Subjective Memory Complaints Research Articles

Transformers for autonomous recognition of psychiatric dysfunction via raw and imbalanced EEG signals

Early identification of mental disorders, based on subjective interviews, is extremely challenging in the clinical setting. There is a growing interest in developing automated screening tools for potential mental health problems based on biological markers. Here, we demonstrate the feasibility of an AI-powered diagnosis of different mental disorders using EEG data. Specifically, this work aims to classify different mental disorders in the following ecological context accurately: (1) using raw EEG data, (2) collected during rest, (3) during both eye open, and eye closed conditions, (4) at short 2-min duration, (5) on participants with different psychiatric conditions, (6) with some overlapping symptoms, and (7) with strongly imbalanced classes. To tackle this challenge, we designed and optimized a transformer-based architecture, where class imbalance is addressed through focal loss and class weight balancing. Using the recently released TDBRAIN dataset (n= 1274 participants), our method classifies each participant as either a neurotypical or suffering from major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), subjective memory complaints (SMC), or obsessive–compulsive disorder (OCD). We evaluate the performance of the proposed architecture on both the window-level and the patient-level. The classification of the 2-min raw EEG data into five classes achieved a window-level accuracy of 63.2% and 65.8% for open and closed eye conditions, respectively. When the classification is limited to three main classes (MDD, ADHD, SMC), window level accuracy improved to 75.1% and 69.9% for eye open and eye closed conditions, respectively. Our work paves the way for developing novel AI-based methods for accurately diagnosing mental disorders using raw resting-state EEG data.

Subjective Cognitive Decline and Frailty Trajectories and Influencing Factors in Japanese Community-Dwelling Older Adults: A Longitudinal Study.

We studied frailty and subjective cognitive decline (SCD) trajectories in older Japanese adults and evaluated the influence of various factors on these trajectories. We analyzed data from 1157 non-demented adults aged 70 and above from 2013 to 2019. Frailty was assessed using the self-administered Kihon Checklist (KCL), a Japanese frailty index. SCD was evaluated using the questionnaire of the Subjective Memory Complaints scale. Through group-based joint trajectory models, we discerned three frailty trajectories: non-progressive (n = 775), moderate progressive (n = 312), and rapid progressive (n = 70); and three SCD trajectories: non-progressive (n = 302), moderate progressive (n = 625), and rapid progressive (n = 230). Individuals in the rapid progressive SCD trajectory had a 32.2% probability of also being in the rapid progressive frailty trajectory. In contrast, those in the non-progressive SCD trajectory had zero probability of being in the rapid progressive frailty trajectory. Both the rapid progressive frailty and SCD groups combined had a higher incidence of depressive symptoms and slow gait speed. Our results have found that frailty and SCD share a similar trajectory in Japanese older adults. Additionally, rapid progressive frailty and SCD were associated with the highest risk of depressive symptoms and slow gait speed. Thus, interventions targeting both frailty and cognitive decline should prioritize mental health enhancement and gait speed improvement.

Longitudinal relationships between grip strength, subjective memory complaints and cognitive function among middle-aged and older adults in China.

Subjective memory complaints are considered an early sign of cognitive decline. Recent evidence shows that grip strength is an important predictor of cognitive function. However, few studies have compared whether one condition is uniquely associated with cognitive function when another condition is controlled for. To explore the longitudinal associations of cognitive function with subjective memory complaints and grip strength in middle-aged and older adults, with a particular focus on whether one condition is uniquely associated with cognitive function when another condition is considered. A total of 3,877 middle-aged and older adults (aged 45-92years) from the China Health and Retirement Longitudinal Study reported on their demographic and health status and completed measures of grip strength and subjective memory complaints, as well as a series of cognitive tests, every two years between 2011 and 2015. Generalized estimating equation models were used to assess the relationships between grip strength, subjective memory complaints, and cognitive function. Grip strength was longitudinally associated with cognitive function (β = 0.021, 95% confidence interval [CI]: 0.011, 0.030, P < 0.001) independent of subjective memory complaints. In contrast, changes in the subjective memory complaints were not related to cognitive function over time (β = 0.107, 95% CI: - 0.025, 0.238, P = 0.112). Only at baseline subjective memory complaints were associated with poorer cognitive function (β = - 1.142, 95% CI: - 1.309, - 0.975, P < 0.001). Grip strength might be a more important clinical correlate of cognitive function decline over time than subjective memory complaints. Regular assessment and close monitoring of grip strength might help identify individuals who might be at high risk for cognitive impairment.

Heterogeneity in Measures and Rates of Reported Dementia and Subjective Memory Complaints Across U.S. National Surveys.

