Clearance and transport of amyloid ß by peripheral monocytes correlate with Alzheimer's disease progression.

Impaired clearance of amyloid ß (Aß) in late-onset Alzheimer's disease (AD) affects disease progression. The role of peripheral monocytes in Aß clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aß-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes in human cerebrospinal fluid (CSF) and their migration in an APP/PS1 mouse model. The assay reveals macrophage-like Aß-binding monocytes with high phagocytic potential in both the periphery and CNS. We find lower surface Aß levels in mild cognitive impairment (MCI) and AD-dementia patients compared to cognitively unimpaired individuals. Monocyte infiltration from blood to CSF and migration from CNS to peripheral lymph nodes and blood are observed. Here we show that Aß-binding monocytes may play a role in CNS Aß clearance, suggesting their potential as a biomarker for AD diagnosis and monitoring.

15 Years of Longitudinal Genetic, Clinical, Cognitive, Imaging, and Biochemical Measures in DIAN.

This manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimer's disease (AD). DIAN Obs is an international collaborative longitudinal study initiated in 2008 with support from the National Institute on Aging (NIA), designed to obtain comprehensive and uniform data on brain biology and function in individuals at risk for autosomal dominant AD (ADAD). ADAD gene mutations in the amyloid protein precursor (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) genes are deterministic causes of ADAD, with virtually full penetrance, and a predictable age at symptomatic onset. Data and specimens collected are derived from full clinical assessments, including neurologic and physical examinations, extensive cognitive batteries, structural and functional neuro-imaging, amyloid and tau pathological measures using positron emission tomography (PET), flurordeoxyglucose (FDG) PET, cerebrospinal fluid and blood collection (plasma, serum, and whole blood), extensive genetic and multi-omic analyses, and brain donation upon death. This comprehensive evaluation of the human nervous system is performed longitudinally in both mutation carriers and family non-carriers, providing one of the deepest and broadest evaluations of the human brain across decades and through AD progression. These extensive data sets and samples are available for researchers to address scientific questions on the human brain, aging, and AD.

The Crosstalk Between Amyloid-ß, Retina, and Sleep for the Early Diagnosis of Alzheimer's Disease: A Narrative Review.

Alzheimer's disease (AD) is the most common type of dementia, which is characterised by progressive memory loss and accumulation of hallmark markers amyloid-ß (Aß) and neurofibrillary tangles in the diseased brain. The current gold standard diagnostic methods have limitations of being invasive, costly, and not easily accessible. Thus, there is a need for new avenues, such as imaging the retina for early AD diagnosis. Sleep disruption is symptomatically frequent across preclinical and AD subjects. As circadian activity, such as the sleep-wake cycle, is linked to the retina, analysis of their association may be useful additions for achieving predictive AD diagnosis. In this narrative review, we provide an overview of human retina studies concerning the deposition of Aß, the role of the retina in sleep-wake cycle, the disruption of sleep in AD, and to gather evidence for the associations between Aß, the retina, and sleep. Understanding the mechanisms behind the associations between Aß, retina, and sleep could assist in the interpretation of retinal changes accurately in AD.

Hyperspectral Retinal Imaging as a Non-Invasive Marker to Determine Brain Amyloid Status.

Background: As an extension of the central nervous system (CNS), the retina shares many similarities with the brain and can manifest signs of various neurological diseases, including Alzheimer's disease (AD). Objective: To investigate the retinal spectral features and develop a classification model to differentiate individuals with different brain amyloid levels. Methods: Sixty-six participants with varying brain amyloid-ß protein levels were non-invasively imaged using a hyperspectral retinal camera in the wavelength range of 450-900 nm in 5 nm steps. Multiple retina features from the central and superior views were selected and analyzed to identify their variability among individuals with different brain amyloid loads. Results: The retinal reflectance spectra in the 450-585 nm wavelengths exhibited a significant difference in individuals with increasing brain amyloid. The retinal features in the superior view showed higher inter-subject variability. A classification model was trained to differentiate individuals with varying amyloid levels using the spectra of extracted retinal features. The performance of the spectral classification model was dependent upon retinal features and showed 0.758-0.879 accuracy, 0.718-0.909 sensitivity, 0.764-0.912 specificity, and 0.745-0.891 area under curve for the right eye. Conclusions: This study highlights the spectral variation of retinal features associated with brain amyloid loads. It also demonstrates the feasibility of the retinal hyperspectral imaging technique as a potential method to identify individuals in the preclinical phase of AD as an inexpensive alternative to brain imaging.

