Cognitive Brain Research Articles

Exploring the Advantages and Disadvantages of a Whole Foods Approach for Elevating Dietary Nitrate Intake: Have Researchers Concentrated Too Much on Beetroot Juice?

In recent years, a number of studies have explored the potential salutary effects of dietary nitrate, with promising findings emerging. Indeed, numerous investigations have now demonstrated that increasing intake of dietary nitrate can reduce blood pressure, improve endothelial function, decrease platelet aggregation, increase cognitive function and brain perfusion, and enhance exercise performance. Most researchers have explored the health and/or performance effects of dietary nitrate by providing participants with concentrated beetroot juice, which is rich in this compound. Another strategy for increasing/optimising dietary nitrate intake, which could be embraced alongside or instead of nitrate-rich supplements in research and non-research settings, is the consumption of whole nitrate-rich vegetables. In this review, we explore the potential advantages and disadvantages of increasing consumption of various whole nitrate-rich vegetables to augment dietary nitrate intake. We compare the cost, convenience, availability, feasibility/acceptability, and efficacy of consumption of nitrate via whole nitrate-rich vegetables against concentrated beetroot juice ‘shots’ as defined supplements. We also discuss possible strategies that could be used to help individuals maximise their intake of nitrate via whole vegetables, and outline potential avenues for future research.

Abnormal cerebral blood flow and brain function in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) lead to impaired cerebral blood perfusion, which leads to changes in brain function and affects the cognitive function of patients. In this study, cerebral blood flow (CBF) was used to evaluate the effect of T2DM on cerebral perfusion, and functional connectivity (FC) analysis was further used to explore whether the FC between the abnormal CBF region and the whole brain was changed. In addition, amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were used to investigate the changes in spontaneous activity and connectivity strength of the brain network. We recruited 40 T2DM patients and 55 healthy controls (HCs). They underwent 3D-T1WI, rs-fMRI, arterial spin labeling (ASL) sequence scans and a series of cognitive tests. Cognitive test scores and brain imaging indicators were compared between the two groups, and the relationships among laboratory indicators, cognitive test scores, and brain imaging indicators were explored in the T2DM group. Compared to HCs, The CBF values of Calcarine_L and Precuneus_R in the T2DM group were lower. The DC value of Paracentral_Lobule_L and Precuneus_L, and the ALFF value of Hippocampus_L in the T2DM group were higher. In addition, the CBF values of Calcarine_L was negatively correlated with fasting insulin and HOMA_IR. This study found that there were regions of cerebral hypoperfusion in T2DM patients, which are associated with insulin resistance. In addition, we found abnormally elevated brain activity and enhanced functional connectivity in T2DM patients, which we speculated was the compensatory mechanism of brain neural activity.

Markers of limbic system damage following SARS-CoV-2 infection.

Alterations of the limbic system may be present in the chronic phase of SARS-CoV-2 infection. Our aim was to study the long-term impact of this disease on limbic system-related behaviour and its associated brain functional connectivity, according to the severity of respiratory symptoms in the acute phase. To this end, we investigated the multimodal emotion recognition abilities of 105 patients from the Geneva COVID-COG Cohort 223 days on average after SARS-CoV-2 infection (diagnosed between March 2020 and May 2021), dividing them into three groups (severe, moderate or mild) according to respiratory symptom severity in the acute phase. We used multiple regressions and partial least squares correlation analyses to investigate the relationships between emotion recognition, olfaction, cognition, neuropsychiatric symptoms and functional brain networks. Six to 9 months following SARS-CoV-2 infection, moderate patients exhibited poorer recognition abilities than mild patients for expressions of fear (P = 0.03 corrected), as did severe patients for disgust (P = 0.04 corrected) and irritation (P < 0.01 corrected). In the whole cohort, these performances were associated with decreased episodic memory and anosmia, but not with depressive symptoms, anxiety or post-traumatic stress disorder. Neuroimaging revealed a positive contribution of functional connectivity, notably between the cerebellum and the default mode, somatosensory motor and salience/ventral attention networks. These results highlight the long-term consequences of SARS-Cov-2 infection on the limbic system at both the behavioural and neuroimaging levels.

