Subjective Cognitive Decline Research Articles

Construction of physical activity promoting indicators system for older adults with subjective cognitive decline using Delphi method

Construction of physical activity promoting indicators system for older adults with subjective cognitive decline using Delphi method

Functional connectivity changes in two cortico-hippocampal networks of Alzheimer's disease continuum and their correlations with cognition: A SILCODE study.

The anterior-temporal (AT) and posterior-medial (PM) networks have been proposed to play pivotal roles in the memory processing associated with Alzheimer's disease (AD). Nevertheless, these two networks' intrinsic functional coupling characteristics are still vague in different AD stages. To explore the functional connectivity (FC) alterations within and across the AT&PM networks in patients with dementia of the Alzheimer's type (DAT), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and normal controls (NC). A total of 368 participants over 50 years old from the SILCODE study were recruited, including 99 NC, 134 SCD, 67 MCI, and 68 DAT patients. All the participants underwent a resting-state functional magnetic resonance imaging scan and a battery of neuropsychological tests. The 56 regions-of-interest of the AT&PM networks were defined broadly following existing literature. The FCs were calculated using DPABINet and compared among these four groups. Correlation analyses were performed on FCs and cognitive tests. Analysis of variance of all four groups showed significant alteration, mainly in the PM networks. Compared to NC, globally decreased FCs regarding AT&PM networks were observed in DAT and MCI patients, while globally increased FCs regarding AT&PM networks were observed in SCD. The decreased FCs in DAT were significantly correlated with the neuropsychological test on the memory domain. The FC alteration showed different patterns across the AD continuum, especially in individuals with SCD. The elevated FCs in the AT&PM networks of SCD may implicate certain compensating processes in the early stage of AD.

Physical Activity Component of the Greek Interventional Geriatric Study to Prevent Cognitive Impairment and Disability (GINGER): Protocol Development and Feasibility Study

Background/Objectives: Individuals with subjective cognitive decline (SCD) have an increased risk of developing dementia, while non-pharmacological multicomponent lifestyle interventions are recommended for prevention/management. The Greek Interventional Geriatric Initiative to Prevent Cognitive Impairment and Disability (GINGER) is such a multicomponent approach, encompassing simultaneous interventions (cognitive training, depression and sleep management, etc.). Exercise/Physical activity (PA) is suggested as one such intervention. This study (i) presents the exercise protocol developed for GINGER and (ii) explores its feasibility (acceptability, applicability, adherence, users’ satisfaction and reliability). Methods: Exercise/PA protocol development, targeting SCD individuals aged > 55 years, utilized relevant guidelines/literature followed by focus group involving exercise specialists. Data were synthesized through consensus to design optimal exercise interventions prescribed on participant’s physical capacity (heart rate, exertion, etc.), comprising 6-month combined aerobic, strengthening, balance and dual-task exercises, delivered 3 times/weekly in two group-based supervised sessions (in-person and online) and one home-based session. Physical outcomes include balance, aerobic capacity [2-Minute Walk Test (2 MWT), IPAQ-7], strength [Hand Grip Strength (HGS), Sit-to-Stand], fear of falling. Eligibility for entering intervention is low IPAQ-7, 2 MWT or HGS scoring. Feasibility was explored with adherence (exercise diaries and Exercise Adherence Rating Scale) and satisfaction (Patient Satisfaction Questionnaire) Results: Intervention was easily delivered with good reliability across testers’ assessments on 13 SCD participants (ICCs = 0.62–0.99), and improved physical outcomes, whereas users’ adherence and satisfaction scored highly. Conclusions: The exercise protocol for SCD was feasible, acceptable, applicable, reliable, demonstrating adherence and satisfaction, while improving physical parameters. It is thus integrated in the GINGER study, where multiple simultaneous interventions will take place to prevent/enhance cognitive function.

