Early Stages Of Cognitive Decline Research Articles

Associations of high-sensitivity C-reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementia.

Inflammation is becoming increasingly recognised as a core feature of dementia with evidence indicating that its role may vary and adapt across different stages of the neurodegenerative process. This study aimed to investigate whether the associations of high-sensitivity C-reactive protein (hs-CRP) with neuropsychological performance (verbal memory, executive function, processing speed) and cerebral white matter hyperintensities (WMHs) differed between older adults with subjective cognitive decline (SCD; n=179) and mild cognitive impairment (MCI; n=286). Fasting serum hs-CRP concentrations were grouped into low (<1.0mg/L), moderate (1.0-3.0mg/L), and high (>3.0-10.0mg/L). Structural MRI scans were used to estimate WMH lesion volumes in the whole brain, as well as periventricular, deep white matter, and frontal regions. After adjusting for relevant demographic and clinical factors, multiple regression analyses revealed that in participants with SCD, high hs-CRP concentrations were significantly associated with poorer executive function (β[95% CI]=-.20[-.65, -.04], p=.025) and processing speed (β[95% CI]=-.19[-.53, .00], p=.048). Exploratory analyses suggested that this effect may be specific to APOE-ε4 non-carriers only. There were no significant associations between hs-CRP and neuropsychological outcomes in those with MCI. Hs-CRP was not associated with WMH volumes. Our findings suggest that hs-CRP may be involved in early disruptions to cerebral frontal-subcortical pathways, particularly in APOE-ε4 non-carriers, though this association may be independent of white matter lesions. In the earliest stages of cognitive decline where subjective complaints are paramount, addressing inflammation may offer potential benefits for supporting cognitive health.

MusiMentes: Home-based musical interventions for people with mild cognitive impairment and mild dementia, a randomized controlled trial protocol

Mild Cognitive Impairment (MCI) and Mild Dementia (MD) represent a growing challenge in Latin America, with an estimated prevalence between 11-28% in people over 65 years. Musical interventions have shown potential benefits for cognitive functioning and emotional well-being in this population. Objective: To evaluate the efficacy of the "MusiMentes" home-based musical intervention protocol on cognitive functioning and emotional well-being in patients with MCI and MD, as well as its impact on the patient-caregiver relationship. Methods: Single-blind, randomized controlled trial with 50 outpatients (50-80 years) diagnosed with MCI or MD and their primary caregivers. The experimental group will perform active and personalized musical interventions ("MusiMentes"), while the control group will engage in passive music listening, both for 30 minutes, three times per week for 12 weeks. Cognitive functioning (MOCA, MIS), executive functions (TMT, DST), emotional well-being (EADG, PANAS, WHOQOL-BREF, VAMS-R), and patient-caregiver relationship (SQCRC) will be evaluated at three time points: pre-intervention, post-intervention, and three-month follow-up. Relevance: This study will provide evidence on the effectiveness of home-based musical interventions in early stages of cognitive decline, contributing to the development of accessible and personalized therapeutic strategies in the Latin American context.

Cholinergic Basal Forebrain Integrity and Cognition in Parkinson's Disease: A Reappraisal of Magnetic Resonance Imaging Evidence.

Cognitive impairment is a well-recognized and debilitating symptom of Parkinson's disease (PD). Degradation in the cortical cholinergic system is thought to be a key contributor. Both postmortem and in vivo cholinergic positron emission tomography (PET) studies have provided valuable evidence of cholinergic system changes in PD, which are pronounced in PD dementia (PDD). A growing body of literature has employed magnetic resonance imaging (MRI), a noninvasive, more cost-effective alternative to PET, to examine cholinergic system structural changes in PD. This review provides a comprehensive discussion of the methodologies and findings of studies that have focused on the relationship between cholinergic basal forebrain (cBF) integrity, based on T1- and diffusion-weighted MRI, and cognitive function in PD. Nucleus basalis of Meynert (Ch4) volume has been consistently reduced in cognitively impaired PD samples and has shown potential utility as a prognostic indicator for future cognitive decline. However, the extent of structural changes in Ch4, especially in early stages of cognitive decline in PD, remains unclear. In addition, evidence for structural change in anterior cBF regions in PD has not been well established. This review underscores the importance of continued cross-sectional and longitudinal research to elucidate the role of cholinergic dysfunction in the cognitive manifestations of PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Associations of C‐reactive protein and homocysteine with neuropsychological outcomes in older adults at risk of dementia

