limitations associated with this technique

Auditory electrophysiological assessments of Alzheimer’s disease and preclinical stages: Protocol for a systematic review and meta-analysis

Introduction Investigating auditory functions in populations at risk of developing Alzheimer’s disease (AD) using auditory neurophysiological measurements can potentially identify a crucial and sensitive diagnostic window of opportunity in preclinical AD. Auditory electrophysiological assessments have gained interest as possible tools for early diagnosis of AD. This paper outlines the protocol that will be used to systematically review the published literature currently available on auditory electrophysiological assessments that have been used to assess the auditory functions of adults over the age of 60 years diagnosed with AD or its preclinical stages. Methods and analysis All full-length peer-reviewed publications of original data that use auditory electrophysiological assessments in AD and its preclinical stages (subjective cognitive decline (SCD) and mild cognitive impairment (MCI)) will be considered in this review. The search will be performed on major electronic databases (Ovid MEDLINE, Ovid Embase, PsycINFO, PubMed, Scopus and CINAHL Plus) using keywords alone or in combination with Medical Subject Headings divided into two domains; (i) auditory tests and (ii) AD. The database search will be conducted on the 7th of May 2019. Data analysis will be completed and reported in the full review. A random effects meta-analysis will also be conducted using the Comprehensive Meta-Analysis software, V.3. This review will describe which auditory electrophysiological tests have been found to be useful in assessing the auditory function in cognitively impaired adults (MCI and AD) or adults with serious complaints about their cognition (SCD). This review will also identify and describe which auditory electrophysiological test demonstrates the most sensitivity in differentiating people at different stages of cognitive decline. Ethics and dissemination This systematic review focusses on analysing already available literature. Therefore, there will be no requirement for ethical approval. The systematic review findings will be disseminated through peer-reviewed publication as well as relevant media platforms, for example, conferences

Understanding the Relationship Between Age-Related Hearing Loss and Alzheimer’s Disease: A Narrative Review

Evidence suggests that hearing loss (HL), even at mild levels, increases the long-term risk of cognitive decline and incident dementia. Hearing loss is one of the modifiable risk factors for dementia, with approximately 4 million of the 50 million cases of dementia worldwide possibly attributed to untreated HL. This paper describes four possible mechanisms that have been suggested for the relationship between age-related hearing loss (ARHL) and Alzheimer’s disease (AD), which is the most common form of dementia. The first mechanism suggests mitochondrial dysfunction and altered signal pathways due to aging as a possible link between ARHL and AD. The second mechanism proposes that sensory degradation in hearing impaired people could explain the relationship between ARHL and AD. The occupation of cognitive resource (third) mechanism indicates that the association between ARHL and AD is a result of increased cognitive processing that is required to compensate for the degraded sensory input. The fourth mechanism is an expansion of the third mechanism, i.e., the function and structure interaction involves both cognitive resource occupation (neural activity) and AD pathology as the link between ARHL and AD. Exploring the specific mechanisms that provide the link between ARHL and AD has the potential to lead to innovative ideas for the diagnosis, prevention, and/or treatment of AD. This paper also provides insight into the current evidence for the use of hearing treatments as a possible treatment/prevention for AD, and if auditory assessments could provide an avenue for early detection of cognitive impairment associated with AD

Dietary Patterns Associated with Alzheimer?s Disease and Related Chronic Disease Risk: A Review

The world’s population is growing older due to improved healthcare and nutrition. As a result, Alzheimer’s disease (AD) prevalence is rapidly increasing. The focus of the current research climate is shifting from understanding AD pathology and diagnosis to primary prevention and intervention strategies. Diet represents one potential intervention strategy accessible to all. Accumulating evidence suggests diet plays a major role in risk and development of AD and AD-related chronic diseases of the periphery like cardiovascular disease (CVD) and diabetes. This paper reviews studies that have explored the relationship between “a priori” dietary patterns, AD and AD-related chronic disease risk. The dietary patterns we will review are the healthy eating index, healthy diet indicator, recommended food score, and the Mediterranean diet (MeDi). Our review of the literature suggests a generally positive association between healthy diet patterns, AD and AD-related chronic disease risk; however the magnitude of the protective effect is modest in many studies. Consequently, we can only confidently conclude that the MeDi is associated with reduced AD risk, and further studies on the remaining indices need to be carried out. It is our opinion that a combination of dietary scores could predict overall dietary quality and chronic disease risk to a greater extent than one score individually. Analysis in multi-ethnic cohorts, investigating combinations of scores must be completed before firm conclusions can be reached on the ideal combination of scores. Obtaining further insight into the association between dietary patterns, AD and AD-related chronic disease risk may help in prioritizing public health efforts and provide a stronger basis for recommendations to improve dietary patterns