The Contribution of the Face-Name Associative Recognition Test to Objectifying the Impairment of Associative Memory in Subjective Cognitive Decline

Objective: Subjective cognitive decline (SCD) is defined as a self-reported perception of cognitive decline that occurs without clear objective signs of cognitive impairment. There is still uncertainty in the literature about the reliability of SCD as an accurate indicator of the early stages of major neurocognitive disorders. Furthermore, objectifying cognitive impairment in SCD is difficult, mainly due to the insensitivity of the assessment instruments. The main objective of this study was to investigate the potential contribution of the face-name associative recognition test (FNART) to the objective identification of memory impairment in SCD. Method: A research sample of 69 adults with SCD and 69 healthy controls (HCs) recruited in the community were administered in the FNART, which included 32 photographs of neutral faces associated with 32 first names. Results: The total score of the HC group in the FNART was significantly better than that of the SCD group. Moreover, analyses based on the serial position of the stimuli showed that the SCD group performed significantly worse than the HC group only for the middle items (stimuli placed at the beginning or end of learning lists are more likely to be recalled than those presented in the middle), while no primacy and recency effects were found in the HCs. Conclusions: These findings indicate that associative episodic memory is more vulnerable in individuals with subjective cognitive decline (SCD) compared to those without cognitive complaints. Additionally, they suggest that the FNART may be effective in identifying cognitive decline in the preclinical stage of Alzheimer’s disease.

Long COVID and recovery from Long COVID: quality of life impairments and subjective cognitive decline at a median of 2 years after initial infection

BackgroundRecovery from SARS CoV-2 infection is expected within 3 months. Long COVID occurs after SARS-CoV-2 when symptoms are present for more than 3 months that are continuous, relapsing and remitting, or progressive. Better understanding of Long COVID illness trajectories could strengthen patient care and support.MethodsWe characterized functional impairments, quality of life (QoL), and cognition among patients who recovered from SARS-CoV-2 infection within 3 months (without Long COVID), after 3 months (Recovered Long COVID), or remained symptomatic (Long COVID). Among 7305 patients identified with previous SARS-CoV-2 infection between March 2020 and December 2021, confirmed in the medical record with laboratory test or physician diagnosis, 435 (6%) completed a single self-administered survey between March 2022 and September 2022. Multi-domain QoL and cognitive concerns were evaluated using PROMIS-29 and the Cognitive Change Index-12.ResultsNearly half the participants (47.7%) were surveyed more than 2 years from initial infection (median = 23.3 months; IQR = 18.6, 26.7) and 86.7% were surveyed more than 1 year from infection. A significantly greater proportion of the Long COVID (n = 215) group, (Current and Recovered combined), had moderate-to-severe impairment in all health domains assessed compared to those Without Long COVID (n = 220; all p < 0.05). The Recovered Long COVID group (n = 34) had significantly lower prevalence of fatigue, pain, depression, and physical and social function impairment compared to those with Current Long COVID (n = 181; all p < 0.05). However, compared to patients Without Long COVID, the Recovered Long COVID group had greater prevalences of fatigue, pain (p ≤ 0.06) and subjective cognitive decline (61.8% vs 29.1%; p < 0.01). Multivariate relative risk (RR) regression indicated Long COVID risk was greater for older age groups (RR range 1.46–1.52; all p ≤ 0.05), those without a bachelor’s degree (RR = 1.33; 95% CI = 1.03–1.71; p = 0.03), and those with 3 or more comorbidities prior to SARS-CoV-2 infection (RR = 1.45; 95% CI = 1.11–1.90; p < 0.01).ConclusionsLong COVID is associated with long-term subjective cognitive decline and diminished quality of life. Clinically significant cognitive complaints, fatigue, and pain were present even in those who reported they had recovered from Long COVID. These findings have implications for the sustainability of participation in work, education, and social activities.

Introduction and preliminary psychometric evaluation of the assessment of functional capacity interview for older adults