AbstractBackgroundInflammation is becoming increasingly recognised as a core feature of dementia and neurodegenerative processes. High‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine are blood‐based markers of non‐specific inflammation used in clinical settings. This study aimed to 1) investigate the associations of hs‐CRP and homocysteine on neuropsychological performance (i.e. verbal memory, executive function, processing speed) in older adults attending a memory clinic; and 2) examine whether these associations differed for individuals at varying risk stages of dementia, i.e. with subjective cognitive decline (SCD) vs. mild cognitive impairment (MCI).MethodWe recruited older adults aged ≥ 50 years with new‐onset cognitive concerns without dementia. A fasting blood sample was used to obtain concentrations of serum hs‐CRP (mg/L) and plasma homocysteine (µmol/L). Hs‐CRP levels were grouped into low &lt;1.0mg/L, moderate 1.0‐3.0mg/L, and high risk &gt;3.0‐10.0 mg/L. A standardised neuropsychological assessment was conducted by a clinical neuropsychologist, and composite scores for each neuropsychological outcome were calculated as an average of z‐scores of all tests within the same domain. Classifications of MCI were determined by clinician consensus as having objective impairments in neuropsychological tests (≥1.5SDs below normative scores). Multiple regression analyses were conducted, adjusting for relevant demographic and clinical factors.ResultThe final sample consisted of 423 participants (Mean age = 67.37 years [SD = 8.15], 63.1% female, mean MMSE = 28.95 [SD = 1.35]), who were classified as either having SCD (n = 158) or MCI (n = 265). Hs‐CRP and homocysteine concentrations did not differ between SCD and MCI groups. In participants with SCD, high‐risk CRP concentrations were significantly associated with poorer executive function (β = ‐.226, 95% CI = [‐0.692, ‐0.059], p = .020) and processing speed (β = ‐.212, 95% CI = [‐0.584, ‐0.025], p = .033). There were no significant associations between CRP and neuropsychological outcomes in those with MCI, or in the total sample. Homocysteine was not associated with cognitive outcomes.ConclusionCRP may be involved in early disruptions to cerebral frontal‐subcortical pathways. Targeting inflammation in the earliest stages of cognitive decline, where subjective complains are paramount, may be a viable strategy for prevention.

Potential Cognitive Decline Linked to Electronegative L5 in Type 2 Diabetes: A Holo-Hilbert Spectral Analysis

Plain Language SummaryPeople with type 2 diabetes have a higher chance of experiencing cognitive problems. We wanted to find out if a specific type of an electronegative low-density lipoprotein cholesterol called L5 could be linked to these cognitive issues. To do this, we studied 68 people with type 2 diabetes. Fifteen had normal cognition, 39 had mild cognitive impairment, and 14 had Alzheimer’s disease. We used a test called the Cognitive Abilities Screening Instrument to check their cognitions. We also used a novel method called Holo-Hilbert spectral analysis (HHSA) to look at brain activity using electroencephalography (EEG). This helped us see how L5 might be affecting the brain. What we found was interesting. People with higher levels of L5 were more likely to have cognitive problem, including mild cognitive impairment and Alzheimer’s disease. We also found that higher levels of L5 were associated with poorer performance on cognitive tests, especially in tasks requiring concentration. We noticed that as L5 levels went up, brain activity changed in a way that corresponded to degeneration. However, this relationship between L5 and cognition was not the same for everyone. It seemed to be different depending on how advanced their cognitive problems were. In simple terms, our study suggests that L5 could play a role in causing cognitive problems for people with type 2 diabetes, particularly in the early stages of cognitive decline. And by using new methods like HHSA, we can better understand how L5 affects the brain.

