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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.

Objective The Western Australia Olfactory Memory Test (WAOMT) is a newly developed test designed to meet a need for a comprehensive measure of olfactory episodic memory (OEM) for clinical and research applications. Method This study aimed to establish the psychometric properties of the WAOMT in a sample of 209 community-dwelling older adults. An independent sample of 27 test-naïve participants were recruited to assess test retest reliability (between 7 and 28 days). Scale psychometric properties were examined using item response theory methods, combined samples (final N = 241). Convergent validity was assessed by comparing performance on the WAOMT with a comprehensive neuropsychological battery of domains (verbal and visual episodic memory, and odor identification), as well as other neuropsychological skills. Based on previous literature, it was predicted that the WAOMT would be positively correlated with conceptually similar cognitive domains. Results The WAOMT is a psychometrically sound test with adequate reliability properties and demonstrated convergent validity with tests of verbal and episodic memory and smell identification. Patterns of performance highlight learning and memory characteristics unique to OEM (e.g., learning curves, cued and free recall). Conclusion Clinical and research implications include streamlining future versions of the WAOMT to ease patient and administrative burden, and the potential to reliably detect early neuropathological changes in healthy older adults with nonimpaired OEM abilities.

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.

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer’s disease dementia (AD)) as an ‘Inception cohort’ who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an ‘Enrichment cohort’ (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

Background: Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable. Objective: Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years. Methods: Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed by a discovery phase analyses of additional regions. SCPs were aged 70 + at baseline, scoring at/above normative memory (CVLT-II) levels for demographically similar individuals aged 30–44 years old, and in the unimpaired range for all other cognitive domains over the course of the study. Results: In linear mixed models, following adjustment for multiple comparisons, there were no significant differences between rates of thinning or volume atrophy between SCPs and TOAs in previously identified ROIs, or the discovery phase analyses. With only amyloid-β negative individuals in the analyses, again there were no significant differences between SCPs and TOAs. Conclusion: The increased methodological rigor in classifying groups, together with the influence of cognitive reserve, are discussed as potential factors accounting for our findings as compared to the extant literature on those with superior cognitive performance for their age.

Background CSF biomarkers are well-established for routine clinical use, yet a paucity of comparative assessment exists regarding CSF extraction methods during lumbar puncture. Here, we compare in detail biomarker profiles in CSF extracted using either gravity drip or aspiration. Methods Biomarkers for β-amyloidopathy (Aβ1–42, Aβ1–40), tauopathy (total tau), or synapse pathology (BACE1, Neurogranin Trunc-p75, α-synuclein) were assessed between gravity or aspiration extraction methods in a sub-population of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study (cognitively normal, N = 36; mild cognitive impairment, N = 8; Alzheimer’s disease, N = 6). Results High biomarker concordance between extraction methods was seen (concordance correlation > 0.85). Passing Bablock regression defined low beta coefficients indicating high scalability. Conclusions Levels of these commonly assessed CSF biomarkers are not influenced by extraction method. Results of this study should be incorporated into new consensus guidelines for CSF collection, storage, and analysis of biomarkers.

Objectives: The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia. Methods: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years. Results: Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status. Conclusions: Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.

Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3–4 years later (NC = 8; MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aβ1-40: p = 0.001; Aβ1-42: p = 0.0004) and T2 (Aβ1-40: p = 0.001; Aβ1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma Aβ1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger sample sets are required.

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer’s disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ɛ4 and rs11023139 in individuals with high amyloid-β burden. APOE ɛ4/rs11023139-A carriers declined significantly faster than APOE ɛ4/rs11023139-G_G carriers in measures of global cognition (p = 0.011) and verbal episodic memory (p = 0.020). Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ɛ4 cognitively normal older adults with a high neocortical amyloid-β burden.

Background:Cerebral amyloid angiopathy (CAA) is one of the major causes of intracerebral hemorrhage and vascular dementia in older adults. Early diagnosis will provide clinicians with an opportunity to intervene early with suitable strategies, highlighting the importance of pre-symptomatic CAA biomarkers. Objective:Investigation of pre-symptomatic CAA related blood metabolite alterations in Dutch-type hereditary CAA mutation carriers (D-CAA MCs). Methods:Plasma metabolites were measured using mass-spectrometry (AbsoluteIDQ® p400 HR kit) and were compared between pre-symptomatic D-CAA MCs (n = 9) and non-carriers (D-CAA NCs, n = 8) from the same pedigree. Metabolites that survived correction for multiple comparisons were further compared between D-CAA MCs and additional control groups (cognitively unimpaired adults). Results:275 metabolites were measured in the plasma, 22 of which were observed to be significantly lower in theD-CAAMCs compared to D-CAA NCs, following adjustment for potential confounding factors age, sex, and APOE ε4 (p < 0.05). After adjusting for multiple comparisons, only spermidine remained significantly lower in theD-CAAMCscompared to theD-CAA NCs (p < 0.00018). Plasma spermidine was also significantly lower in D-CAA MCs compared to the cognitively unimpaired young adult and older adult groups (p < 0.01). Spermidinewas also observed to correlate with CSF Aβ40 (rs = 0.621, p = 0.024), CSF Aβ42 (rs = 0.714, p = 0.006), and brain Aβ load (rs = –0.527, p = 0.030). Conclusion:The current study provides pilot data on D-CAA linked metabolite signals, that also associated with Aβ neuropathology and are involved in several biological pathways that have previously been linked to neurodegeneration and dementia.

Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1–42/Aβ1–40 ratio, a blood-based marker associated with brain Aβ load, in participants (65–90 years) categorised into low (Aβ−, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1–42, and Aβ1–40 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher (p < 0.00001), and plasma Aβ1–42/Aβ1–40 ratios were significantly lower (p < 0.005), in Aβ+ participants compared to Aβ− participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished Aβ+ from Aβ− (area under the curve, AUC = 0.78), but was outperformed when plasma GFAP was added to the base model (AUC = 0.91) and further improved with plasma Aβ1–42/Aβ1–40 ratio (AUC = 0.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1–42/Aβ1–40 ratios) for cognitively normal older adults at risk of AD.

Objective: Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults. Methods: Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention. Results: The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (β = 0.29, p = 0.036, r = 0.27), right supplementary motor area (β = 0.30, p = 0.031, r = 0.29), and both right (β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups. Conclusions: At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.

Introduction This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD). Methods Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ−) or presence (Aβ+) of brain amyloidosis. Results Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ− CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ− CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ− CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume. Discussion These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.

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.

Age-related decrease in testosterone levels is a potential risk factor for cognitive decline in older men. However, observational studies and clinical trials have reported inconsistent results on the effects of testosterone on individual cognitive domains. Null findings may be attributed to factors that studies have yet to consider. In particular, individual variations in polyglutamine (CAG) length in the androgen receptor (AR) gene could alter androgenic activity in brain regions associated with cognitive processes including memory and executive functions. However, the role of AR CAG repeat length as a moderator of the relationship between testosterone levels and cognition has not been investigated. Therefore, we aimed to examine the relationship between baseline calculated free testosterone (cFT) levels, change in cFT levels over 18 months and CAG repeat length on cognitive performance in memory, executive function, language, attention and processing speed domains. These relationships were examined in 304 cognitively normal older male participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. In the attention and processing speed domain, a short CAG repeat length appears to exacerbate the effects of low baseline cFT levels that are also lower than expected at follow-up. These results highlight that individual variations in AR CAG repeat length should be considered in future studies and clinical trials that examine the complex relationship between testosterone and cognition.

Aim: The present study tested a compensatory executive intervention for prospective memory (goal management training) for the first time in older adults. Prospective memory (the ability to remember and execute a task in the future) declines with age, with significant implications for older adults’ activities of daily living and quality of life. Prospective memory interventions have focused primarily on the retrospective component of prospective memory (e.g., implementation intentions). However, executive dysfunction is also implicated in age-related prospective memory decline. Methods: Community-dwelling older adults were randomly allocated to receive goal management training, implementation intentions or no intervention. Prospective memory was assessed before and after the intervention with a well-validated laboratory-based prospective memory measure. Results: Contrary to predictions, neither goal management training nor implementation intentions were successful at improving prospective memory in healthy older adults. Participants who received goal management training were more likely to have difficulty comprehending the intervention. Post-hoc analyses suggested implementation intentions improved prospective memory specifically for participants with poorer baseline prospective memory. Conclusions: These results represent important cautionary findings about the possible limitations of goal management training to improve prospective memory in older adults. Future research should also consider the role of baseline prospective memory ability in affecting response to compensatory intervention.

Background Physical inactivity has been consistently linked to increased risk of cognitive decline; however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements; however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition. Methods This multi-arm pilot randomised clinical trial investigated the effects of 6 months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12 months post-intervention. Ninety-nine cognitively normal men and women (aged 60–80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e. high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test. Results There was a dose-dependent effect of exercise intensity on cardiorespiratory fitness, whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition. Conclusions We did not observe a direct effect of exercise on cognition. Future work in this field should be appropriately designed and powered to examine factors that may contribute to individual variability in response to intervention.