The Relationship between Diet, Depression, and Alzheimer's Disease: A Narrative Review.

PURPOSE OF REVIEW: This narrative review evaluates the role of diet in the relationship between depression and Alzheimer's disease (AD). RECENT FINDINGS: AD and depression are often comorbid, and depression appears to independently increase the future risk of AD. Evidence suggests diet influences the risk of both conditions directly and indirectly. Diet impacts neurochemical and biological processes that may affect the development and progression of depression and cognitive dysfunction. The dietary components offering the greatest protection against depression and AD are yet to be determined. Current evidence highlights the importance of polyphenolic compounds, folate, B vitamins, and polyunsaturated fatty acids, along with adherence to dietary patterns like the Mediterranean diet, which includes multiple beneficial dietary factors. SUMMARY: The investigation of dietary factors in the prevention of depression and AD is a comparatively young field of research. Comprehensive highly characterised longitudinal datasets and advanced analytical approaches are required to further examine the complex relationship between diet, depression, and AD. There is a critical need for more research in this area to develop effective preventive strategies aimed at maintaining mental and physical health with advancing age.

The McCusker Subjective Cognitive Impairment Inventory (McSCI): a novel measure of perceived cognitive decline.

BACKGROUND: Subjective cognitive decline (SCD), i.e. self/other-reported concerns on one's cognitive functioning without objective evidence of significant decline, is an indicator of dementia risk. There is little consensus on reliability and validity of the available SCD measures. Therefore, introducing a novel and psychometrically sound measure of SCD is timely. OBJECTIVE: The psychometric properties of a new SCD measure, the McCusker Subjective Cognitive Impairment Inventory-Self-Report (McSCI-S), are reported. METHODS: Through review of previously published measures as well as our clinical and research data on people with SCD, we developed a 46-item self-report questionnaire to assess concerns on six cognitive domains, namely, memory, language, orientation, attention and concentration, visuoconstruction abilities and executive function. The McSCI-S was examined in a cohort of 526 participants using factor analysis, item response theory analysis and receiver operating characteristic (ROC) curve. RESULTS: A unidimensional model provided acceptable fit (CFI = 0.94, TLI = 0.94, RMSEA [90% CI] = 0.052 [.049, 0.055], WRMR = 1.45). The McSCI-S internal consistency was excellent (.96). A cut-off score of ≥24 is proposed to identify participants with SCDs. Higher McSCI-S scores were associated with poorer general cognition, episodic verbal memory, executive function and greater memory complaints and depressive scores (P < .001), controlling for age, sex and education. CONCLUSIONS: Excellent reliability and construct validity suggest the McSCI-S estimates SCDs with acceptable accuracy while capturing self-reported concerns for various cognitive domains. The psychometric analysis indicated that this measure can be used in cohort studies as well as on individual, clinical settings to assess SCDs.

Evolution of white matter hyperintensity segmentation methods and implementation over the past two decades; an incomplete shift towards deep learning.

This systematic review examines the prevalence, underlying mechanisms, cohort characteristics, evaluation criteria, and cohort types in white matter hyperintensity (WMH) pipeline and implementation literature spanning the last two decades. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we categorized WMH segmentation tools based on their methodologies from January 1, 2000, to November 18, 2022. Inclusion criteria involved articles using openly available techniques with detailed descriptions, focusing on WMH as a primary outcome. Our analysis identified 1007 visual rating scales, 118 pipeline development articles, and 509 implementation articles. These studies predominantly explored aging, dementia, psychiatric disorders, and small vessel disease, with aging and dementia being the most prevalent cohorts. Deep learning emerged as the most frequently developed segmentation technique, indicative of a heightened scrutiny in new technique development over the past two decades. We illustrate observed patterns and discrepancies between published and implemented WMH techniques. Despite increasingly sophisticated quantitative segmentation options, visual rating scales persist, with the SPM technique being the most utilized among quantitative methods and potentially serving as a reference standard for newer techniques. Our findings highlight the need for future standards in WMH segmentation, and we provide recommendations based on these observations.

Association of Basal Forebrain Atrophy With Cognitive Decline in Early Alzheimer Disease.