Association of longitudinal changes in 24-h blood pressure level and variability with cognitive decline.

A high office blood pressure (BP) is associated with cognitive decline. However, evidence of 24-h ambulatory BP monitoring is limited, and no studies have investigated whether longitudinal changes in 24-h BP are associated with cognitive decline. We aimed to test whether higher longitudinal changes in 24-h ambulatory BP measurements are associated with cognitive decline. We included 437 dementia-free participants from the Maracaibo Aging Study with prospective data on 24-h ambulatory BP monitoring and cognitive function, which was assessed using the selective reminding test (SRT) and the Mini-Mental State Examination (MMSE). Using multivariate linear mixed regression models, we analyzed the association between longitudinal changes in measures of 24-h ambulatory BP levels and variability with cognitive decline. Over a median follow-up of 4 years (interquartile range, 2-5 years), longitudinal changes in 24-h BP level were not associated with cognitive function ( P ≥ 0.09). Higher longitudinal changes in 24-h and daytime BP variability were related to a decline in SRT-delayed recall score; the adjusted scores lowered from -0.10 points [95% confidence interval (CI), -0.16 to -0.04) to -0.07 points (95% CI, -0.13 to -0.02). We observed that a higher nighttime BP variability during follow-up was associated with a decline in the MMSE score (adjusted score lowered from -0.08 to -0.06 points). Higher 24-h BP variability, but not BP level, was associated with cognitive decline. Prior to or in the early stages of cognitive decline, 24-h ambulatory BP monitoring might guide strategies to reduce the risk of major dementia-related disorders including Alzheimer's disease.

Cognitive Stimulation with Music in Older Adults with Cognitive Impairment: A Scoping Review.

The use of music in cognitive interventions represents a possibility with potential worthy of further investigation in the field of aging, both in terms of prevention from dementia, in the phase of mild cognitive impairment, and in the treatment of overt dementia. Currently, the types of music-based interventions proposed in the literature are characterized by wide heterogeneity, which is why it is necessary to clarify which interventions present more evidence of effectiveness in stimulating different cognitive domains. The study was conducted in accordance with PRISMA guidelines for scoping reviews. By searching two different databases, PubMed and the Web of Science, all studies evaluating the cognitive effects of music-based interventions on people at early stages of cognitive decline (MCI or mild-to-moderate dementia) were selected. The study selection included a total of 28 studies involving n = 1612 participants (mean age ranged from 69.45 to 85.3 years old). Most of the studies analyzed agree with the observation of an improvement, or at least maintenance, of global cognitive conditions (mainly represented by the results of the MMSE test) following music-based interventions, together with a series of other positive effects on verbal fluency, memory, and executive processes. The results of this review suggest the introduction of music-based interventions as complementary approaches to usual cognitive treatments. Also, the use of standardized and well-defined protocols, in addition to strong methodological research approaches, is suggested. Music-based interventions are recommended in the early stages of dementia, in MCI, and in a preventive sense in healthy older adults.

Subjective cognitive decline in healthy older adults is associated with altered processing of negative versus positive feedback in a probabilistic learning task.

Older adults who worry about their own cognitive capabilities declining, but who do not show evidence of actual cognitive decline in neuropsychological tests, are at an increased risk of being diagnosed with dementia at a later time. Since neural markers may be more sensitive to early stages of cognitive decline, in the present study we examined whether event-related potential responses of feedback processing, elicited in a probabilistic learning task, differ between healthy older adults recruited from the community, who either did (subjective cognitive decline/SCD-group) or did not report (No-SCD group) worry about their own cognition declining beyond the normal age-related development. In the absence of group differences in learning from emotionally charged feedback in the probabilistic learning task, the amplitude of the feedback-related negativity (FRN) varied with feedback valence differently in the two groups: In the No-SCD group, the FRN was larger for positive than negative feedback, while in the SCD group, FRN amplitude did not differ between positive and negative feedback. The P3b was enhanced for negative feedback in both groups, and group differences in P3b amplitude were not significant. Altered sensitivity in neural processing of negative versus positive feedback may be a marker of SCD.