A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study

BackgroundThere is evidence that both omega-3 long-chain polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and cocoa flavanols can improve cognitive performance in both healthy individuals and in those with memory complaints. However, their combined effect is unknown. ObjectivesTo investigate the combined effect of EPA/DHA and cocoa flavanols (OM3FLAV) on cognitive performance and brain structures in older adults with memory complaints. MethodsA randomized placebo-controlled trial of DHA-rich fish oil (providing 1.1 g/d DHA and 0.4 g/d EPA) and a flavanol-rich dark chocolate (providing 500 mg/d flavan-3-ols) was conducted in 259 older adults with either subjective cognitive impairment or mild cognitive impairment. Participants underwent assessment at baseline, 3 mo, and 12 mo. The primary outcome was the number of false-positives on a picture recognition task from the Cognitive Drug Research computerized assessment battery. Secondary outcomes included other cognition and mood outcomes, plasma lipids, brain-derived neurotrophic factor (BDNF), and glucose levels. A subset of 110 participants underwent structural neuroimaging at baseline and at 12 mo. Results197 participants completed the study. The combined intervention had no significant effect on any cognitive outcomes, with the exception of reaction time variability (P = 0.007), alertness (P < 0.001), and executive function (P < 0.001), with a decline in function observed in the OM3FLAV group (118.6 [SD 25.3] at baseline versus 113.3 [SD 25.4] at 12 mo for executive function) relative to the control, and an associated decrease in cortical volume (P = 0.039). Compared with the control group, OM3FLAV increased plasma HDL, total cholesterol ratio (P < 0.001), and glucose (P = 0.008) and reduced TG concentrations (P < 0.001) by 3 mo, which were sustained to 12 mo, with no effect on BDNF. Changes in plasma EPA and DHA and urinary flavonoid metabolite concentrations confirmed compliance to the intervention. ConclusionsThese results suggest that cosupplementation with ω-3 PUFAs and cocoa flavanols for 12 mo does not improve cognitive outcomes in those with cognitive impairment.This trial was registered at clinicaltrials.gov as NCT02525198.

Processing speed and memory test performance are associated with different brain region volumes in Veterans and others with progressive multiple sclerosis.

Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates. This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes. The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028). Cognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts. Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% (n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0-6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume (R = 0.29, p = 0.01) and total white matter volume (R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness (R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses. Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations.

Clostridium butyricum improves cognitive dysfunction in ICV-STZ-induced Alzheimer's disease mice via suppressing TLR4 signaling pathway through the gut-brain axis.

In recent years, the relationship between gut-brain axis and Alzheimer's disease (AD) attracted increasing attention. The aim of this study is to investigate the therapeutic effect of Clostridium butyricum (CB) on intraventricular injection of streptozotocin (ICV-STZ)-induced mice and the potential mechanisms. ICV-STZ mice were treated with CB by gavage for 21 consecutive days. The pharmacological effect of CB was assessed by behavior test, brain tissue H&E staining and tau protein phosphorylation levels of hippocampus tissues. The expression levels of TLR4, MYD88, NF-κB p65, TNF-α, iNOS, Occludin and ZO-1 in hippocampal and colonic tissues were detected by Western-blot method. 16S rRNA gene sequencing analysis was used to analyze the intestinal microbiota of mice. The results showed that CB improved the cognitive dysfunction of ICV-STZ mice, restored the structure and cell number of hippocampal and cortical neurons, decreased the protein levels of pSer404-tau protein in hippocampal tissues and TLR4, MYD88, NF-κB p65 and iNOS in hippocampal and colonic tissues, and increased the protein levels of Occludin and ZO-1 in colonic tissues. Meanwhile, CB reversed the changes of intestinal microbiota in AD mice. Therefore, the mechanisms of cognitive function and brain pathological changes in AD mice improved by CB may be related to the regulation of TLR4 signaling pathway and intestinal microbiota. This study supports the potential anti-AD effect of CB and initially revealed its pharmacological mechanism of CB, providing a theoretical basis for further clinical application of CB.

Neurometabolic and structural alterations of medial septum and hippocampal CA1 in a model of post-operative sleep fragmentation in aged mice: a study combining 1H-MRS and DTI.