BACKGROUND AND OBJECTIVES: In early Alzheimer disease (AD), ß-amyloid (Aß) deposition is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aß-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationship between BF atrophy and the decline in memory and attention in patients with early AD. METHODS: Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who completed Aß-PET imaging and repeated MRI and cognitive assessments were included. At baseline, participants were classified based on their clinical dementia stage and Aß status, yielding groups that were cognitively unimpaired (CU) Aß-, CU Aß+, and mild cognitive impairment (MCI) Aß+. Linear mixed-effects models were used to assess changes in volumetric measures of BF subregions and the hippocampus and changes in AIBL memory and attention composite scores for each group compared with CU Aß- participants. Associations between Aß burden, brain atrophy, and cognitive decline were evaluated and explored further using mediation analyses. RESULTS: The cohort included 476 participants (72.6 ± 5.9 years, 55.0% female) with longitudinal data from a median follow-up period of 6.1 years. Compared with the CU Aß- group (n = 308), both CU Aß+ (n = 107) and MCI Aß+ (n = 61) adults showed faster decline in BF and hippocampal volumes and in memory and attention (Cohen d = 0.73-1.74). Rates of atrophy in BF subregions and the hippocampus correlated with cognitive decline, and each individually mediated the impact of Aß burden on memory and attention decline. When all mediators were considered simultaneously, hippocampal atrophy primarily influenced the effect of Aß burden on memory decline (ß [SE] = -0.139 [0.032], proportion mediated [PM] = 28.0%) while the atrophy of the posterior nucleus basalis of Meynert in the BF (ß [SE] = -0.068 [0.029], PM = 13.1%) and hippocampus (ß [SE] = -0.121 [0.033], PM = 23.4%) distinctively influenced Aß-related attention decline. DISCUSSION: These findings highlight the significant role of BF atrophy in the complex pathway linking Aß to cognitive impairment in early stages of AD. Volumetric assessment of BF subregions could be essential in elucidating the relationships between the brain structure and behavior in AD.

A cross-cultural study of the Montreal Cognitive Assessment for people with hearing impairment.

BACKGROUND: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long-term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA-H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA-H. METHODS: The current study investigated the performance of the MoCA-H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA-H. RESULTS: In a multiple regression model accounting for age, sex, and education, cultural-linguistic group accounted for 6.89% of variance in the total MoCA-H score. Differences between languages in mean score of up to 2.6 points were observed. CONCLUSIONS: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA-H such that optimal performance cut points for identification of cognitive impairment derived in English-speaking populations are likely inappropriate for use in non-English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA-H.

Sorghum Grain Polyphenolic Extracts Demonstrate Neuroprotective Effects Related to Alzheimer's Disease in Cellular Assays.

Sorghum grain contains high levels and a diverse profile of polyphenols (PPs), which are antioxidants known to reduce oxidative stress when consumed in the diet. Oxidative stress leading to amyloid-ß (Aß) aggregation, neurotoxicity, and mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer's disease (AD). Thus, PPs have gained attention as possible therapeutic agents for combating AD. This study aimed to (a) quantify the phenolic compounds (PP) and antioxidant capacities in extracts from six different varieties of sorghum grain and (b) investigate whether these PP extracts exhibit any protective effects on human neuroblastoma (BE(2)-M17) cells against Aß- and tau-induced toxicity, Aß aggregation, mitochondrial dysfunction, and reactive oxygen species (ROS) induced by Aß and tert-butyl hydroperoxide (TBHP). PP and antioxidant capacity were quantified using chemical assays. Aß- and tau-induced toxicity was determined using the 3-(4,5-dimenthylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTS) assay. The thioflavin T (Th-T) assay assessed anti-Aß aggregation. The dichlorodihydrofluorescein diacetate (DCFDA) assay determined the levels of general ROS and the MitoSOX assay determined the levels of mitochondrial superoxide. Sorghum varieties Shawaya short black-1 and IS1311C possessed the highest levels of total phenolics, total flavonoids, and antioxidant capacity, and sorghum varieties differed significantly in their profile of individual PPs. All extracts significantly increased cell viability compared to the control (minus extract). Variety QL33 (at 2000 µg sorghum flour equivalents/mL) showed the strongest protective effect with a 28% reduction in Aß-toxicity cell death. The extracts of all sorghum varieties significantly reduced Aß aggregation. All extracts except that from variety B923296 demonstrated a significant (p ≤ 0.05) downregulation of Aß-induced and TBHP-induced ROS and mitochondrial superoxide relative to the control (minus extract) in a dose- and variety-dependent manner. We have demonstrated for the first time that sorghum polyphenolic extracts show promising neuroprotective effects against AD, which indicates the potential of sorghum foods to exert a similar beneficial property in the human diet. However, further analysis in other cellular models and in vivo is needed to confirm these effects.