Background: Objectively measuring auditory functions has been proposed as an avenue in differentiating normal age-related cognitive dysfunction from Alzheimer’s disease (AD) and its prodromal states. Previous research has suggested auditory event-related potentials (AERPs) to be non-invasive, cost-effective, and efficient biomarkers for the diagnosis of AD. Objective: The objective of this paper is to review the published literature on AERPs measures in older adults diagnosed with AD and those at higher risk of developing AD, i.e., mild cognitive impairment (MCI) and subjective cognitive decline. Methods: The search was performed on six major electronic databases (Ovid MEDLINE, OVID EMBASE, PsycINFO, PubMed, Scopus, and CINAHL Plus). Articles identified prior to 7 May 2019 were considered for this review. A random effects meta-analysis and analysis of between study heterogeneity was conducted using the Comprehensive Meta-Analysis software. Results: The search identified 1,076 articles; 74 articles met the full inclusion criteria and were included in the systematic review, and 47 articles were included into the analyses. Pooled analysis suggests that AD participants can be differentiated from controls due to significant delays in ABR, N100, P200, N200, and P300 latencies. P300 amplitude was significantly smaller in AD participants compared to controls. P300 latencies differed significantly between MCI participants and controls based on the pooled analysis. Conclusion: The findings of this review indicate that some AERPs may be valuable biomarkers of AD. In conjunction with currently available clinical and neuropsychological assessments, AERPs can aid in screening and diagnosis of prodromal AD.

Background: The link between cholesterol and Alzheimer’s disease (AD) has received much attention, as evidence suggests high levels of cholesterol might be an AD risk factor. The carriage of cholesterol and lipids through the body is mediated via lipoproteins, some of which, particularly apolipoprotein E (ApoE), are intimately linked with AD. In humans, high density lipoprotein (HDL) is regarded as a “good” lipid complex due to its ability to enable clearance of excess cholesterol via ‘cholesterol reverse transport’, although its activities in the pathogenesis of AD are poorly understood. There are several subclasses of HDL; these range from the newly formed small HDL, to much larger HDL. Objective: We examined the major subclasses of HDL in healthy controls, mild cognitively impaired, and AD patients who were not taking statins to determine whether there were HDL profile differences between the groups, and whether HDL subclass levels correlated with plasma amyloid-β (Aβ) levels or brain Aβ deposition. Methods: Samples from AIBL cohort were used in this study. HDL subclass levels were assessed by Lipoprint while Aβ1–42 levels were assessed by ELISA. Brain Aβ deposition was assessed by PET scan. Statistical analysis was performed using parametric and non-parametric tests. Results: We found that small HDL subclass is reduced in AD patients and it correlates with cognitive performance while plasma Aβ concentrations do not correlate with lipid profile or HDL subfraction levels. Conclusion: Our data indicate that AD patients exhibit altered plasma HDL profile and that HDL subclasses correlate with cognitive performances.

Background There is a paucity of interventional research that systematically assesses the role of exercise intensity and cardiorespiratory fitness, and their relationship with executive function in older adults. To address this limitation, we have examined the effect of a systematically manipulated exercise intervention on executive function. Methods Ninety-nine cognitively normal participants (age = 69.10 ± 5.2 years; n = 54 female) were randomized into either a high-intensity cycle-based exercise, moderate-intensity cycle-based exercise, or no-intervention control group. All participants underwent neuropsychological testing and fitness assessment at baseline (preintervention), 6-month follow-up (postintervention), and 12-month postintervention. Executive function was measured comprehensively, including measures of each subdomain: Shifting, Updating/ Working Memory, Inhibition, Verbal Generativity, and Nonverbal Reasoning. Cardiorespiratory fitness was measured by analysis of peak aerobic capacity; VO2peak. Results First, the exercise intervention was found to increase cardiorespiratory fitness (VO2peak) in the intervention groups, in comparison to the control group (F =10.40, p≤0.01). However, the authors failed to find mean differences in executive function scores between the high-intensity, moderate intensity, or inactive control group. On the basis of change scores, cardiorespiratory fitness was found to associate positively with the executive function (EF) subdomains of Updating/Working Memory (β = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (β = 0.30, p = 0.03, r = 0.28) for intervention, but not control participants. Conclusion At the aggregate level, the authors failed to find evidence that 6-months of high-intensity aerobic exercise improves EF in older adults. However, it remains possible that individual differences in experimentally induced changes in cardiorespiratory fitness may be associated with changes in Updating/ Working Memory and Verbal Ge

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF‐L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF‐L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass‐spectrometry (AbsoluteIDQ® p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine; ADMA, kynurenine, trans‐4‐hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF‐L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid‐β load (Aβ ±) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF‐L in both Aβ‐ and Aβ+ groups, ADMA, proline, arginine, asparagine, phenylalanine and acylcarnitine species correlated with NF‐L only in the Aβ+ group after adjusting for confounding variables, suggesting that the association of these metabolites with neurodegeneration may be relevant to AD‐related neuropathology. Metabolites identified to be associated with plasma NF‐L may have the potential to serve as prognostic markers f