Several U.S. health surveillance surveys contain items related to self- and proxy reports of dementia and subjective memory complaints (SMC). Despite their similar content, these items differ in terminology, item specificity, and time frame. The goal of this study was to analyze whether item features might influence endorsement rates for dementia and SMC. We calculated design-appropriate estimates for the endorsement of dementia and SMC across U.S.-based national surveys and employed pairwise comparisons to evaluate endorsement rates across surveys. We also examined item characteristics to explore possible effects on endorsement rates. Endorsement rates were wide-ranging for dementia (ranging from 2.7% to 9.9%) and SMC (5.6% to 46.6%). Pairwise comparisons revealed statistically significant differences on most dementia-related items (76%), and all SMC comparisons (100%). Items varied substantially in the terminology used to assess dementia and SMC (e.g., "dementia" vs "Alzheimer's disease") and used different time frames (e.g., "past month" vs "5 years"). National survey data on reported dementia and SMC can have important research, training, and policy implications, yet endorsement rates vary widely across surveys. That variability could emerge from subtle but influential item characteristics, and our findings highlight the need for item harmonization, in even their most basic characteristics. Standardizing items across national surveillance surveys facilitates comparison across surveys so that we can better understand the true burden of these conditions to inform public health initiatives.

The relationship between APOE genotype, CSF Tau and cognition across the Alzheimer's disease spectrum, moderation and mediation role of insula network connectivity.

To investigate whether insula network connectivity modulates the relationship between apolipoprotein E (APOE) ε4 genotype, cerebrospinal fluid (CSF) biomarkers (Aβ, Tau, and pTau) and cognition across Alzheimer's disease (AD) spectrum. Forty-six cognitive normal (CN), 35 subjective memory complaint (SMC), 41 mild cognitive impairment (MCI), and 32 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were obtained. Multivariable linear regression analyses were conducted to investigate the main effects and interaction of the APOE genotype and disease status on the insula functional connectivity (IFC) network. Mediation and moderation analysis were performed to investigate whether IFC strengths regulate the association between APOE genotype, CSF biomarkers and cognition. Additionally, the support vector machine (SVM) model integrating APOE genotype, CSF biomarkers, and neuroimaging biomarkers (insula volumes and altered regional IFCs) was used to classify the AD spectrum. The interactive effect of the APOE genotype and disease on the insula network was found in the left medial superior frontal gyrus (SFGmed.L), right anterior medial prefrontal cortex (aMPFC.R), and bilateral thalamus (THA.B). The functional connectivities (FCs) in the left insula (LIns) connecting with the left posterior middle temporal gyrus (pMTG.L), SFGmed.L, and right lingual gyrus (LING.R) were correlated with cognition. LIns-SFGmed.L and LIns-pMTG.L FCs could moderate the effects of Tau on cognition. Furthermore, LIns-SFGmed.L FC may suppress the association between APOE genotype and cognition. More importantly, the integrated biomarkers from the SVM model yielded strong powers for classifying the AD spectrum. Insula functional connectivity regulated the association between APOE genotype, CSF Tau and cognition and provided stage-dependent biomarkers for early differentiation of the AD spectrum. The present study used a cross-sectional design. Follow-up studies are needed to validate the relationship.

Food insecurity and subjective cognitive complaints among adults aged ≥ 65 years from low- and middle-income countries

PurposeTo date, no study has investigated the association between food insecurity and subjective cognitive complaints (SCC). Thus, the aims of the present study were to examine this association among older adults in low- and middle-income countries (LMICs), and to identify the potential mediators in this association, given the importance of SCC in dementia risk among older people, and the projected particularly large increase in dementia in this setting.MethodsCross-sectional, community-based, nationally representative data from the World Health Organization (WHO) Study on global AGEing and Adult Health (SAGE) collected between 2007 and 2010 were analyzed. Two questions on subjective memory and learning complaints in the past 30 days were used to create a SCC scale ranging from 0 (No SCC) to 100 (worse SCC). Past 12 month food insecurity was assessed with two questions on frequency of eating less and hunger due to lack of food. Multivariable linear regression and mediation (Karlson–Holm–Breen method) analyses were conducted to assess associations.ResultsData on 14,585 individuals aged ≥ 65 years [mean (SD) age 72.6 (11.5) years; 55.0% females] were analyzed. Severe food insecurity (vs. no food insecurity) was associated with 9.16 (95% CI = 6.95–11.37) points higher mean SCC score. Sleep/energy (mediated% 37.9%; P < 0.001), perceived stress (37.2%; P = 0.001), and depression (13.7%; P = 0.008) partially explained the association between severe food insecurity and SCC.ConclusionFood insecurity was associated with SCC among older adults in LMICs. Future studies should assess whether addressing food insecurity among older adults in LMICs can improve cognitive health.

Effects of human probiotics on memory and psychological and physical measures in community-dwelling older adults with normal and mildly impaired cognition: results of a bi-center, double-blind, randomized, and placebo-controlled clinical trial (CleverAge biota).

