Impact of aging on the auditory system and related cognitive functions: A narrative review

Age-related hearing loss (ARHL), presbycusis, is a chronic health condition that affects approximately one-third of the world’s population. The peripheral and central hearing alterations associated with age-related hearing loss have a profound impact on perception of verbal and non-verbal auditory stimuli. The high prevalence of hearing loss in the older adults corresponds to the increased frequency of dementia in this population. Therefore, researchers have focused their attention on age-related central effects that occur independent of the peripheral hearing loss as well as central effects of peripheral hearing loss and its association with cognitive decline and dementia. Here we review the current evidence for the age-related changes of the peripheral and central auditory system and the relationship between hearing loss and pathological cognitive decline and dementia. Furthermore, there is a paucity of evidence on the relationship between ARHL and established biomarkers of Alzheimer’s disease, as the most common cause of dementia. Such studies are critical to be able to consider any causal relationship between dementia and ARHL. While this narrative review will examine the pathophysiological alterations in both the peripheral and central auditory system and its clinical implications, the question remains unanswered whether hearing loss causes cognitive impairment or vice versa

Multiplex biomarkers in blood

Advances in the field of blood biomarker discovery will help in identifying Alzheimer\u27s disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discusses some recent past and current approaches being taken by researchers in the field. Individual blood biomarkers have been unsuccessful in defining the disease pathology, progression and thus diagnosis. This directs to the need for discovering a multiplex panel of blood biomarkers as a promising approach with high sensitivity and specificity for early diagnosis. However, it is a great challenge to standardize a worldwide blood biomarker panel due to the innate differences in the population tested, nature of the samples and methods utilised in different studies across the globe. We highlight several issues that result in the lack of reproducibility in this field of research currently faced by researchers. Several important measures are summarized towards the end of the review that can be taken to minimize the variability among various centres

Dietary Patterns Associated with Alzheimer\u27s 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

Auditory electrophysiological assessments of Alzheimer\u27s disease and preclinical stages: Protocol for a systematic review and meta-analysis

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Introduction Investigating auditory functions in populations at risk of developing Alzheimer\u27s 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 7 th 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. Systematic review registration PROSPERO CRD42019133553

Amla enhances autophagy and modulates beta amyloid metabolism in an in vitro model of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive, fatal neurodegenerative disease characterized by extensive neuronal loss associated with increased accumulation of the beta amyloid (Aβ) protein. Reducing production, preventing aggregation and improving clearance of Aβare areas of active research in the development of therapeutic agents to ameliorate neurodegeneration in AD. The Indian plant amla (Emblicaofficinalis), commonly known as Indian gooseberry, has widely been utilized in traditional Ayurvedic medicine preparations in the treatment of a variety of disease conditions including cardiovascular disease and diabetes: accumulating evidence also suggests that amla may be beneficial in AD. Amla exhibits antioxidant, anti-inflammatory, and anti-apoptotic mechanisms and more recently has been shown to modulate autophagy; a vital protein degradation pathway involved in the clearance of damaged organelles and aggregate proteins in cells. Our own recent in vitro work shows that amla extract enhances autophagy and modulates accumulation of proteolytic products of Amyloid precursor protein (APP) such as APP-C terminal fragments (C99, C83). Amla treatment (50-300 μg/ml) induced a dose-dependent increase in autophagic flux, as measured by Western blotting utilizing an LC3 directed antibody as an autophagosome marker. At similar concentrations, amla treatment also reduced accumulation of APP C-terminal fragment levels by 33 to 77%. However, no significant changes were observed in APP levels, indicating that amla did not alter APP production. Overall, our findings suggest that amla may confer beneficial effects through modulating autophagy and Aβ metabolism, and warrants further investigation as a potential therapeutic agent in ADhttps://ro.ecu.edu.au/ecuposters/1026/thumbnail.jp

Association of plasma neurofilament light chain with glycaemic control and insulin resistance in middle-aged adults

Aims: This study aimed to determine the association of plasma neurofilament light (NfL), a marker of neurodegeneration, with diabetes status and glycaemic parameters in people with normal glycaemia (NG), pre-diabetes (PD) and type 2 diabetes (T2D). Methods: Clinical and descriptive data for the diagnostic groups, NG (n=30), PD (n=48) and T2D (n=29), aged between 40 and 75 years were included in this cross-sectional analysis. Plasma NfL levels were analyzed using the ultra-sensitive single-molecule array (Simoa) platform. Results: A positive correlation was evident between plasma NfL and fasting glucose (r = 0.2824; p = 0.0032). Plasma NfL levels were not correlated with fasting insulin and insulin resistance. Plasma Nfl levels were significantly different across the diabetes groups (T2D \u3e PD \u3e NG, p = 0.0046). Post-hoc analysis indicated significantly higher plasma NfL levels in the T2D [12.4 (5.21) pg/mL] group than in the PD [10.2 (4.13) pg/mL] and NG [8.37 (5.65) pg/mL] groups. The relationship between diabetes status and NfL remained significant after adjusting for age, sex, BMI, HOMA-IR and physical activity (adjusted r2 = 0.271, p = 0.035). Conclusions: These results show biomarker evidence of neurodegeneration in adults at risk or with T2D. Larger sample size and longitudinal analysis are required to better understand the application of NfL in people with risk and overt T2D

Understanding the relationship between age-related hearing loss and Alzheimer\u27s 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\u27s 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

Docosahexaenoic acid-rich fish oil supplementation reduces kinase associated with insulin resistance in overweight and obese midlife adults

Targeting kinases linked to insulin resistance (IR) and inflammation may help in reducing the risk of type 2 diabetes (T2D) and Alzheimer’s disease (AD) in its early stages. This study aimed to determine whether DHA-rich fish oil supplementation reduces glycogen synthase kinase (GSK-3), which is linked to both IR and AD. Baseline and post-intervention plasma samples from 58 adults with abdominal obesity (Age: 51.7 ± 1.7 years, BMI: 31.9 ± 0.8 kg/m2) were analysed for outcome measures. Participants were allocated to 2 g DHA-rich fish oil capsules (860 mg DHA + 120 mg EPA) (n = 31) or placebo capsules (n = 27) per day for 12 weeks. Compared to placebo, DHA-rich fish oil significantly reduced GSK-3β by −2.3 ± 0.3 ng/mL. An inverse correlation (p \u3c 0.05) was found between baseline insulin and IR and their changes following intervention only in participants with C-reactive protein levels higher than 2.4 mg/L. DHA-rich fish oil reduces GSK-3 and IR, suggesting a potential role of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) in ameliorating AD risk

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 \u3c .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