Measures of complex functional decision-making capacity can greatly aid in assessing mild cognitive impairment (MCI) and facilitating early intervention in dementia care. We examined the ability of the Assessment of Functional Capacity Interview (AFCI) to detect functional differences among older adults who were cognitively unimpaired (CU), or who presented with subjective cognitive decline (SCD) or MCI. A sample of 97 older adults (CU; n = 30, Mage = 74.64 ± 7.42 years; SCD; n = 34, Mage = 72.56 ± 6.43 years; MCI; n = 33, Mage = 78.28 ± 7.55 years) underwent neuropsychological testing and responded to the Financial Capacity Instrument (FCI-SF). Informants completed the Assessment of Functional Capacity (AFCI), an instrument of functional decision-making capacity, and responded to the Social Vulnerability Scale (SVS15) and Amsterdam Instrumental Activity of Daily Living (A-IADL-Q-SV), a measure of functional status, for comparison. According to informant-reported responses, the CU group had significantly lower AFCI total (and domain) scores, H(2) = 27.59, p<.001, relative to MCI. Additionally, the CU group had significantly lower AFCI scores in the Home and Personal Safety domain relative to the SCD group, H(2) = 14.06, p<.05. In the overall sample, AFCI total scores were associated with FCI-SF, SVS15, and A-IADL-Q-SV scores and cognitive measures. Our results demonstrate that the AFCI is sensitive to impairment in safety, social, financial, and medical functioning in MCI and is associated with measures of cognitive functioning and social vulnerability in older adults. Incorporating this instrument as a supplement to cognitive screening instruments may aid in the prevention of hazardous decision-making in older adults.

Exploring the Association Between Loneliness, Subjective Cognitive Decline, and Quality of Life Among Older Thai Adults: A Convergent Parallel Mixed-Method Study.

Examining the rising prevalence of subjective cognitive decline as an early indicator of dementia in adults, this study investigates its complex interaction with loneliness and quality of life in individuals with preclinical dementia. Using a convergent parallel mixed-method approach, we employed Structural Equation Modeling on a cohort of 149 older adults. Qualitative insights were derived from focused group discussions and in-depth semi-structured interviews with a cohort of 23 older adults. Loneliness emerges as a pivotal contributor, exerting a discernible partial indirect effect on quality of life through subjective cognitive decline (indirect effect = -0.145, p = .006). Noteworthy differentials surfaced, with the impact of subjective cognitive decline on quality of life heightened in those with chronic diseases (△χ2 = 6.139, p = .013). Loneliness, wielding a palpable impact, intricately interlaces with quality of life, the nexus of which is intricately mediated by subjective cognitive decline.

Association Between Adverse Childhood Experiences and Cognitive Decline

Abstract We aim to study Adverse childhood experiences' (ACEs') association with cognitive decline during adulthood. We reviewed data on subjective cognitive decline (SCD) for those ≥45 years of age. Logistic regression analysis, odds ratio, and 95% confidence interval (CI) assessed the association between ACEs and SCD. We analyzed an adult survey (N = 3900, mean age: 60.9 years, male: 46%). The most common ACE reported was household substance abuse (22.4%), followed by parental divorce/separation (20.9%). The prevalence of SCD in those having at least one ACE was higher than those without any (16.5% vs. 8.1%, p &lt; 0.001). SCD positively correlated with the number of ACEs (p &lt; 0.001). The odds of SCD increase in proportion to the increase in the number of ACEs experienced. These findings should be replicated in a larger population while controlling for confounding factors.

Citrus supplementation in subjective cognitive decline: results of a 36-week, randomized, placebo-controlled trial

BackgroundDeveloping interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD.MethodsEighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis.ResultsThe RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time < .001, d = 0.36, p time x treatment = .910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p < .001) and scales of subjective memory (p < .01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d = 0.69 in short-term, and d = 0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time = .010, d = 0.21, p time x treatment = .772). Adverse events were balanced between groups.ConclusionsIn this randomized clinical trial, long-term Citrus peel extract supplementation did not show cognitive benefits over placebo in participants with SCD, possibly due to high placebo response. These findings might have specific implications for designing future nutraceutical trials in individuals experiencing SCD.Trial registrationThe trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 (https://www.clinicaltrials.gov/ct2/show/NCT04744922).

Perceptual learning and neural correlates of virtual navigation in subjective cognitive decline: A pilot study

Perceptual learning and neural correlates of virtual navigation in subjective cognitive decline: A pilot study

Subjective Cognitive Decline Patterns in Patients with Migraine, with or without Depression, versus Non-depressed Older Adults