Post-operative sleep disturbance is a common feature of elderly surgical patients, and sleep fragmentation (SF) is closely related to post-operative cognitive dysfunction (POCD). SF is characterized by sleep interruption, increased number of awakenings and sleep structure destruction, similar to obstructive sleep apnea (OSA). Research shows that sleep interruption can change neurotransmitter metabolism and structural connectivity in sleep and cognitive brain regions, of which the medial septum and hippocampal CA1 are key brain regions connecting sleep and cognitive processes. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method for the evaluation of neurometabolic abnormalities. Diffusion tensor imaging (DTI) realizes the observation of structural integrity and connectivity of brain regions of interest in vivo. However, it is unclear whether post-operative SF induces harmful changes in neurotransmitters and structures of the key brain regions and their contribution to POCD. In this study, we evaluated the effects of post-operative SF on neurotransmitter metabolism and structural integrity of medial septum and hippocampal CA1 in aged C57BL/6J male mice. The animals received a 24-h SF procedure after isoflurane anesthesia and right carotid artery exposure surgery. 1H-MRS results showed after post-operative SF, the glutamate (Glu)/creatine (Cr) and glutamate + glutamine (Glx)/Cr ratios increased in the medial septum and hippocampal CA1, while the NAA/Cr ratio decreased in the hippocampal CA1. DTI results showed post-operative SF decreased the fractional anisotropy (FA) of white matter fibers in the hippocampal CA1, while the medial septum was not affected. Moreover, post-operative SF aggravated subsequent Y-maze and novel object recognition performances accompanied by abnormal enhancement of glutamatergic metabolism signal. This study suggests that 24-h SF induces hyperglutamate metabolism level and microstructural connectivity damage in sleep and cognitive brain regions in aged mice, which may be involved in the pathophysiological process of POCD.

Association of sleep duration with cognitive performance and structural brain differences: A large population‐based cross‐sectional study

AbstractBackgroundSleep duration has been linked to dementia risk; however, its association with cognitive functioning in specific domains and the underlying mechanisms remain unclear. We aimed to examine the association of sleep duration with cognitive performance and structural brain differences using magnetic resonance imaging (MRI).MethodsWithin the UK Biobank, 43,255 dementia‐free participants (aged ≥44, 52.0% female) were included. Self‐reported sleep duration (hours/day) was recorded following a structured questionnaire and trichotomized as short (≤5), normal (6‐8), and long (≥9) sleep. Cognitive functioning (including fluid intelligence, pairs matching, reaction time, and numeric memory) was evaluated using a touchscreen test battery. MRI scans were performed, and total and regional brain volumes (including white matter, gray matter, and hippocampus), and white matter hyperintensities (WMH) were measured. Data on lifestyle factors and medical conditions were collected. Data were analyzed using linear regression.ResultsOf all participants, 2092 (4.8%) had short, 38,041 (87.9%) had normal, and 3122 (7.2%) had long sleep. In multi‐adjusted linear regression, compared with normal sleep duration, both short (β: ‐0.14, 95%, CI: ‐0.19 to ‐0.10) and long (β: ‐0.06, 95% CI: ‐0.10 to ‐0.03) sleep were related to poorer performance in fluid intelligence. Long sleep was also associated with poorer numeric memory (β: ‐0.06, 95% CI: ‐0.10 to ‐0.01). In MRI data analyses, compared with normal sleep duration, short sleep was related to a smaller hippocampus volume (β: ‐0.05, 95% CI: ‐0.09 to ‐0.01), while long sleep was associated with smaller total brain (β: ‐4.51, 95% CI: ‐6.82 to ‐2.21), gray matter (β: ‐3.32 95% CI: ‐4.70 to ‐1.94), and hippocampus (β: ‐0.06, 95% CI ‐0.09 to ‐0.02) volumes, but greater WMH (β: 0.05, 95% CI: 0.01 to 0.08), after adjusting for confounders.ConclusionsShort and long sleep durations are associated with poorer cognitive performance in different domains. Short sleep may indicate neurodegeneration, and long sleep may implicate both neurodegenerative and vascular changes in the brain.