Cognitive Screening for Mild Cognitive Impairment: Clinician Perspectives on Current Practices and Future Directions.

This study surveyed 51 specialist clinicians for their views on existing cognitive screening tests for mild cognitive impairment and their opinions about a hypothetical remote screener driven by artificial intelligence (AI). Responses revealed significant concerns regarding the sensitivity, specificity, and time taken to administer current tests, along with a general willingness to consider adopting telephone-based screening driven by AI. Findings highlight the need to design screeners that address the challenges of recognizing the earliest stages of cognitive decline and that prioritize not only accuracy but also stakeholder input.

Skeletal Muscle Mitochondrial Response to Diet Differs by Genotype and Sex in an Alzheimer’s Disease Mouse Model

Introduction: Skeletal muscle mass is reduced in the early stages of cognitive decline. Apolipoprotein ε4 ( APOE4) is the most prevalent genetic risk factor for Alzheimer’s disease (AD) and is associated with faster motor decline in cognitively healthy individuals. APOE4 also increases the risk of insulin resistance and cardiovascular disease, conditions associated with altered bioenergetic function in muscle. However, no studies have examined the role of APOE4 in modulating muscle physiology and the impact this would have on cognitive function. We sought to determine if APOE4 affects skeletal muscle mitochondrial metabolism in response to a high-fat diet (HFD) and if this is reflected in whole-body metabolism. We also examined the role of sex since APOE4 carriers who are female are more likely to develop AD. Methods: Male and female APOE3 (n=32) and APOE4 (n= 29) targeted-replacement mice on a C57BL/6 background purchased from Taconic were fed a standard chow diet until 4 months old. Mice were then switched to a low-fat diet (LFD, 10% kcal fat) or HFD (45% kcal fat) until sacrifice. Glucose tolerance was tested at 7 months by administering an intraperitoneal glucose injection of 1g/kg lean mass. Blood glucose was measured before and 15, 30, 45, 60, 90 and 120 minutes after glucose injection. Resting respiratory exchange ratio (RER) was determined using the Promethion Indirect Calorimetry system at 8 months to determine the relative contribution of carbohydrates versus lipids to whole body metabolism. Mice were sacrificed at 9 months and carbohydrate-driven oxygen consumption was measured at basal, state 3 (ADP), state 3 + glutamate, state 3S (succinate) and uncoupled respiratory states in mitochondria isolated from quadriceps tissue on the Oroboros Oxygraph-2k system. Results: Mice fed a HFD had greater glucose area under the curve (p&lt;0.0001) and reduced RER (p= &lt;0.001) compared to mice fed a LFD, regardless of sex or genotype. At the level of skeletal muscle, APOE4 female mice had increased state 3 (p=0.027) and state 3 + glutamate oxygen consumption (p=0.037) on a HFD compared to a LFD while no diet effect was observed in APOE4 males or any APOE3 mice. Conclusion: We provide evidence that female APOE4 mice are susceptible to diet-induced increases in carbohydrate-driven mitochondrial oxygen consumption in muscle. Future studies are needed to determine the underlying mechanism and consequences of increased muscle mitochondrial activity, which could help identify treatment targets in female APOE4 carriers. BHTP T32 AG078114, P30 AG072973 (Chelsea Johnson). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Finger Food Meals as a Means of Improving Mealtimes for People with Motoric Eating Difficulties: A Pilot Study

Motoric eating difficulties affecting the ability to eat according to established norms may result in loss of autonomy, reduced food intake and decreased social interaction. Finger food meals may affect the ability to eat independently and were therefore compared to regular meals for older adults >65 years with major motoric eating difficulties. In this pilot study the screening instrument MEOF-II, including additional questions about use of cutlery and fingers, was used to collect data regarding autonomy, food intake and social interaction through observations. Five women and one man participated in the study. Results showed that finger food meals facilitated autonomous eating since the participants were able to eat independently without relying on help from others. Less energy was spent on eating, which allowed for social interaction. However, finger food meals entail unfamiliar norms and culinary rules which may hinder eating; this is an important factor to consider in the implementation of such meals. Further studies on finger foods for older adults may consider larger and diverse cohorts, including healthy older adults, those with motoric difficulties and those with early stages of cognitive decline. Also, a wider variety of finger foods for specific cultural preferences and situations may be considered.

Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome.

People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials. This large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)42/40, total tau, and neurofilament light chain (NfL) and cognitive (episodic memory, visual-motor integration, and visuospatial abilities) and functional (adaptive behavior) impairments in 260 adults with DS without dementia (aged 25-81 years). In general linear models lower plasma Aβ42/40 was related to lower visuospatial ability, higher total tau was related to lower episodic memory, and higher NfL was related to lower visuospatial ability and lower episodic memory. Plasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest. Plasma Alzheimer's disease (AD) biomarkers correlate with cognition prior to dementia in Down syndrome.Lower plasma amyloid beta 42/40 was related to lower visuospatial abilities.Higher plasma total tau and neurofilament light chain were associated with lower cognitive performance.Plasma biomarkers show potential for tracking early stages of AD symptomology.

The Value of Subjective Olfactometry as a Predictive Biomarker of Neurodegenerative Diseases: A Systematic Review.

Olfactory disorders (ODs) are reported to be an early non-motor sign before the onset of deterioration in neurodegenerative diseases (NDs) such as Alzheimer's and Parkinson's. This systematic revision aims to review the current literature and the value of subjective olfactometry (SO) in the early diagnosis of cognitive decline and NDs. A systematic literature review was conducted following the PRISMA framework. Four different authors reviewed six different databases. The main variables analyzed were olfactory function and cognitive status. The quality of results was evaluated using the Oxford Centre of Evidence-based Medicine Levels. Twenty-one cross-sectional and cohort studies and six meta-analyses were included. Most of them found an association between ODs and NDs. A prevalence of ODs greater than 80% was shown in Parkinson's disease, proportional to the severity of symptoms. In Alzheimer's, ODs were associated with early diagnosis and prognosis. All SO tests employed in the literature showed enough predictive value to correlate with early stages of cognitive decline. SO should be considered a pivotal tool when diagnosing NDs due to their association with early symptoms and prognosis. However, in the current literature, no firm consensus exists on the optimal SO tests and protocols that should be applied to the study of NDs, which prevents the interpretability and comparability of results among studies.

Using 6-CIT, P300 encephalography, and pro-inflammation assessments for screening age-related cognitive decline and exploring associated risk factors in Egyptian elderly

BackgroundThe elderly population is suffering from many mental health problems that are aggravated as a matter of age and cognitive decline is a serious one of them. The aim of the present work is to screen the cognitive performance among a sample of Egyptian elderly volunteers and to investigate the associated risk factors.ResultsA sample of 88 elderly volunteers from both genders was enrolled in the study according to the specified eligibility criteria after signing the approval consent. Medical history and socio-demographic data were collected from all participants in addition to basic clinical examination. Cognitive performance was assessed using the 6-Item Cognitive Impairment Test (6-CIT) while the endogenous event-related potentials (ERP) was measured using P300. The inflammatory biomarkers; TNF-α and COX-2 levels were assessed in serum using ELISA technique in addition to gene expression of TNF-α, PPAR-γ and CD-36 exploration using qRT-PCR. About half (51%) of the sample under investigation showed cognitive problems with scores on the 6-CIT exceeding the normal level. TNF-α serum levels showed positive correlation with P300 latency and correlated negatively with P300 reaction time. Furthermore, serum COX-2 levels correlated positively with P300 reaction time and negatively with P300 amplitude.ConclusionThe study population is showing early signs of cognitive decline that invites attention to the importance of spreading preventive measures against further deterioration. Inflammatory biomarkers under investigation and 6-CIT are suggested to be used in prediction of early stages of cognitive decline among the elderly population.