Purpose: Cognitive decline is a common complaint in young patients with migraine, especially those with depression. Independent of psychiatric factors such as depression, subjective cognitive decline (SCD) is associated with an elevated risk of progression to dementia. This study aimed to investigate patterns of subjective cognitive complaints between migraineurs with or without depression and non-depressed older adults.Methods: This retrospective study included 331 outpatients with SCD (293 from a headache clinic and 38 from a memory clinic). SCD was diagnosed as “yes” based on two questions about SCD. The Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function. The SCD Questionnaire (SCD-Q) with three subdomains was analyzed to compare SCD between groups.Results: Among patients with SCD, significant differences in duration of education were found among the groups—specifically, migraineurs with depression (12.39 years) had longer education than non-depressed older adults (10.50 years) and shorter education than migraineurs without depression (14.28 years). The total MMSE and MoCA scores did not differ between migraineurs with and without depression. Regarding SCD-Q scores, migraineurs with depression showed higher scores overall and in all cognitive domains than migraineurs without depression, with no significant difference compared to non-depressed older adults. Conclusion: Although the depressed migraineurs with SCD were younger and more educated than the non-depressed older adults with SCD, both groups reported similarly high levels of SCD. Higher levels of surveillance for cognitive decline are warranted for migraineurs with depression who have SCD.

Forecasting cognitive functioning: an artificial intelligence approach with Dynamic Bayesian Networks

Abstract Background Several potentially modifiable risk factors are associated with subjective cognitive decline (SCD). However, developmental patterns of these risk factors have not been used before to forecast later SCD. Practical tools for the prevention of cognitive decline are needed. We examined multifactorial trajectories of risk factors, and their associations with SCD using an artificial intelligence approach to build a score that forecasts later SCD. Methods Five repeated surveys (2000-2022) of the Helsinki Health Study (n = 8960, 79% women, aged 40-60 at Phase 1) were used to build dynamic Bayesian networks (DBN) for estimating the odds of SCD. A score-based approach was implemented for learning DBN using the quotient normalized maximum likelihood criterion. The model was used to predict SCD based on the history of consumption of fruit and vegetables, smoking, alcohol consumption, leisure-time physical activity, body mass index, and insomnia symptoms, adjusting for sociodemographic covariates. Results Of the participants, 31-48% reported decline in memory, learning, and concentration in 2022. Physical activity was the strongest predictor of SCD in a 5-year interval, with an odds ratio of 0.76 (95% Bayesian credible interval 0.59-0.99) for physically active compared to inactive participants. Alcohol consumption showed a U-shaped relationship with SCD. Other risk factors had minor effects. Conclusions A new online risk score tool was developed that enables individuals to inspect their own risk profiles, as well as explore potential targets for interventions and their estimated contributions to later SCD. Dynamic decision heatmap was presented as a communication tool to be used at healthcare consultations. Key messages • Potentially modifiable health-related behaviours such as physical activity can contribute to subjective cognitive decline. • Artificial intelligence can be applied to discover the complex interactions between risk factors and subjective cognitive decline, to support preventive healthcare at individual and population levels.

Cognitive status and demographics modify the association between subjective cognition and amyloid.

This study examined the effect of cognitive status, education, and sex on the association between subjective cognitive decline (SCD) and Alzheimer's disease (AD) biomarkers in non-demented older adults. Vanderbilt Memory and Aging Project participants (n = 129), dementia or stroke free, completed fasting lumbar puncture, SCD assessment, and cognitive assessment. Cerebrospinal fluid (CSF) biomarkers for AD were analyzed. Linear regression models related SCD to CSF AD biomarkers and follow-up models assessed interactions of SCD × cognitive status, sex, reading level, and education on AD biomarkers. In main effect models, higher SCD was associated with more amyloidosis (p-values <0.004). SCD was not associated with tau, p-tau, or neurofilament light (NFL) levels (p-values >0.38). SCD score interacted with cognitive status (p < 0.02), sex (p = 0.03), and education (p-values <0.005) on amyloidosis. In stratified models, higher SCD was associated with more amyloid in cognitively unimpaired (p-values <0.003), men (p = 0.0003), and higher education. No SCD score × reading-level interaction was found (p-values >0.51) though SCD related to amyloid markers in the higher reading-level group (p-values <0.004). Higher SCD was associated with greater cerebral amyloid accumulation, one of the earliest pathological AD changes. SCD appears most useful in detecting early AD-related brain changes prior to objective cognitive impairment, in men, and those with higher quantity and quality of education and highlight the importance of considering these factors.

Association Between Dietary Diversity and Subjective Cognitive Decline in the Middle-Aged and Elderly Chinese Population: A Cross-Sectional Study.