How white matter hyperintensities impacts Alzheimer’s disease and frontotemporal dementia across underrepresented Latin American samples

AbstractBackgroundWhite matter hyperintensities (WMH) are frequently observed on MRI scans of older people. Usually interpreted as a sign of cerebrovascular disease (CVD), they are also associated with increased risk of cognitive impairment and dementia. While WMH and CVD are highly prevalent in Alzheimer’s disease (AD), this has been less studied in behavioral variant frontotemporal dementia (bvFTD), letting alone their study in underrepresented populations with increased CVD. Here, we investigated WMH in AD and bvFTD patients in Latin America (Argentina, Chile and Colombia), a region with high prevalence of CVD. We analyzed total volume and regional distribution of WMH and its association with cognitive impairment and brain lacunes, a marker of CVD.MethodA total of 66 patients (43 AD, 23 bvFTD) and 66 controls (CN) from the ReDLat consortium underwent high‐resolution brain MRI and neuropsychological examination. WMH were extracted from Flair images using automated segmentation algorithms to perform analyses of total volume and spatial distribution. Brain lacunes were visually quantified from T1 and Flair images. Group differences in total and regional WMH volume and associations with different cognitive domains, age, and brain lacunes were examined.ResultTotal and regional WMH volumes were significant larger in AD patients compared to CN and to bvFTD. No differences were found between CN and bvFTD. Only in AD, regional WMH load correlated with worse performance in a particular executive functioning task. No differences were found in the proportion of lacunes among groups nor in the total load of WMH of subjects with or without lacunes. In CN and AD, but not FTD, there was a positive correlation between total WMH volume and age, with a differential topographic distribution with a selective involvement of the bilateral cingulum‐hippocampus bundle in AD.ConclusionEnhanced WMH was observed in AD but not in FTD. WMH loading in specific brain regions contribute to domain‐specific cognitive deficits in AD. WMH could be partially independent of vascular pathology (it was unrelated to brain lacunes) suggesting a specific neurodegenerative origin in AD. The typical earlier onset of brain abnormalities in FTD could mask the age‐related increase in WMH.

Examining factors that influence African‐Americans and Blacks’ participation in Alzheimer’s biomarker research

AbstractBackgroundAfrican Americans and Blacks in the US are less likely to engage in Alzheimer’s disease (AD) research studies, despite having two to three times higher risks of developing AD compared to Whites. Understanding the various factors influencing African Americans and Blacks’ participation in AD research, especially studies that involve biomarkers, is important for increasing equity in AD research, and advancing AD diagnosis and treatment for diverse populations.MethodStudy participants included 164 community‐dwelling African Americans and Blacks in the Indianapolis metropolitan area, aged 55 and older, and who had no prior participation in AD research. Participants were administered a 24‐item survey to examine their knowledge of AD, willingness to participate in biomarker research procedures (genetic testing, brain MRI, and PET Scan), and views of incentives for participation.ResultMost participants were female (68%) and had less than 16 years of education (71%). About half were 65 years old or older. Most participants (84%) reported that they did not know what caused AD or how to manage it, and only 43% were aware that “Black people are at higher risk of developing dementia, including Alzheimer’s disease, compared to Whites.” Most participants were willing to do or consider participating in biomarker procedures common in AD research studies (90% genetic testing, 86% MRI, and 82% PET scan).The majority (85%) were agreeable to future contact for research participation. Most participants viewed return of test results, particularly from cognitive testing (81%) and brain scans (82%), and information about brain health (72%) as incentives to participate in research.ConclusionOur findings revealed that older African‐American and Black participants are willing to engage in Alzheimer’s disease biomarker research study procedures. They also viewed knowledge (in the form of return of results and information about brain health) as a major incentive for participation. Our findings suggest that future outreach and recruitment strategies tailored towards African Americans and Blacks may benefit from focusing on the value of knowledge these studies can provide to participants. We also identified opportunities to educate African Americans and Blacks about their increased risk for AD and the causes and prevention of AD.

Brain asymmetry: a novel perspective on hemispheric network

Brain asymmetry, involving structural and functional differences between the two hemispheres, is a major organizational principle of the human brain. The structural and functional connectivity within each hemisphere defines the hemispheric network or connectome. Elucidating left-right differences of the hemispheric network provides opportunities for brain asymmetry exploration. This review examines the asymmetry in the hemispheric white matter and functional network to assess health and brain disorders. In this article, the brain asymmetry in structural and functional connectivity including network topologies of healthy individuals, involving brain cognitive systems and the development trend, is highlighted. Moreover, the abnormal asymmetry of the hemispheric network related to cognition changes in brain disorders, such as Alzheimer’s disease, schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder, and bipolar disorder, is presented. This review suggests that the hemispheric network is highly conserved for measuring human brain asymmetries and has potential in the study of the cognitive system and brain disorders.