Background/Objective: Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer’s disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-β load (NAL). Methods: Serum hepcidin levels in cognitively normal participants (n = 100) aged between 65–90 years were measured using ELISA. To evaluate NAL, all participants underwent 18F-florbetaben positron emission tomography. A standard uptake value ratio (SUVR)<1.35 was classified as low NAL (n = 65) and ≥1.35 (n = 35) was classified as high NAL. Results: Serum hepcidin was significantly higher in participants with high NAL compared to those with low NAL before and after adjusting for covariates: age, gender, and APOE ɛ4 carriage (p < 0.05). A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve, AUC = 0.766), but was outperformed when serum hepcidin was added to the base model (AUC = 0.794) and further improved with plasma Aβ42/40 ratio (AUC = 0.829). Conclusion: The present findings indicate that serum hepcidin is increased in individuals at risk for AD and contribute to the body of evidence supporting iron dyshomeostasis as an early event of AD. Further, hepcidin may add value to a panel of markers that contribute toward identifying individuals at risk of AD; however, further validation studies are required.

Personality factors have been associated with Alzheimer’s disease (AD) and dementia, but they have not been examined against markers of regional brain glucose metabolism (a primary measure of brain functioning) in older adults without clinically diagnosed cognitive impairment. The relationship between personality factors derived from the five-factor model and cerebral glucose metabolism determined using positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (18F-FDG-PET) was examined in a cohort of 237 non-demented, community-dwelling older adults aged 60–89 years (M ± SD = 73.76 ± 6.73). Higher neuroticism and lower scores on extraversion and conscientiousness were significantly associated with decreased glucose metabolism in brain regions typically affected by AD neuropathological processes, including the hippocampus and entorhinal cortex. Furthermore, while there were significant differences between apolipoprotein E (APOE) ε4 allele carriers and non-carriers on 18F-FDG-PET results in the neocortex and other brain regions (p < 0.05), there was no significant difference between carriers and non-carriers on personality factors and no significant interactions were found between APOE ε4 carriage and personality factors on brain glucose metabolism. In conclusion, we found significant relationships between personality factors and glucose metabolism in neural regions more susceptible to AD neuropathology in older adults without clinically significant cognitive impairment. These findings support the need for longitudinal research into the potential mechanisms underlying the relationship between personality and dementia risk, including measurement of change in other AD biomarkers (amyloid and tau imaging) and how they correspond to change in personality factors. Future research is also warranted to determine whether timely psychological interventions aimed at personality facets (specific aspects or characteristics of personality factors) can affect imagin

Alzheimer’s disease (AD) is the most common form of dementia. Currently, there is no effective medication for the prevention or treatment of AD. This has led to the search for alternative therapeutic strategies. Coconut oil(CO) has a unique fatty acid composition that is rich in medium chain fatty acids(MCFA), a major portion of which directly reaches the liver via the portal vein, thereby bypassing the lymphatic system. Given that brain glucose hypometabolism is a major early hallmark of AD, detectable well before the onset of symptoms, ketone bodies from MCFA metabolism can potentially serve as an alternative energy source to compensate for lack of glucose utilisation in the brain. Additionally, neuroprotective antioxidant properties of CO have been attributed to its polyphenolic content. This review discusses how the metabolism of CO and MCFA may aid in compensating the glucose hypometabolism observed in the AD brain. Furthermore, we present the current evidence of the neuroprotective properties of CO on cognition, amyloid-β pathogenicity, inflammation and oxidative stress. The current review addresses the influence of CO/MCFA on other chronic disorders that are risk factors for AD, and addresses existing gaps in the literature regarding the use of CO/MCFA as a potential treatment for AD.