This cross-sectional study aimed to examine the association between dietary diversity and risk of subjective cognitive decline (SCD), a precursor of dementia, in middle-aged and elderly Chinese populations residing in eastern China. Participants aged ≥ 45 years were recruited from a community in an eastern Chinese city after excluding potential objective cognitive impairment using the Mini-Cognitive Assessment Instrument (Mini-Cog). SCD was assessed using the Subjective Cognitive Decline Questionnaire-9 (SCD-Q9). Dietary data were collected using the Dietary Quality Questionnaire (DQQ), and the Food Group Diversity Score (FGDS) and the Consumed All Five Recommended Food Score (All-5) were calculated as indicators of dietary diversity. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to evaluate the associations of FGDS and All-5 scores with SCD after adjusting for age, sex, socioeconomic status, lifestyle factors, and health status. Among the 871 participants, 358 (41.1%) were classified as having SCD. Compared with participants with the highest FGDS (≥8) and those with the highest All-5 score (5), those with the lowest FGDS (≤4) and the lowest All-5 score (≤3) exhibited 85% (OR = 1.85; 95% CI: 1.10-3.13; p = 0.02) and 90% (OR = 1.90; 95% CI: 1.21-2.97; p < 0.01) higher risk of SCD, respectively, after adjusting for all covariates. Fruits were the only food group among the All-5 components that demonstrated a significant association with SCD risk. Poor dietary diversity was associated with an elevated risk of SCD in middle-aged and older adults, and fruits were the food group with the most substantial effect.

Unveiling the hippocampal subfield changes across the Alzheimer's disease continuum: a systematic review of neuroimaging studies.

Studies exploring the hippocampal subfield atrophy in Alzheimer's disease (AD) have shown contradictory results. This review aims to disentangle such heterogeneity by investigating the dynamic changes of hippocampal subfields across the AD continuum. We systematically searched the PubMed and EMBASE databases for case-control studies. Selected studies included investigations of biomarker-based amyloid status and reported data on hippocampal subfield atrophy using advanced MRI techniques. Twelve studies were included. Despite high heterogeneity, a distinguishable pattern of vulnerability of hippocampal subfields can be recognized from the cognitively unimpaired phase to the dementia stage, shedding light on hippocampal changes with disease progression. Consistent findings revealed atrophy in the subiculum and presubiculum, along with a potential increase in volume in the cornu ammonis (CA) among the cognitively unimpaired group, a feature not observed in patients experiencing subjective cognitive decline. Atrophy in the subiculum, presubiculum, CA 1-4, and the dentate gyrus characterized the mild cognitive impairment stage, with a more pronounced severity in the progression to dementia.

Association of Neurogranin and BACE1 With Clinical Cognitive Decline in Individuals With Subjective Cognitive Decline.

CSF biomarkers have immense diagnostic and prognostic potential for Alzheimer disease (AD). However, AD is still diagnosed relatively late in the disease process, sometimes even years after the initial manifestation of cognitive symptoms. Thus, further identification of biomarkers is required to detect related pathology in the preclinical stage and predict cognitive decline. Our study aimed to assess the association of neurogranin and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) with cognitive decline in individuals with subjective cognitive decline (SCD). We enrolled participants with available neurogranin and BACE1 measurements in CSF from the DELCODE (DZNE-Longitudinal Cognitive Impairment and Dementia, Germany) cohort. The longitudinal change of Preclinical Alzheimer's Cognitive Composite score was assessed as the primary outcome in participants with SCD and controls. The secondary outcome was defined as conversion of SCD to mild cognitive impairment (MCI) during follow-up. Levels of neurogranin, BACE1, and neurogranin/BACE1 ratio across groups were compared by analysis of covariance after adjustment for demographics. The linear mixed-effects model and Cox regression analysis were applied to evaluate their association with cognitive decline and progression of SCD to MCI, respectively. A total of 530 participants (mean age: 70.76 ± 6.01 years, 48.7% female) were analyzed in the study. The rate of cognitive decline was faster in individuals with SCD with higher neurogranin and neurogranin/BACE1 ratio (β = -0.138, SE = 0.065, p = 0.037, and β = -0.293, SE = 0.115, p = 0.013). Higher baseline neurogranin and neurogranin/BACE1 ratio were associated with an increased rate of conversion from SCD to MCI (hazard ratio [HR] 1.35 per SD, 95% CI 1.03-1.77, p = 0.028, and HR 1.53 per SD, 95% CI 1.13-2.07, p = 0.007). In addition, the impact of higher neurogranin levels on accelerating the rate of cognitive decline was more pronounced in the SCD group than in cognitively unimpaired controls (β = -0.077, SE = 0.033, p = 0.020). Our findings suggest that CSF neurogranin and BACE1 begin to change in the preclinical stage of AD and they are associated with clinical progression in individuals with SCD.