Divergent patterns of cognitive deficits and structural brain alterations between older adults in mixed‐sex and same‐sex relationships

AbstractBackgroundSexual minority (SM) or lesbian, gay, bisexual, and queer older adults experience health disparities that may cause cognitive decline. Several studies have reported higher rates of subjective cognitive complaints in SM older adults, but evidence of increased cognitive decline has been inconsistent. One study found that older adults with Alzheimer’s disease (AD) in same‐sex relationships (SSR), compared to mixed‐sex relationships (MSR), had more severe neuropsychiatric symptoms associated with atrophy in fronto‐temporal regions. We sought to compare behavioral and structural brain parameters of SSR and MSR older adults and evaluate their impact on cognitive performance.MethodNational Alzheimer’s Coordinating Center data were selected according to the following inclusion criteria: 55+ years of age, presence of a co‐participant, and availability of brain volume and mean thickness data. Clinical Dementia Rating® (CDR®) scores were used to assign participants to cognitively impaired (CI; CDR®≥0.5) or cognitively unimpaired (CU; CDR®&lt;0.5) groups. We identified 1076 MSR (583 CU) and 38 SSR (25 CU) participants with Mini‐Mental State Exam (MMSE) and Neuropsychiatric Inventory Questionnaire (NPI‐Q) data within six months of a study visit. Comprehensive neuropsychological test results were available for a sub‐sample of participants (940 MSR and 33 SSR). General linear models were used to investigate the effects of diagnosis, relationship, and NPI‐Q scores on structural and cognitive outcomes.ResultThe MSR group presented with more impairments. Diagnosis‐by‐relationship interaction effects were observed for brain parameters: 1) CI‐MSR had more atrophy in occipital, medio‐temporal, and frontal areas; 2) CU‐MSR had reduced volume/thickness in orbito‐frontal, insular, and anterior cingulate cortices. The MSR groups had greater executive, memory, and language deficits. Neuropsychiatric symptom severity was negatively associated with volume and thickness of bilateral temporo‐cingulate areas and total MMSE scores in the MSR groups only.ConclusionMSR older adults had greater cognitive and behavioral impairments compared to SSR older adults. CI‐MSR had greater grey matter atrophy in areas particularly affected by AD (i.e., medio‐temporal regions). Our results suggest that SM older adults may present with less neurocognitive impairment on comprehensive assessment, despite previous evidence of subjective complaints. Further investigations are needed to clarify factors influencing cognitive decline in older SM.

Cognitive function and brain structure correlates in individuals with subjective cognitive decline: Voxel‐based morphometry results from a lifestyle intervention to prevent Alzheimer’s disease (PENSA study)

AbstractBackgroundInterventions based on the modification of several lifestyle factors have provided promising results to maintain cognitive function in late/middle‐aged individuals at higher risk of developing Alzheimer’s disease (AD). Framed under the WW‐FINGERS network, the PENSA clinical trial is focused on the prevention of cognitive decline in individuals with subjective cognitive decline who are also APOEε4 carriers. It consists of a 12‐month multimodal lifestyle intervention supplemented with EGCG, a natural flavonoid from green tea. In this study, we looked for the brain structure correlates of cognitive performance for PENSA participants at baseline.MethodsOne hundred thirty‐one (N = 131) participants of the PENSA study at baseline [Table 1] with valid T1w, T2w and FLAIR MRI scans were included. They underwent a neuropsychological assessment battery consisting of the modified Alzheimer Disease Cooperative Study ‐ Preclinical Alzheimer Cognitive Composite (ADCS‐PACC‐Plus‐exe) that includes MMSE, Free and Cued Selective Reminding Test (FCSRT), Delayed Recall Logical Memory (DRLM), Five Digits Test, Digit Symbol Substitution Test, and Stroop. Additional cognitive measurements were obtained from semantic verbal fluency (SVF), Boston Naming Test, digit span subtest, visual puzzle subtest (VPT) and the Montreal Cognitive Assessment. FLAIR images were used to segment white matter hyperintensities and perform a lesion filling procedure in T1w and T2w images. These two later modalities were then entered into a multimodal segmentation in the SPM12 voxel‐based morphometry pipeline. Associations between test scores and grey matter volumes (GMv) were sought (p&lt;0.001) including age, sex, education, and total intracranial volume as confounders.ResultsA positive association was found (p uncorr &lt;0.001; k&gt;200) between GMv and ADCS‐PACC‐Plus‐exe composite [Figure 1] in the bilateral hippocampus, amygdala, entorhinal and parahippocampal gyri. Additionally, positive correlations (p uncorr &lt;0.001; k&gt;200) were found between GMv and FCSRT, DRLM, VPT and SVF tests albeit in less consistent regional patterns. No associations were found between GMv and the remaining tests.ConclusionIn a sample at high risk of developing AD, the ADCS‐PACC‐Plus‐exe composite is associated with GMv in brain areas known to be affected in AD. These results suggest that the ADCS‐PACC‐Plus‐exe composite might be sensitive to detect subtle cognitive changes in cognitively unimpaired at‐risk individuals.