Background β-amyloid (Aβ) positron emission tomography (PET) imaging is currently the only Food and Drug Administration-approved method to support clinical diagnosis of Alzheimer’s disease (AD). However, numerous research studies support the use of cerebrospinal fluid (CSF) biomarkers, as a cost-efficient, quick and equally valid method to define AD pathology. Methods Using automated Elecsys® assays (Roche Diagnostics) for Aβ (1–42) (Aβ42), Aβ (1–40) (Aβ40), total tau (tTau) and phosphorylated tau (181P) (pTau), we examined CSF samples from 202 participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing cohort, to demonstrate the concordance with pathological AD via PET imaging. Results Ratios Aβ42/Aβ40, tTau/Aβ42 and pTau/Aβ42 had higher receiver operator characteristic—area under the curve (all 0.94), and greater concordance with Aβ-PET (overall percentage agreement ~ 90%), compared with individual biomarkers. Conclusion Strong concordance between CSF biomarkers and Aβ-PET status was observed overall, including for cognitively normal participants, further strengthening the association between these markers of AD neuropathological burden for both developmental research studies and for use in clinical trials.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and neuropathological features, including abnormal deposition of amyloid-β (Aβ) peptides, intracellular neurofibrillary tangles, and neuronal death. Identifying therapeutics which can reduce memory deficits at an early stage of the disease has the advantage of slowing or even reversing disease progression before irreversible brain damage has occurred. Consequently, in this study, we investigated the ability of the histone deacetylase inhibitor sodium butyrate (NaB) to attenuate memory deficits in the 5xFAD mouse model of AD following a 12-week feeding regimen. 5xFAD mice demonstrate a unique time course of Aβ pathology, developing Aβ plaques as early as 2 months. Male mice were assigned to either a control diet or a NaB-supplemented diet which was administered at either 5 mg/kg/day, or 15 mg/kg/day for 12 weeks (each group, N = 15). Supplementation commenced at an early disease stage (8–10 weeks of age). Behavioral testing (contextual and cued fear conditioning) was undertaken, and brain Aβ levels measured, at the end of the 12-week intervention. NaB had profound effects on Aβ levels and on associative learning and cognitive functioning. A 40% reduction in brain Aβ levels and a 25% increase in fear response in both the cued and contextual testing was observed in the NaB-treated animals compared to the control group. These findings suggest that NaB warrants further investigation as a potential therapeutic agent in the treatment of cognitive deficits associated with early stages of AD.

Objective To determine the effect of β-amyloid (Aβ) level on progression risk to mild cognitive impairment (MCI) or dementia and longitudinal cognitive change in cognitively normal (CN) older individuals. Methods All CN from the Australian Imaging Biomarkers and Lifestyle study with Aβ PET and ≥3 years follow-up were included (n = 534; age 72 ± 6 years; 27% Aβ positive; follow-up 5.3 ± 1.7 years). Aβ level was divided using the standardized 0–100 Centiloid scale: <15 CL negative, 15–25 CL uncertain, 26–50 CL moderate, 51–100 CL high, >100 CL very high, noting >25 CL approximates a positive scan. Cox proportional hazards analysis and linear mixed effect models were used to assess risk of progression and cognitive decline. Results Aβ levels in 63% were negative, 10% uncertain, 10% moderate, 14% high, and 3% very high. Fifty-seven (11%) progressed to MCI or dementia. Compared to negative Aβ, the hazard ratio for progression for moderate Aβ was 3.2 (95% confidence interval [CI] 1.3–7.6; p < 0.05), for high was 7.0 (95% CI 3.7–13.3; p < 0.001), and for very high was 11.4 (95% CI 5.1–25.8; p < 0.001). Decline in cognitive composite score was minimal in the moderate group (−0.02 SD/year, p = 0.05), while the high and very high declined substantially (high −0.08 SD/year, p < 0.001; very high −0.35 SD/year, p < 0.001). Conclusion The risk of MCI or dementia over 5 years in older CN is related to Aβ level on PET, 5% if negative vs 25% if positive but ranging from 12% if 26–50 CL to 28% if 51–100 CL and 50% if >100 CL. This information may be useful for dementia risk counseling and aid design of preclinical AD trials.

Emerging evidence indicates that there may be substantial individual variability in exercise-induced cognitive enhancement, which likely contributes to the inconsistent findings regarding exercise and cognition across the literature. Previous research is inconclusive with respect to how genetic risk for Alzheimer’s disease (defined by apolipoprotein, APOE, ε4 allele carriage) modulates the relationship between exercise and cognitive health. PURPOSE: To examine the moderating effect of apolipoprotein E (APOE) ε4 allele carriage on cognition following a six-month exercise intervention. METHODS: Ninety-nine cognitively normal men and women (aged 60-80 years) were randomised to either six-months of high-intensity exercise (n=33), moderate-intensity exercise (n=34) or an inactive control group (n=32). All participants underwent verbal learning and memory assessment using the California Verbal Learning Test (CVLT) at pre- and post-intervention. A series of linear mixed-models were undertaken to examine the effects of a group*time, and group*time*APOE ε4 interaction term on repeated CVLT assessments. RESULTS: No effect of group*time was observed on any of the CVLT sub-scores. However, an effect of group*time*APOE ε4 was observed for CVLT learning (d=0.87, p < 0.01) and CVLT short delay recall (d=0.67, p <0.05). Post-hoc analyses revealed only carriers of the APOE ε4 allele received benefit from the high-intensity intervention, compared with the moderate-intensity and control groups. CONCLUSIONS: No changes in verbal learning and memory were observed from pre- to post-exercise intervention in the whole cohort. However, we observed that APOE ε4 carriers received benefit from the high-intensity exercise intervention in terms of improvement on tasks assessing memory and thinking. Our results indicate that individuals at greater risk of AD, and thus more likely to be experiencing a degree of cognitive decline, may benefit most from exercise.