Clinical importance in Alzheimer’s disease: effects of anchor agreement and disease severity

ObjectivesMethods of evaluating clinically meaningful decline are critical in research on Alzheimer’s disease. A common method of quantifying clinically meaningful change is to calculate an anchor-based minimal clinically important difference (MCID) score. In this approach, individuals who report a meaningful change serve as the “anchors”, and the mean level of change for this group serves as the MCID. In research on Alzheimer’s disease, there are several possible anchors, including patients, knowledgeable observers (e.g., a family member), and clinicians. The goal of this study was to examine the extent to which agreement among anchors impacts MCID estimation and whether this relationship is moderated by cognitive severity status.MethodsAnalyses were completed on a longitudinal sample of 2247 adults, aged 50–103, from the Uniform Data Set. Outcome measures included the Montreal Cognitive Assessment, Clinical Dementia Rating—Sum of Boxes, and Functional Activities Questionnaire.ResultsFor all of the outcomes, the MCID estimate was significantly higher when meaningful decline was endorsed by all of the anchors compared to when there was disagreement among the anchors. In addition, the MCID estimate was higher with increasing severity of cognitive impairment. Finally, cognitive severity status moderated the influence of agreement among anchors on MCID estimation; as disease severity increased, anchor agreement demonstrated less influence on the MCID.ConclusionsMCID estimates based on one anchor may underestimate meaningful change, and researchers should consider the viewpoints of multiple anchors in constructing MCIDs, particularly in the early stages of cognitive decline.

Graph Learning and Deep Neural Network Ensemble for Supporting Cognitive Decline Assessment

Cognitive decline represents a significant public health concern due to its severe implications on memory and general health. Early detection is crucial to initiate timely interventions and improve patient outcomes. However, traditional diagnosis methods often rely on personal interpretations or biases, may not detect the early stages of cognitive decline, or involve invasive screening procedures; thus, there is a growing interest in developing non-invasive methods benefiting also from the technological advances. Wearable devices and Internet of Things sensors can monitor various aspects of daily life together with health parameters and can provide valuable data regarding people’s behavior. In this paper, we propose a technical solution that can be useful for potentially supporting cognitive decline assessment in early stages, by employing advanced machine learning techniques for detecting higher activity fragmentation based on daily activity monitoring using wearable devices. Our approach also considers data coming from wellbeing assessment questionnaires that can offer other important insights about a monitored person. We use deep neural network models to capture complex, non-linear relationships in the daily activities data and graph learning for the structural wellbeing information in the questionnaire answers. The proposed solution is evaluated in a simulated environment on a large synthetic dataset, the results showing that our approach can offer an alternative as a support for early detection of cognitive decline during patient-assessment processes.

Effects of Cognitive‐motor Rhythmic Training on Executive Functions and Motor Performance in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Trial

AbstractIntroductionIn recent years, prevalence of mild cognitive impairment (MCI) has increased in older adults, exacerbating the potential impact on global health. Cognitive‐motor training is an emerging treatment modality with proven benefits in enhancing both physical and cognitive functions. In recent research findings, training of musical rhythmic skills with auditory‐motor synchronization is beneficial to reactivate the brain’s sensorimotor and perceptual regions as well as to improve cognition. However, there is limited research on combining these modalities.ObjectivesThis pilot study aims to develop a pioneer program on cognitive‐motor rhythmic training (CMRT), and to investigate whether the program would improve the executive functions (EF) and hand functions of patients with MCI.MethodologyThirty patients recruited from the Hong Kong Buddhist Hospital were randomized into two groups: (i) an intervention group receiving a 6‐week training program and (ii) a waitlist control group. The program was designed with reference to the rhythm game “Taiko no Tatsujin”, in which precise timed motor responses were required to hit the circular cues against the target zone. The game was designed with progression of difficulty levels and instant feedback. Classical Cantopop songs that were familiar to Hong Kong older adults were selected. Mental flexibility, inhibitory control, working memory, visuospatial memory, verbal fluency, processing speed and problem‐solving were assessed using domain‐specific cognitive tests, while hand dexterity was measured by the Purdue Pegboard Test. Paired t‐test and ANOVA were used to examine the within group difference and the comparison between groups. The level of significance was set at P&lt;0.05.ResultsThe analysis showed significant Time x Group interaction effects in Color Trail Test (p = 0.001), Color Word Stroop Test (P = 0.002), Digit Span Test (P&lt;0.001), Corsi Block‐Tapping Test (P&lt;0.001), Verbal Fluency Test (P&lt;0.001), Symbol Digit Modalities Test (P = 0.015), Maze Test (P&lt;0.001) and the Purdue Pegboard scores (P&lt;0.001) compared to the control group after training.ConclusionsThe 6‐week CMRT program is effective in improving the executive functions and motor performance in patients with MCI. This innovation can serve as an affordable and quality intervention in early stages of cognitive decline.