Intake of products containing anthocyanins, flavanols, and flavanones, and cognitive function: A narrative review

The purpose of this review is to examine human research studies published within the past 6 years which evaluate the role of anthocyanin, flavanol, and flavanone consumption in cognitive function, and to discuss potential mechanisms of action underlying any observed benefits. Evidence to date suggests the consumption of flavonoid-rich foods, such as berries and cocoa, may have the potential to limit, or even reverse, age-related declines in cognition. Over the last 6 years, the flavonoid subgroups of anthocyanins, flavanols, and flavanones have been shown to be beneficial in terms of conferring neuroprotection. The mechanisms by which flavonoids positively modulate cognitive function are yet to be fully elucidated. Postulated mechanisms include both direct actions such as receptor activation, neurotrophin release and intracellular signaling pathway modulation, and indirect actions such as enhancement of cerebral blood flow. Further intervention studies conducted in diverse populations with sufficient sample sizes and long durations are required to examine the effect of consumption of flavonoid groups on clinically relevant cognitive outcomes. As populations continue to focus on adopting healthy aging strategies, dietary interventions with flavonoids remains a promising avenue for future research. However, many questions are still to be answered, including identifying appropriate dosage, timeframes for intake, as well as the best form of flavonoids, before definitive conclusions can be drawn about the extent to which their consumption can protect the aging brain

Spontaneous parity violation and minimal Higgs models

In this paper we present a model for the spontaneous breaking of parity with two Higgs doublets and two neutral Higgs singlets which are even and odd under D-parity. The condition $v_R >>v_L$ can be satisfied without introducing bidoublets and it is induced by the breaking of D-parity through the vacuum expectation value of the odd Higgs singlet. Examples of left-right symmetric and mirror fermions models in grand unified theories are presented.Comment: Revised version. Accepted in Eur. Phys. Journal

Systematic review protocol for assessing central auditory functions of Alzheimer’s disease and its preclinical stages

Introduction: A number of studies have reported an association between peripheral hearing impairment, central auditory processing and Alzheimer’s disease (AD) and its preclinical stages. Both peripheral hearing impairment and central auditory processing disorders are observed many years prior to the clinical manifestation of AD symptoms, hence, providing a long window of opportunity to investigate potential interventions against neurodegenerative processes. This paper outlines the protocol for a systematic review of studies examining the central auditory processing functions in AD and its preclinical stages, investigated through behavioural (clinical assessments that require active participation) central auditory processing tests. Methods and analysis: We will use the keywords and Medical Subject Heading terms to search the following electronic databases: MEDLINE, PsychINFO, PubMed, Scopus, EMBASE and CINAHL Plus. Studies including assessments of central auditory function in adults diagnosed with dementia, AD and its preclinical stages that were published before 8 May 2019 will be reviewed. This review protocol will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Data analysis and search results will be reported in the full review. This manuscript has designed the protocols for a systematic review that will identify the behavioural clinical central auditory processing measures that are sensitive to the changes in auditory function in adults with AD and its preclinical stages. Such assessments may subsequently help to design studies to examine the potential impact of hearing and communication rehabilitation of individuals at risk of AD. Ethics and dissemination: Ethical approval is not required as this manuscript only reports the protocols for conducting a systematic review as primary data will only be reviewed and not be collected. The results of this systematic review will be disseminated through publication and in scientific conferences

Medium-chain triglyceride supplementation may increase working memory in older adults: A pilot study

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