Background The highly encouraging findings from the Finnish Geriatric Intervention Study (known as FINGER) led to the global initiative for dementia risk reduction known as world-wide FINGERS (WW FINGERS). As part of the collaboration, our Australian AU-ARROW trial will follow the general protocol of the FINGER trial, and will also be aligned with the U.S. arm of the study, US-POINTER, though will have minor cultural and dietary modifications to determine the validity of the intervention in an Australian setting. Method AU-ARROW is a randomised, single-blind 2-year clinical trial that will recruit 600 participants aged 60-79 satisfying specific inclusion/exclusion criteria, including normal cognition and one or more cardiovascular risk factors that place them at greater risk of cognitive decline. Participants will be distributed across two sites (a) Macquarie University Health Clinics, Sydney, NSW and (b) Sarich Neuroscience Research Institute, Edith Cowan University, Perth, WA, and will be randomised equally into either the innovative multi-modal intervention group or the study control group, who will receive general lifestyle advice and annual health check-ups, without treatment. Multi-modal intervention consists of aerobic exercise, resistance training and stretching; dietary advice with monitoring to encourage adherence to the MIND diet; cognitive training sessions via the Brain HQ computerised online training system; and medical monitoring and regular health education sessions. Heart rate trackers, diet and exercise log books, and the monitoring of Brain HQ sessions will all help with adherence. Primary outcome measure is improvement in global cognitive score, measured using neurocognitive tests identical to those in the US-POINTER protocol. Additional neurocognitive tests, physical function improvements, detailed diet monitoring and sleep monitoring will provide added data. The unique extra value of AU-ARROW trial consists of the testing for Alzheimer’s diseas

Objective: Sleep quantity and quality are associated with executive function (EF) in experimental studies, and in individuals with sleep disorders. With advancing age, sleep quantity and quality decline, as does the ability to perform EF tasks, suggesting that sleep disruption may contribute to age-related EF declines. This cross-sectional cohort study tested the hypothesis that poorer sleep quality (i.e., the frequency and duration of awakenings) and/or quantity may partly account for age-related EF deficits. Method: Community-dwelling older adults (N = 184) completed actigraphic sleep monitoring then a range of EF tasks. Two EF factors were extracted using exploratory structural equation modeling. Sleep variables did not mediate the relationship between age and EF factors. Post hoc moderated mediation analyses were conducted to test whether cognitive reserve compensates for sleep-related EF deficits, using years of education as a proxy measure of cognitive reserve. Results: We found a significant interaction between cognitive reserve and the number and frequency of awakenings, explaining a small (approximately 3%), but significant amount of variance in EF. Specifically, in individuals with fewer than 11 years of education, greater sleep disturbance was associated with poorer EF, but sleep did not impact EF in those with more education. There was no association between age and sleep quantity. Conclusions: This study highlights the role of cognitive reserve in the sleep–EF relationship, suggesting individuals with greater cognitive reserve may be able to counter the impact of disturbed sleep on EF. Therefore, improving sleep may confer some protection against EF deficits in vulnerable older adults.

There is currently no effective treatment for Alzheimer’s disease (AD), the most common form of dementia. It has been proposed, however, that a modest delay in onset can significantly reduce the number of cases. Thus, prevention and intervention strategies are currently the focus of much research. In the search for compounds that potentially confer benefit, the Amla fruit and its extracts have drawn attention. Amla preparations have been used for centuries in traditional Indian medicine systems such as Ayurveda, with various parts of the plant used to treat a variety of diseases. Here we review many animal-based studies, and some clinical trials, which have shown that Amla, and its extracts, exert many positive effects on dyslipidemia, hyperglycemia, inflammation, oxidative stress, apoptosis, and autophagy, that contribute to AD risk. Collectively, this evidence suggests that Amla may be of value as part of an effective disease-delaying treatment for AD.