Suboptimal self-reported sleep efficiency and duration are associated with faster accumulation of brain amyloid beta in cognitively unimpaired older adults.

INTRODUCTION: This study investigated whether self-reported sleep quality is associated with brain amyloid beta (Aß) accumulation. METHODS: Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self-reported sleep data, and positron emission tomography-determined brain Aß measured over a minimum of three time points (range 33.3-72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) ε4 allele status, and time, adjusting for sex and baseline age. RESULTS: Sleep duration <6 hours, in APOE ε4 carriers, and sleep efficiency <65%, in the whole sample and APOE ε4 non-carriers, is associated with faster accumulation of brain Aß. DISCUSSION: These findings suggest a role for self-reported suboptimal sleep efficiency and duration in the accumulation of Alzheimer's disease (AD) neuropathology in CU individuals. Additionally, poor sleep efficiency represents a potential route via which individuals at lower genetic risk may progress to preclinical AD. Highlights: In cognitively unimpaired older adults self-report sleep is associated with brain amyloid beta (Aß) accumulation.Across sleep characteristics, this relationship differs by apolipoprotein E (APOE) genotype.Sleep duration <6 hours is associated with faster brain Aß accumulation in APOE ε4 carriers.Sleep efficiency < 65% is associated with faster brain Aß accumulation in APOE ε4 non-carriers.Personalized sleep interventions should be studied for potential to slow Aß accumulation.

The AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU-ARROW): A study protocol for a single-blind, multi-site, randomized controlled trial.

INTRODUCTION: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. METHOD: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55-79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests. DISCUSSION: The finalized AU-ARROW protocol is expected to allow development of an evidence-based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy. Highlights: Study protocol for a single-blind, randomized controlled trial, the AU-ARROW Study.The AU-ARROW Study is a member of the World-Wide FINGERS (WW-FINGERS) initiative.AU-ARROW's primary outcome measure is change in a global composite cognitive score.Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests.Leading to development of an innovative treatment plan to reduce cognitive decline.

The impact of exercise on blood-based biomarkers of Alzheimer's disease in cognitively unimpaired older adults.

Physical activity is a promising preventative strategy for Alzheimer's disease: it is associated with lower dementia risk, better cognition, greater brain volume and lower brain beta-amyloid. Blood-based biomarkers have emerged as a low-cost, non-invasive strategy for detecting preclinical Alzheimer's disease, however, there is limited literature examining the effect of exercise (a structured form of physical activity) on blood-based biomarkers. The current study investigated the influence of a 6-month exercise intervention on levels of plasma beta-amyloid (Aß42, Aß40, Aß42/40), phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) chain in cognitively unimpaired older adults, and as a secondary aim, whether blood-based biomarkers related to cognition. Ninety-nine community-dwelling older adults (69.1 ± 5.2) were allocated to an inactive control, or to moderate or high intensity exercise groups where they cycled twice weekly for six months. At baseline and six months (post-intervention), fasted blood was collected and analysed using single molecule array (SIMOA) assays, and cognition was assessed. Results demonstrated no change in levels of any plasma biomarker from pre- to post-intervention. At baseline, higher NfL was associated with poorer cognition (ß = -0.33, SE = 0.13, adjusted p = .042). Exploratory analyses indicated higher cardiorespiratory fitness was associated with higher NfL and GFAP levels in apolipoprotein E (APOE) ε4 non-carriers compared to ε4 carriers (NfL, ß = -0.43, SE = 0.19, p = .029; GFAP, ß = -0.41, SE = 0.20, p = .044), though this association was mediated by body mass index (BMI). These results highlight the importance of considering BMI in analysis of blood-based biomarkers, especially when investigating differences between APOE ε4 carriers and non-carriers. Our results also indicate that longer follow-up periods may be required to observe exercise-induced change in blood-based biomarkers.

The Role of Diet and Gut Microbiota in Alzheimer's Disease.

Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (Aß) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer's disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of Aß, the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut-brain axis (GBA) in the context of AD progression and pathology have yielded inconsistent findings. This review aims to enhance our understanding of microbial diversity at the species level and the role of these species in AD pathology. Additionally, this review addresses the influence of confounding elements, including diet, probiotics, and prebiotics, on AD throughout different stages (preclinical, mild cognitive impairment (MCI), and AD) of its progression.