Kernel flow and the eye‐ brain connectome: Study design and objectives

AbstractBackgroundMore evidence suggests how the eye health may be crucial in older adults at risk of developing cognitive impairment (CI) and Alzheimer’s disease (AD). Ocular conditions and AD share several common factors, including older age behavioral and cardiometabolic disease. Poor vision can lead to reduced activation of central sensory pathways, which is associated with higher cognitive load and brain structure damage. We showed that CI is not limited to the brain but also affects the retina. However, despite recent advances in neuroimaging biomarkers (e.g., PET diagnostics), there remains a need for more readily available and affordable diagnostic testing for AD risk. While blood flow within the optic nerve head can be quantified using advanced optical imaging technologies, it is essential to measure what is going on in the brain at the same time.MethodWe propose a cross‐sectional and longitudinal, observational study evaluating structural and functional biomarkers of the retina and brain associated with AD disease risk and/or progression. The study objective is to collect structural and functional data of the retina and brain to facilitate the discovery of reliable and sensitive multimodal biomarkers of AD disease risk and/or progression. We will examine participants (N = 200) aged 55‐80; 50 cognitively healthy (CH), 50 with preclinical AD, 50 with mild CI (MCI), and 50 with mild AD. Assessments will include neuropsychological testing, medical/functional assessment, retinal imaging, brain activity, electroretinography, pupillometry, and contrast sensitivity. We will use a wearable, whole‐head coverage time‐domain functional near‐infrared spectroscopy system (Kernel Inc) to measure local changes in blood oxygenation and electroencephalography.ResultThe eye‐brain connectome is integral in understanding pathology in neurodegenerative diseases. We aim to use the eye‐brain data to develop screening and monitoring tools to identify and track AD risk and severity.ConclusionThis study will overcome limitations for performing functional brain imaging due to the lack of portability and user‐friendliness of neuroimaging devices. Our eye‐brain multimodal biomarker study could also facilitate a novel application for diagnostic assessment and therapeutic intervention to target neuroanatomical sites compromised early in AD, leading to a more robust technique to identify high‐risk individuals before cognitive decline with sufficient sensitivity and specificity.

Associations between peripheral hearing ability at age 70, brain atrophy and cognitive decline in adults born in the same week of 1946

AbstractBackgroundPeripheral hearing impairment has been proposed as a risk factor for dementia. However, the relationship between hearing ability, neurodegeneration and cognitive decline, and the extent to which pathological processes associated with increased risk of specific causes of dementia, such as β‐amyloid and small vessel disease, influence these relationships, is unclear.MethodData were analysed from 287 cognitively normal adults born in the same week of 1946 who underwent pure tone audiometry testing at baseline (mean age = 70.6 years), with cognitive assessment and brain imaging at baseline and at follow‐up on average 2.4 years later. Peripheral hearing impairment was defined as a pure tone average of greater than 25 decibels in the best hearing ear. Rates of change for whole brain, hippocampal and ventricle volume were estimated from structural MRI using the Boundary Shift Integral. Cognition was assessed using the Pre‐clinical Alzheimer’s Cognitive Composite. Regression models were performed to evaluate how baseline hearing impairment associated with subsequent brain atrophy and cognitive decline after adjustment for a range of variables including baseline β‐amyloid deposition (assessed using florbetapir‐PET) and baseline small vessel disease burden (estimated using white matter hyperintensity volume).Results111 out of 287 participants were defined as having peripheral hearing impairment. Hearing impaired individuals demonstrated faster rates of whole brain atrophy (p = 0.031 – figure/table 1) compared with those with normal hearing. Peripheral hearing impairment did not predict change in PACC performance, but there was evidence of an interaction between hearing impairment and whole brain atrophy rates in terms of effect on change in PACC performance. Specifically, faster rates of whole brain atrophy predicted greater cognitive decline in participants with hearing impairment (p = 0.004), whilst there was no evidence of an association between cognitive change and atrophy in participants with preserved hearing (figure/table 2). There was no evidence that β‐amyloid deposition or white matter hyperintensity volume modified these relationships.ConclusionWe present evidence of associations between peripheral hearing ability at age 70, brain atrophy and cognitive decline independent of β‐amyloid and small vessel disease, suggesting hearing may associate with brain health via mechanisms distinct from those typically implicated in pre‐clinical Alzheimer’s disease and vascular cognitive impairment.