Extensive research supports the use of exercise to protect against Alzheimer’s disease (AD). Nevertheless, there is limited evidence from human studies regarding the mechanisms underlying the positive effects of exercise on the brain. Gene expression determines the extent to which a gene is ‘turned on or off’ and can be used to understand mechanistic pathways. Animal research has demonstrated that exercise influences the expression of genes related to various AD biological pathways; however, the impact of exercise on AD-related gene expression has not yet been studied in humans. PURPOSE: To examine changes in AD-related gene expression following a six-month high-intensity exercise intervention. METHODS: Cognitively normal men and women (60-80y) were randomised to either six-months of work-matched high-intensity exercise (n=33), moderate-intensity exercise (n=34) or an inactive control group (n=32). Blood samples were collected pre- and post-intervention and expression levels from a panel of genes implicated in AD were measured. Analysis of covariance (covaried for age and gender), with adjustment for multiple comparisons, was conducted to determine group differences. RESULTS: Decreases in AD-related gene expression following six months of exercise, compared with the control group. More specifically, gene expression associated with cholesterol metabolism (ABCA1; p < 0.001), amyloid precursor protein processing (ADAM17, BACE1; p < 0.05) and synaptic plasticity (UCHL1; p < 0.001) was favourably altered in the high-intensity exercise intervention, compared with the moderate-intensity intervention and control groups. CONCLUSIONS: Investigation of AD-related gene expression has the potential to play an important role in understanding the biological pathways by which exercise reduces AD risk and contributes to enhanced cognitive health. The current work indicates a dose-dependent effect of exercise intensity on the expression of genes associated with AD, revealing mechanis

The purpose of this investigation was to assess the acute changes in growth factors associated with cognitive health following two ecologically valid, intense resistance exercise sessions. Twenty-nine late-middle-aged adults performed one session of either (a) moderate-load resistance exercise or (b) high-load resistance exercise. Venous blood was collected prior to warm-up, immediately following exercise and 30 min following exercise. Serum was analyzed for brain-derived neurotrophic factor, insulin-like growth factor 1, and vascular endothelial growth factor. Session intensity was determined by blood lactate concentration and session rating of perceived exertion. Postexercise blood lactate was greater following moderate-load when compared with high-load resistance exercise. Subjective session intensity was rated higher by the session rating of perceived exertion following moderate-load when compared with high-load resistance exercise. No differences were observed in serum growth factor levels between groups. Ecologically valid and intense moderate-load or high-load exercise methods do not alter serum growth factor levels in late-middle-aged adults.

Development of tau-based therapies for Alzheimer’s disease requires an understanding of the timing of disease-related changes in tau. We quantified the phosphorylation state at multiple sites of the tau protein in cerebrospinal fluid markers across four decades of disease progression in dominantly inherited Alzheimer’s disease. We identified a pattern of tau staging where site-specific phosphorylation changes occur at different periods of disease progression and follow distinct trajectories over time. These tau phosphorylation state changes are uniquely associated with structural, metabolic, neurodegenerative and clinical markers of disease, and some (p-tau217 and p-tau181) begin with the initial increases in aggregate amyloid-β as early as two decades before the development of aggregated tau pathology. Others (p-tau205 and t-tau) increase with atrophy and hypometabolism closer to symptom onset. These findings provide insights into the pathways linking tau, amyloid-β and neurodegeneration, and may facilitate clinical trials of tau-based treatments.

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 ethi

Purpose: This study examined the central auditory processing (CAP) assessment results of adults between 45 and 85 years of age with probable pre-clinical Alzheimer’s disease – i.e., individuals with subjective memory complaints (SMCs) as compared to those who were not reporting significant levels of memory complaints (non-SMCs). It was hypothesized that the SMC group would perform significantly poorer on tests of central auditory skills compared to participants with non-SMCs (control group). Methods: A total of 95 participants were recruited from the larger Western Australia Memory Study and were classified as SMCs (N = 61; 20 males and 41 females, mean age 71.47 ±7.18 years) and non-SMCs (N = 34; 10 males, 24 females, mean age 68.85 ±7.69 years). All participants completed a peripheral hearing assessment, a CAP assessment battery including Dichotic Digits, Duration Pattern Test, Dichotic Sentence Identification, Synthetic Sentence Identification with Ipsilateral Competing Message (SSI-ICM) and the Quick-Speech-in-Noise, and a cognitive screening assessment. Results: The SMCs group performed significantly poorer than the control group on SSI-ICM −10 and −20 dB signal-to-noise conditions. No significant differences were found between the two groups on the peripheral hearing threshold measurements and other CAP assessments. Conclusions: The results suggest that individuals with SMCs perform poorly on specific CAP assessments in comparison to the controls. The poor CAP in SMC individuals may result in a higher cost to their finite pool of cognitive resources. The CAP results provide yet another biomarker that supports the hypothesis that SMCs may be a primary indication of neuropathological changes in the brain. Longitudinal follow up of individuals with SMCs, and decreased CAP abilities should inform whether this group is at higher risk of developing dementia as compared to non-SMCs and those SMC individuals without CAP difficulties.