Fluid biomarkers in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a type of cerebrovascular disorder characterised by the accumulation of amyloid within the leptomeninges and small/medium-sized cerebral blood vessels. Typically, cerebral haemorrhages are one of the first clinical manifestations of CAA, posing a considerable challenge to the timely diagnosis of CAA as the bleedings only occur during the later disease stages. Fluid biomarkers may change prior to imaging biomarkers, and therefore, they could be the future of CAA diagnosis. Additionally, they can be used as primary outcome markers in prospective clinical trials. Among fluid biomarkers, blood-based biomarkers offer a distinct advantage over cerebrospinal fluid biomarkers as they do not require a procedure as invasive as a lumbar puncture. This article aimed to provide an overview of the present clinical data concerning fluid biomarkers associated with CAA and point out the direction of future studies. Among all the biomarkers discussed, amyloid ß, neurofilament light chain, matrix metalloproteinases, complement 3, uric acid, and lactadherin demonstrated the most promising evidence. However, the field of fluid biomarkers for CAA is an under-researched area, and in most cases, there are only one or two studies on each of the biomarkers mentioned in this review. Additionally, a small sample size is a common limitation of the discussed studies. Hence, it is hard to reach a solid conclusion on the clinical significance of each biomarker at different stages of the disease or in various subpopulations of CAA. In order to overcome this issue, larger longitudinal and multicentered studies are needed.

Physical activity and brain amyloid beta: A longitudinal analysis of cognitively unimpaired older adults.

INTRODUCTION: The current study evaluated the relationship between habitual physical activity (PA) levels and brain amyloid beta (Aß) over 15 years in a cohort of cognitively unimpaired older adults. METHODS: PA and Aß measures were collected over multiple timepoints from 731 cognitively unimpaired older adults participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Aging. Regression modeling examined cross-sectional and longitudinal relationships between PA and brain Aß. Moderation analyses examined apolipoprotein E (APOE) ε4 carriage impact on the PA-Aß relationship. RESULTS: PA was not associated with brain Aß at baseline (ß = -0.001, p = 0.72) or over time (ß = -0.26, p = 0.24). APOE ε4 status did not moderate the PA-Aß relationship over time (ß = 0.12, p = 0.73). Brain Aß levels did not predict PA trajectory (ß = -54.26, p = 0.59). DISCUSSION: Our study did not identify a relationship between habitual PA and brain Aß levels. HIGHLIGHTS: Physical activity levels did not predict brain amyloid beta (Aß) levels over time in cognitively unimpaired older adults (≥60 years of age). Apolipoprotein E (APOE) ε4 carrier status did not moderate the physical activity-brain Aß relationship over time. Physical activity trajectories were not impacted by brain Aß levels.

Predicting neurodegeneration from sleep related biofluid changes.

Sleep-wake disturbances are common in neurodegenerative diseases and may occur years before the clinical diagnosis, potentially either representing an early stage of the disease itself or acting as a pathophysiological driver. Therefore, discovering biomarkers that identify individuals with sleep-wake disturbances who are at risk of developing neurodegenerative diseases will allow early diagnosis and intervention. Given the association between sleep and neurodegeneration, the most frequently analyzed fluid biomarkers in people with sleep-wake disturbances to date include those directly associated with neurodegeneration itself, such as neurofilament light chain, phosphorylated tau, amyloid-beta and alpha-synuclein. Abnormalities in these biomarkers in patients with sleep-wake disturbances are considered as evidence of an underlying neurodegenerative process. Levels of hormonal sleep-related biomarkers such as melatonin, cortisol and orexin are often abnormal in patients with clinical neurodegenerative diseases, but their relationships with the more standard neurodegenerative biomarkers remain unclear. Similarly, it is unclear whether other chronobiological/circadian biomarkers, such as disrupted clock gene expression, are causal factors or a consequence of neurodegeneration. Current data would suggest that a combination of fluid biomarkers may identify sleep-wake disturbances that are most predictive for the risk of developing neurodegenerative disease with more optimal sensitivity and specificity.

REducing Sleep Apnoea for the PrEvention of Dementia (REShAPED): Protocol for a multi-site feasibility randomised controlled trial.