The association among plasma p‐tau181, cognitive progression and structural brain change in early Alzheimer’s disease

AbstractBackgroundPlasma levels of phosphorylated tau 181 (p‐tau181) is one of the potential blood‐based biomarkers for the diagnosis of Alzheimer’s disease (AD). However, the association among plasma p‐tau181 and cognitive progression and structural brain change still needs to be investigated.MethodAD and mild cognitive impairment (MCI) patients diagnosed with a multidisciplinary consensus meeting were recruited. Cognitive function was assessed at baseline and at annual follow‐ups. Plasma p‐tau181 levels at baseline were measured using Quanterix SIMOA kits. The regional cortical thickness and volumes of baseline brain MRI were measured using the FreeSurfer image analysis suite. T‐tests and multiple regression were used for analyses. FDR tests were performed for multiple comparisons.ResultA total of 162 AD and 19 MCI patients were recruited (mean age = 77.4 ± 7.3 years, 42% male, 37% APOE ɛ4 carrier, and mean MMSE = 20 ± 5.4). There were 137 patients (75.7%) having at least two annual follow‐up and the mean follow‐up time was 2.1 ± 0.4 years. The baseline plasma p‐tau181 levels were correlated with the rates of MMSE decline per year (r = 0.284, p &lt; 0.001). After adjusting for age, gender, education, APOE ɛ4 status and baseline MMSE, the baseline plasma p‐tau181 levels were still correlated with the yearly MMSE decline (β = 0.292, p = 0.001) and was able to predict MMSE decline&gt;3 per year (OR = 4.03, 95% CI 1.47–11.05). There were 152 patients (135 AD and 17 MCI) with valid brain MRI. The cross‐sectional analyses with adjustments of age, gender, education and APOE ɛ4 status showed significant association between plasma p‐tau181 levels and left hippocampus volume (β = ‐0.205, p = 0.010), right hippocampus volume (β = ‐0.213, p = 0.009) and right middle temporal thickness (β = ‐0.292, p &lt; 0.001).ConclusionHigher plasma p‐tau181 levels were associated with the faster rate of MMSE decline in AD and MCI patients as well as the decreased volume and cortical thickness of several AD‐specific brain areas. Our study suggested that the plasma p‐tau181 could be a potential biomarker for tracking cognitive decline and reflecting structural brain changes in AD and MCI patients.

SORL1 rs1699102 Moderates the Effect of Sex on Language Network.

Language ability differs between the sexes. However, it is unclear how this sex difference is moderated by genetic factors and how the brain interacts with genetics to support this specific language capacity. Previous studies have demonstrated that the sorting protein-related receptor (SORL1) polymorphism influences cognitive function and brain structure differently in males and females and is associated with Alzheimer's disease risk. The aim of this study was to investigate the effects of sex and the SORL1 rs1699102 (CC versus T carriers) genotype on language. 103 non-demented Chinese older adults from Beijing Aging Brain Rejuvenation Initiative (BABRI) database were included in this study. Participants completed language tests, T1-weighted structural magnetic resonance imaging (MRI) and resting-state functional MRI. Language test performance, gray matter volume, and network connections were compared between genotype and sex groups. The rs1699102 polymorphism moderated the effects of sex on language performance, with the female having reversed language advantages in T carriers. The T allele carriers had lower gray matter volume in the left precentral gyrus. The effect of sex on language network connections was moderated by rs1699102; male CC homozygotes and female T carriers had higher internetwork connections, which were negatively correlated with language performance. These results suggest that SORL1 moderates the effects of sex on language, with T being a risk allele, especially in females. Our findings underscore the importance of considering the influence of genetic factors when examining sex effects.