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

Some studies have linked bilingualism with a later onset of dementia, Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Not all studies have observed such relationships, however. Differences in study outcomes may be due to methodological limitations and the presence of confounding factors within studies such as immigration status and level of education. We conducted the first systematic review with meta-analysis combining cross-sectional studies to explore if bilingualism might delay symptom onset and diagnosis of dementia, AD, and MCI. Primary outcomes included the age of symptom onset, the age at diagnosis of MCI or dementia, and the risk of developing MCI or dementia. A secondary outcome included the degree of disease severity at dementia diagnosis. There was no difference in the age of MCI diagnosis between monolinguals and bilinguals [mean difference: 3.2; 95% confidence intervals (CI): −3.4, 9.7]. Bilinguals vs. monolinguals reported experiencing AD symptoms 4.7 years (95% CI: 3.3, 6.1) later. Bilinguals vs. monolinguals were diagnosed with dementia 3.3 years (95% CI: 1.7, 4.9) later. Here, 95% prediction intervals showed a large dispersion of effect sizes (−1.9 to 8.5). We investigated this dispersion with a subgroup meta-analysis comparing studies that had recruited participants with dementia to studies that had recruited participants with AD on the age of dementia and AD diagnosis between mono- and bilinguals. Results showed that bilinguals vs. monolinguals were 1.9 years (95% CI: −0.9, 4.7) and 4.2 (95% CI: 2.0, 6.4) older than monolinguals at the time of dementia and AD diagnosis, respectively. The mean difference between the two subgroups was not significant. There was no significant risk reduction (odds ratio: 0.89; 95% CI: 0.68–1.16) in developing dementia among bilinguals vs. monolinguals. Also, there was no significant difference (Hedges’ g = 0.05; 95% CI: −0.13, 0.24) in disease severity at dementia diagnosis between bilinguals and mono

Correction to: Neuropsychology Review https://doi.org/10.1007/s11065-020-09426-8

Poster presentation

The non-synonymous single nucleotide polymorphism (SNP), Val158Met within the Catechol-O-methyltransferase (COMT) gene has been associated with altered levels of cognition and memory performance in cognitively normal adults. This study aimed to investigate the independent and interactional effects of COMT Val158Met on cognitive performance. In particular, it was hypothesised that COMT Val158Met would modify the effect of neocortical Aβ-amyloid (Aβ) accumulation and carriage of the apolipoprotein E (APOE) ε4 allele on cognition in preclinical Alzheimer’s disease (AD). In 598 cognitively normal older adults with known neocortical Aβ levels, linear mixed modelling revealed no significant independent or interactional associations between COMT Val158Met and cognitive decline. These findings do not support previous associations between COMT Val158Met and cognitive performance and suggest this variant does not influence Aβ-amyloid or APOE ε4 driven cognitive decline in a well characterised cohort of cognitively normal older adults.

Background Blood markers indicative of neurodegeneration (neurofilament light chain; NFL), Alzheimer’s disease amyloid pathology (amyloid-β; Aβ), and neuroinflammation (kynurenine pathway; KP metabolites) have been investigated independently in neurodegenerative diseases. However, the association of these markers of neurodegeneration and AD pathology with neuroinflammation has not been investigated previously. Therefore, the current study examined whether NFL and Aβ correlate with KP metabolites in elderly individuals to provide insight on the association between blood indicators of neurodegeneration and neuroinflammation. Methods Correlations between KP metabolites, measured using liquid chromatography and gas chromatography coupled with mass spectrometry, and plasma NFL and Aβ concentrations, measured using single molecule array (Simoa) assays, were investigated in elderly individuals aged 65–90 years, with normal global cognition (Mini-Mental State Examination Score ≥ 26) from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort. Results A positive correlation between NFL and the kynurenine to tryptophan ratio (K/T) reflecting indoleamine 2,3-dioxygenase activity was observed (r = .451, p < .0001). Positive correlations were also observed between NFL and kynurenine (r = .364, p < .0005), kynurenic acid (r = .384, p < .0001), 3-hydroxykynurenine (r = .246, p = .014), anthranilic acid (r = .311, p = .002), and quinolinic acid (r = .296, p = .003). Further, significant associations were observed between plasma Aβ40 and the K/T (r = .375, p < .0005), kynurenine (r = .374, p < .0005), kynurenic acid (r = .352, p < .0005), anthranilic acid (r = .381, p < .0005), and quinolinic acid (r = .352, p < .0005). Significant associations were also observed between plasma Aβ42 and the K/T ratio (r = .215, p = .034), kynurenic acid (r = .214, p = .035), anthranilic acid (r = .278, p = .006), and quinolinic acid (r = .224, p = .027) in the cohort. On stratifying