There is accumulating evidence that has linked OSA with increased risk of cognitive decline and dementia. Here we present the protocol for an Australian, multi-site randomised controlled, parallel open-label trial which will evaluate the feasibility for a full-scale trial investigating the effects of treating OSA on cognitive decline in older adults at risk of dementia within memory clinic settings. We will randomise 180 older adults to either the treatment intervention group or control group for 2 years. Inclusion criteria include: 50-85 years; mild-severe OSA (defined average ODI ≥ 10 with 3% oxygen desaturation determined by wrist oximetry over two nights); and subjective cognitive complaints or mild cognitive impairment. The treatment intervention arm aims to achieve an optimal treatment response based on reducing hypoxic burden with either CPAP, mandibular advancement splint, positional therapy, or oxygen therapy. Furthermore, participants will receive up to 8 sessions which involve motivational interviewing, collaborative goal setting, and behavioural sleep management. The control arm will not receive OSA treatment as part of this trial, however there will be no OSA treatment restrictions, and any treatment will be documented. Primary outcomes are 1) acceptability based upon willingness of participants to be randomised; 2) alleviating hypoxic burden by reducing OSA severity; 3) tolerability of the trial burden based upon collection of outcomes over the 2-year follow-up. Secondary outcomes include safety and cognitive function. Outcomes will be collected at 0, 6 and 24-months. This feasibility study aims to will provide the basis for a larger longer-term trial of dementia prevention.

Effect of Virgin Coconut Oil Supplementation on Cognition of Individuals with Mild-to-Moderate Alzheimer's Disease in Sri Lanka (VCO-AD Study): A Randomized Placebo-Controlled Trial.

BACKGROUND: Virgin coconut oil (VCO) is a potential therapeutic approach to improve cognition in Alzheimer's disease (AD) due to its properties as a ketogenic agent and antioxidative characteristics. OBJECTIVE: This study aimed to investigate the effect of VCO on cognition in people with AD and to determine the impact of apolipoprotein E (APOE) ɛ4 genotype on cognitive outcomes. METHODS: Participants of this double-blind placebo-controlled trial (SLCTR/2015/018, 15.09.2015) were 120 Sri Lankan individuals with mild-to-moderate AD (MMSE = 15-25), aged > 65 years, and they were randomly allocated to treatment or control groups. The treatment group was given 30 mL/day of VCO orally and the control group, received similar amount of canola oil, for 24 weeks. The Mini-Mental Sate Examination (MMSE) and Clock drawing test were performed to assess cognition at baseline and at the end of the intervention. Blood samples were collected and analyzed for lipid profile and glycated hemoglobin (HbA1 C) levels.∥Results:There were no significant difference in cognitive scores, lipid profile, and HbA1 C levels between VCO and control groups post-intervention. The MMSE scores, however, improved among APOE ɛ4 carriers who had VCO, compared to non-carriers (2.37, p = 0.021). APOE ɛ4 status did not influence the cognitive scores in the control group. The attrition rate was 30%.∥Conclusion:Overall, VCO did not improve cognition in individuals with mild-to-moderate AD following a 24-week intervention, compared to canola oil. However, it improved the MMSE scores in APOE ɛ4 carriers. Besides, VCO did not compromise lipid profile and HbA1 C levels and is thus safe to consume.

Tackling Dementia Together via The Australian Dementia Network (ADNeT): A Summary of Initiatives, Progress and Plans.

In 2018, the Australian Dementia Network (ADNeT) was established to bring together Australia's leading dementia researchers, people with living experience and clinicians to transform research and clinical care in the field. To address dementia diagnosis, treatment, and care, ADNeT has established three core initiatives: the Clinical Quality Registry (CQR), Memory Clinics, and Screening for Trials. Collectively, the initiatives have developed an integrated clinical and research community, driving practice excellence in this field, leading to novel innovations in diagnostics, clinical care, professional development, quality and harmonization of healthcare, clinical trials, and translation of research into practice. Australia now has a national Registry for Mild Cognitive Impairment and dementia with 55 participating clinical sites, an extensive map of memory clinic services, national Memory and Cognition Clinic Guidelines and specialized screening for trials sites in five states. This paper provides an overview of ADNeT's achievements to date and future directions. With the increase in dementia cases expected over coming decades, and with recent advances in plasma biomarkers and amyloid lowering therapies, the nationally coordinated initiatives and partnerships ADNeT has established are critical for increased national prevention efforts, co-ordinated implementation of emerging treatments for Alzheimer's disease, innovation of early and accurate diagnosis, driving continuous improvements in clinical care and patient outcome and access to post-diagnostic support and clinical trials. For a heterogenous disorder such as dementia, which is now the second leading cause of death in Australia following cardiovascular disease, the case for adequate investment into research and development has grown even more compelling.