Plasma neurofilament light chain as prognostic marker of cognitive decline in neurodegenerative diseases, a clinical setting study.

Analysis of selected research cohorts has highlighted an association between plasma neurofilament light (NfL) protein and cross-sectional cognitive impairment as well as longitudinal cognitive decline. However, the findings have yielded inconsistent results regarding its possible application in clinical practice. Despite its potential prognostic significance, the role of plasma NfL in daily clinical practice with unselected patients suffering from cognitive impairment remains largely unexplored. This retrospective, cross-sectional and longitudinal monocentric study enrolled 320 patients with Alzheimer's disease ([AD], n = 158), dementia with Lewy body ([DLB], n = 30), frontotemporal dementia ([FTD], n = 32), non-neurodegenerative diseases ([NND], n = 59) or subjective cognitive decline ([SCD], n = 41). Plasma NfL levels were measured at baseline on the Simoa platform. AD, DLB, and FTD patients were also analyzed altogether as a 'degenerative conditions' subgroup, whereas SCD and NND were grouped as a 'non-degenerative conditions' subgroup. We assessed the relationship between plasma NfL levels and cross-sectional cognitive performance, including global cognition and six specific cognitive domains. A subset of 239 patients had follow-up mini-mental state examinations (MMSE) up to 60 months. Models were adjusted on age, education level, glomerular filtration rate and body mass index. In 320 patients, baseline plasma NfL levels were negatively associated with global cognition (β=-1.28 (-1.81 ; -0.75) P < 0.001), memory (β=-1.48 (-2.38 ; -0.59), P = 0.001), language (β=-1.72(-2.49 ; -0.95) P < 0.001), praxis (β=-2.02 (-2.91 ; -1.13) P < 0.001) and executive functions (β=-0.81, P < 0.001). Across diagnosis, plasma NfL levels were negatively associated with cross-sectional global cognition in all but the SCD subgroup, specifically with executive functions and memory in AD (respectively β=-0.71(-1.21 ; -0.211), P = 0.005 and β=-1.29 (-2.17 ; -0.42), P = 0.004), and with attention in LBD (β=-0.81(-1.16 ; -0.002), P = 0.03). Linear mixed-effects models showed that plasma NfL predicted MMSE decline in the global population (βPlasmaNfLxTime=-0.15 (-0.26 ; -0.04), P = 0.006), as in the neurodegenerative condition subgroup (βPlasmaNfLxTime=-0.21 (-0.37 ; - 0.06), P = 0.007), but not in non-neurodegenerative condition subgroup. In our clinical cohort, plasma NfL was associated with faster cognitive decline in neurodegenerative dementia, which corroborates data obtained in research cohorts. Yet, plasma NfL was not predictive of accelerated cognitive decline in individuals without neurodegeneration, suggesting its use as a neurodegeneration-specific predictive biomarker.

Associations between accelerated forgetting, amyloid deposition and brain atrophy in older adults.