Suboptimal sleep efficiency and duration predict faster cognitive decline in cognitively unimpaired older adults

AbstractBackgroundResearch indicates a role for suboptimal sleep, in cognitive ageing. An increasing, though inconsistent body of evidence has associated aspects of suboptimal self‐reported sleep quality with poorer cognitive performance. The current study investigated whether self‐reported sleep quality parameters predict the slope of domain specific cognitive performance.MethodParticipants were drawn from the Australian Imaging, Biomarkers and Lifestyle study of ageing. Linear mixed effect model (LMM) analyses were conducted on 525 cognitively unimpaired, older adults (M = 74.1, SD = 5.5, 56.4% female), characterised by apolipoprotein E (APOE) ε4 status, with baseline self‐reported sleep characteristics. Comprehensive cognitive assessments were conducted over a minimum 3 timepoints (range 29.64 ‐ 98.16 months). All models included random slopes, random intercepts, interaction effects for time, and APOE ε4 carriage, with each model adjusted based on the model of best fit for each cognitive outcome variable of interest.ResultFollowing Bonferroni correction, sleep duration &lt;6 hours and sleep efficiency &lt;65% in the whole cohort, and in APOE ε4 non‐carriers, forecasted accelerated decline in attention and speed of processing. In the same groups, greater sleep efficiency (%) forecasted greater preservation within the attention and speed of processing domain. No associations were observed for other sleep variables or cognitive domains of interest.ConclusionThese findings suggest a role for self‐reported suboptimal sleep efficiency and duration in the early stages of cognitive decline, represented by declining attention and speed of processing performance, in cognitively unimpaired individuals. Additionally, short sleep duration and poor sleep efficiency may increase future risk of cognitive decline independent of APOE ε4 carriage. Our findings also suggest the potential utility of self‐report screening for sleep efficiency and duration as a marker for increased risk of declining attention and speed of processing performance. Individuals with suboptimal sleep may benefit from an intervention to improve sleep efficiency and duration to lessen future risk of cognitive decline.

Fluid Biomarkers of Neurodegeneration in Mild Cognitive Impairment: A Meta‐Analysis