Eliciting brain waves of people with cognitive impairment during meditation exercises using portable electroencephalography in a smart-home environment: a pilot study.

Meditation imparts relaxation and constitutes an important non-pharmacological intervention for people with cognitive impairment. Moreover, EEG has been widely used as a tool for detecting brain changes even at the early stages of Alzheimer's Disease (AD). The current study investigates the effect of meditation practices on the human brain across the AD spectrum by using a novel portable EEG headband in a smart-home environment. Forty (40) people (13 Healthy Controls-HC, 14 with Subjective Cognitive Decline-SCD and 13 with Mild Cognitive Impairment-MCI) participated practicing Mindfulness Based Stress Reduction (Session 2-MBSR) and a novel adaptation of the Kirtan Kriya meditation to the Greek culture setting (Session 3-KK), while a Resting State (RS) condition was undertaken at baseline and follow-up (Session 1-RS Baseline and Session 4-RS Follow-Up). The signals were recorded by using the Muse EEG device and brain waves were computed (alpha, theta, gamma, and beta). Analysis was conducted on four-electrodes (AF7, AF8, TP9, and TP10). Statistical analysis included the Kruskal-Wallis (KW) nonparametric analysis of variance. The results revealed that both states of MBSR and KK lead to a marked difference in the brain's activation patterns across people at different cognitive states. Wilcoxon Signed-ranks test indicated for HC that theta waves at TP9, TP10 and AF7, AF8 in Session 3-KK were statistically significantly reduced compared to Session 1-RS Z = -2.271, p = 0.023, Z = -3.110, p = 0.002 and Z = -2.341, p = 0.019, Z = -2.132, p = 0.033, respectively. The results showed the potential of the parameters used between the various groups (HC, SCD, and MCI) as well as between the two meditation sessions (MBSR and KK) in discriminating early cognitive decline and brain alterations in a smart-home environment without medical support.

Impact of Diet and Exercise Interventions on Cognition and Brain Health in Older Adults: A Narrative Review.

The ability to preserve cognitive function and protect brain structure from the effects of the aging process and neurodegenerative disease is the goal of non-pharmacologic, lifestyle interventions focused on brain health. This review examines, in turn, current diet and exercise intervention trends and the collective progress made toward understanding their impact on cognition and brain health. The diets covered in this review include the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), ketogenic diet, intermittent fasting, and weight loss management. The exercise approaches covered in this review include endurance, resistance, combined exercise programs, yoga, tai chi, and high-intensity interval training. Although valuable evidence is building concerning how diet and exercise influence cognitive performance and brain structure, many of the open questions in the field are concerned with why we see these effects. Therefore, more strategically designed intervention studies are needed to reveal the likely multiple mechanisms of action in humans.

NT-proBNP and changes in cognition and global brain structure: the Rotterdam Study.

To investigate the association between NT-proBNP and changes in cognition and global brain structure. In the Rotterdam Study, baseline NT-proBNP was assessed at baseline from 1997 to 2008. Between 1997-2016, participants without dementia or stroke at baseline (n= 9,566) had repeated cognitive tests (every 3-6 years) for global cognitive function, executive cognitive function, fine manual dexterity, and memory. Magnetic resonance imaging of the brain was performed repeatedly at re-examination visits between 2005 and 2015 for 2,607 participants to obtain brain volumes, focal brain lesions, and white matter microstructural integrity as measures of brain structure. Among 9,566 participants (mean age 65.1±9.8 years), 5,444 (56.9%) were women, and repeated measures of cognition were performed during a median follow-up time of 5.5 years (range = 1.1-17.9), of whom 2,607 participants completed at least one brain imaging scans. Higher levels of NT-proBNP were associated with a faster decline of scores in the global cognitive function (P value = 0.003), and the Word-Fluency test (P value = 0.003), but were not related to a steeper deterioration in brain volumes, global fractional anisotropy and mean diffusivity, as indicators of white matter microstructural integrity, or focal brain lesions. Higher baseline NT-proBNP levels were associated with a faster decline in cognition, however, no association with global brain structure was found.