Accelerated long-term forgetting (ALF) is the phenomenon whereby material is retained normally over short intervals (e.g. minutes) but forgotten abnormally rapidly over longer periods (days or weeks). ALF may be an early marker of cognitive decline, but little is known about its relationships with preclinical Alzheimer's disease pathology, and how memory selectivity may influence which material is forgotten. We assessed ALF in 'Insight 46', a sub-study of the MRC National Survey of Health and Development (a population-based cohort born during one week in 1946) (n=429; 47% female; assessed aged ∼73 years). ALF assessment comprised visual and verbal memory tests: Complex Figure Drawing and the Face-Name Associative Memory Exam (FNAME). ALF scores were calculated as the percentage of material retained after 7 days, relative to 30 minutes. In 306 cognitively-normal participants, we investigated effects on ALF of β-amyloid pathology (quantified using 18F-Florbetapir-PET, classified as positive/negative) and whole-brain and hippocampal atrophy rate (quantified from serial T1-MRI over ∼2.4 years preceding the ALF assessment), as well as interactions between these pathologies. We categorized Complex Figure Drawing items as 'outline' or 'detail', to test our hypothesis that forgetting the outline of the structure would be more sensitive to the effect of brain pathologies. We also investigated associations between ALF and Subjective Cognitive Decline, measured with the MyCog questionnaire. Complex Figure 'outline' items were better retained than 'detail' items (mean retention over 7 days = 94% vs 72%). Amyloid-positive participants showed greater forgetting of the Complex Figure outline, compared to amyloid-negatives (90% vs 95%; P<0.01). There were interactions between amyloid pathology and cerebral atrophy, such that whole-brain and hippocampal atrophy predicted greater ALF on Complex Figure Drawing among amyloid-positives only (e.g. 1.9 percentage-points lower retention per ml/year of whole-brain atrophy [95% confidence intervals 0.5, 3.7]; P<0.05). Greater ALF on FNAME was associated with increased rate of hippocampal atrophy. ALF on Complex Figure Drawing also correlated with subjective cognitive decline (-0.45 percentage-points per MyCog point [-0.85, -0.05], P<0.05). These results provide evidence of associations between some measures of ALF and biomarkers of brain pathologies and subjective cognitive decline in cognitively-normal older adults. On Complex Figure Drawing, 'outline' items were better remembered than 'detail' items - illustrating the strategic role of memory selectivity - but 'outline' items were also relatively more vulnerable to ALF in individuals with amyloid pathology. Overall, our findings suggest that ALF may be a sensitive marker of cognitive changes in preclinical Alzheimer's disease.

Neurophysiological markers of early cognitive decline in older adults: a mini-review of electroencephalography studies for precursors of dementia.

The early detection of cognitive decline in older adults is crucial for preventing dementia. This mini-review focuses on electroencephalography (EEG) markers of early dementia-related precursors, including subjective cognitive decline, subjective memory complaints, and cognitive frailty. We present recent findings from EEG analyses identifying high dementia risk in older adults, with an emphasis on conditions that precede mild cognitive impairment. We also cover event-related potentials, quantitative EEG markers, microstate analysis, and functional connectivity approaches. Moreover, we discuss the potential of these neurophysiological markers for the early detection of cognitive decline as well as their correlations with related biomarkers. The integration of EEG data with advanced artificial intelligence technologies also shows promise for predicting the trajectory of cognitive decline in neurodegenerative disorders. Although challenges remain in its standardization and clinical application, EEG-based approaches offer non-invasive, cost-effective methods for identifying individuals at risk of dementia, which may enable earlier interventions and personalized treatment strategies.

Factors influencing physical activity behavior in older adults with subjective cognitive decline: an empirical study using SEM and fsQCA methods.

Despite the evident potential benefits of engaging in physical activity (PA) for older adults with subjective cognitive decline (SCD), their PA levels remains low. Previous research has predominantly focused on PA behaviors in individuals with dementia/mild cognitive impairment, with limited attention given to those with SCD. Therefore, this study aims to identify key factors influencing PA behavior in older adults with SCD based on the Self-Determination Theory (SDT) and the capability-opportunity-motivation (COM-B) model. Three hundred and three individuals aged 60 and above with SCD participated in this study. A face-to-face structured questionnaire survey was conducted. Data were analyzed using Structural Equation Modeling (SEM) and Fuzzy Set Qualitative Comparative Analysis (fsQCA). SEM results indicate that PA social support primarily influences PA behavior through three indirect pathways: the separate mediating effect of basic psychological needs, the separate mediating effect of motivation, and the chained mediating effect of both. Physical literacy, on the other hand, influences PA behavior through the separate mediating effect of motivation. Necessary conditions analysis by fsQCA reveals that no single factor is necessary for promoting PA behavior in older adults with SCD, while sufficiency analysis identifies four different combinations of factors leading to PA behavior. The model derived from the framework of SDT and the COM-B model effectively explains and predicts the interrelationships among variables. Physical activity behavior in older individuals with SCD is the result of multifactorial synergies.