AbstractBackgroundMild cognitive impairment (MCI) is a well‐established prodromal stage of Alzheimer’s disease and is often accompanied by early signs of neurodegeneration (e.g., neuronal loss) that may influence subsequent prognosis. To facilitate a better characterization of the underlying neuropathology, a thorough investigation of proteins associated with neurodegenerative processes in MCI is needed. Thus, the present study systematically assessed the available literature to quantitatively evaluate cerebrospinal fluid (CSF) and peripheral blood concentrations of biomarkers related to neurodegeneration in individuals with MCI compared to healthy controls (HCs).MethodOriginal peer‐reviewed articles that assessed the following CSF and/or peripheral biomarkers: neurofilament light chain (NFL), total‐tau (T‐tau), glial fibrillary acidic protein (GFAP), heart‐type fatty acid binding protein (HFABP), neuron‐specific enolase (NSE), and S100 calcium‐binding protein B (S100B) in both MCI and HCs were included for meta‐analysis. Standardized mean differences (SMDs) and 95% confidence intervals were calculated using a random‐effects model. Heterogeneity was assessed using the I2 statistic.ResultA total of 109 study cohorts were included in the meta‐analysis. In CSF, concentrations of NFL (MCI n = 2771, HC n = 4263, SMD [95% CI] = 0.69 [0.56, 0.83], p &lt; 0.001), GFAP (MCI n = 513, HC n = 1620, SMD [95% CI] = 0.41 [0.08, 0.74], p = 0.02), and HFABP (MCI n = 363, HC n = 245, SMD [95% CI] = 0.57 [0.23, 0.55], p &lt; 0.001) were elevated in MCI. In peripheral blood, concentrations of NFL (MCI n = 6520, HC n = 9439, SMD [95% CI] = 0.41 [0.32, 0.49], p &lt; 0.001), T‐tau (MCI n = 4463, HC n = 5921, SMD [95% CI] = 0.19 [0.09, 0.29], p &lt; 0.001), and GFAP (MCI n = 1758, HC n = 3179, SMD [95% CI] = 0.39 [0.23, 0.55], p &lt; 0.001) were increased in MCI. Significant heterogeneity was identified for all comparisons and was explored through meta regression and subgroup analysis.ConclusionThe present study identified several fluid biomarkers of neurodegeneration in MCI. Importantly, elevated biomarker levels can be detected in both CSF and less‐invasively through peripheral blood. Future studies should focus on assessing the clinical utility of monitoring these biomarkers as they may provide further insight into neuronal and astroglial pathology occurring in the early stages of cognitive decline.

Comparison of sleep and wake EEG biomarkers in mild cognitive impairment and Alzheimer’s disease

AbstractBackgroundEEG slowing, a biomarker of cognitive decline in Alzheimer’s disease (AD), has been reported in wake or sleep EEG [1,2,3]. However, the relation between wake and sleep EEG and their comparative sensitivity to early stage of cognitive decline is less understood. In this study we compared sleep and wake EEG biomarkers using a common set of endpoints.MethodsParticipants included individuals with mild cognitive impairment (MCI, n = 30, ages 53‐88), Alzheimer’s disease dementia (ADem, n = 15, ages 60‐84), and controls with normal cognition (HC, n = 55, ages 50‐84). Twenty‐channel resting‐state EEG with eyes‐closed was collected during 5‐minutes of wakefulness (STAT X24). Sleep EEG recordings from AF7‐AF8 were collected in‐home and staged using Sleep ProfilerTM. Power spectral densities (PSD) and the derived Theta‐Alpha ratios were computed for wake EEG sites (counterpart bipolar montage), with the wake FP1‐FP2 compared by stage to the sleep EEG at AF7‐AF8. Significant differences in Theta‐Alpha ratios between MCI or ADem vs. HC groups were identified using independent t‐test (p&lt;0.05) with the normalized effect size measured using Hedges‐g (E.S.).ResultsCorrelation coefficients between wake Alpha, Theta power and non‐REM sleep were: r = 0.83, 0.75 for stage N1, r = 0.71, 0.66 for stage N2, and r = 0.55, 0.50 for stage N3. Based on the frontal Theta‐Alpha ratios, the ADem group showed significant EEG slowing during both wake (E.S. = 0.73) and sleep (E.S. = 1.65, 1.31, 0.61, 1.71 for N1, N2, N3, and REM) as compared to the HC, while MCI group only exhibited EEG slowing during sleep (E.S. = 0.56, 0.77, 0.51 for N1, N2 and REM). Temporal (T5‐T6) wake EEG manifested significant slowing in both ADem (E.S. = 1.21) and MCI (E.S. = 0.56) groups. Compared to the HC, ADem patients exhibited significantly less sleep time (E.S. = 0.91, p = 0.002) and less stage REM (E.S. = 1.0, p = 0.001).ConclusionsCognitive decline in the AD spectrum is associated with common signatures in both sleep and wake EEG. However, the magnitude of these effects and their spatial distribution may be different in sleep versus wakefulness. These findings support a multi modal approach to neurophysiological assessment using both sleep and wakefulness data.