This study presents results of our randomized clinical trial studying the effect of human probiotics on memory and psychological and physical measures following our study protocol registered at clinicaltrials.gov NCT05051501 and described in detail in our previous paper. Community dwelling participants aged between 55 and 80 years were randomly assigned to receive a single dose of 106 colony-forming units of human Streptococcus thermophilus GH, Streptococcus salivarius GH NEXARS, Lactobacilus plantarum GH, and Pediococcus pentosaceus GH or placebo. A cross-over design allowed each group to receive probiotics and placebo for 3 months each in reverse order. A small subset of participants was examined online due to the COVID-19 pandemic. After 6 months a small number of volunteers were additionally assessed after 2 months without any intervention. Primary outcome measures included changes in cognitive functions assessed using brief tests and a neuropsychological battery and changes in mood assessed using validated questionnaires. Secondary outcome measures included changes in self-report and subjective measures using depression and anxiety questionnaires, seven visual analog scales of subjective feelings (memory, digestion, etc.), and physical performance. At baseline, the probiotic-placebo group A (n = 40, age 69 ± 7 years, education 16 ± 3 years, 63% females, body mass index 28.5 ± 6, subjective memory complaint in 43%) did not differ from the placebo-probiotic group B (n = 32) in any of the sociodemographic characteristics and evaluated measures including cognitive status. At follow-up visits after 3, 6, and 8 months, no cross-sectional differences in any of the measures were found between the groups except worse sentence recall of the ALBA test after 3 months of probiotic use. Score changes were not observed for all cognitive tests but one in any group between visits 1 and 3 and between visits 3 and 6. The only change was observed for the TMT B test after the first three months but no change was observed after the second three months. The treatment with human probiotics and prebiotics did not improve cognitive, affective, or physical measures in community-dwelling individuals with normal or mildly impaired cognitive functions. clinicaltrials.gov, identifier NCT05051501.

Subjective Memory Complaints Predict Decline in Memory, Instrumental Activities of Daily Living, and Social Participation in Older Adults: A Fixed-Effects Model.

Although subjective memory complaints (SMCs) have been suggested to be associated with future memory impairment, limitations in instrumental activities of daily living (IADLs), and social participation restriction, these associations are still inconclusive. To determine whether changes in SMCs over time predict decline in memory, IADLs, and social participation in older adults. Longitudinal study. Community. Sample 1 included 2,493 community-dwelling older adults drawn from the Health and Retirement Study (HRS) data collected between 2004 and 2018. Sample 2 included 1,644 community-dwelling older adults drawn from the HRS data collected between 2008 and 2018. Self-reported SMCs, memory function, self-reported IADL performance, and self-reported social participation. The mean age of Sample 1 at baseline was 70.16 yr; 1,468 (58.88%) were female. In Sample 1, immediate and delayed memory (all ps < .001) and IADL performance (p < .01) declined over time. Increases in SMCs over time significantly predicted future immediate and delayed memory declines (p < .01 and p < .001, respectively) and future IADL performance decline (p < .001), after controlling for depressive symptoms. The mean age of Sample 2 at baseline was 71.52 yr; 928 (56.45%) were female. In Sample 2, social participation declined over time (all ps < .001). Increases in SMCs over time significantly predicted future social participation decline (p < .05), after controlling for depressive symptoms. Increases in SMCs predict future decline in memory, IADL performance, and social participation after accounting for depressive symptoms. What This Article Adds: SMCs can be used as an early indicator of future memory impairment, IADL limitations, and social participation restrictions in older adults. Furthermore, interventions that minimize SMCs may help older adults achieve successful aging.

Functional Cognitive Disorder and Mild Cognitive Impairment: A Thin Line

AimsFunctional cognitive disorders (FCDs) refer to conditions where patients present with persistent problematic subjective memory complaints that are not consistent with their observed level of cognitive functioning. The demonstrated symptoms are also not in keeping with a recognized psychiatric or neurodegenerative process. FCD is likely to be underdiagnosed in clinical practice with the place-holder label of mild cognitive impairment being used in some cases due to lack of clarity about its symptomatology. In this paper, we describe two cases whose presentations were suggestive of FCDs.MethodsMrs X, 53 years old female not previously known to mental health services referred for increasing difficulties with her memory over 2 years which she believed was impacting her activities of daily living. She has a history of ischaemic heart disease, fibromyalgia, Insulin-dependent diabetes mellitus, depression, and polycystic ovarian syndrome. On assessment MOCA = 15/30, and MMSE = 25/30.Mr Y, 57 years old male not known to mental health services. Although, has been treated for anxiety and depression by GP. He presented with a 3-year history of struggling with his memory. He reported being forgetful of appointments and he has to paste sticky papers on the fridge for reminders. Similarly, he has a diagnosis of Fibromyalgia and essential hypertension. On Assessment MOCA – 19/30 and MMSE – 25/30.ResultsFCDs can be quite challenging because the clinical picture overlaps with other neurodegenerative conditions. Typically, patients report issues around memory function in the absence of relevant neuropathology and with evidence of inconsistency between symptoms reported and observations at assessment. Regarding our cases, the primary presenting issues were increasing difficulties with memory, and forgetfulness. Other noteworthy observations were a mismatch between their scores in the MOCA, MMSE, their level of functioning, and reported memory problems. Neurological examinations and neuroimaging were not suggestive of any neurodegenerative disorders. A differential diagnosis of functional cognitive disorder was considered due to the discrepancies between symptoms reported, the level of their functioning, observations at assessments as well as absence of relevant neuropathology on imaging.ConclusionFCD is a condition that is common in clinical practice but underdiagnosed. Hence, it is imperative that clinicians keep this diagnosis in mind when patients present with memory difficulties that do not meet the diagnostic criteria for dementia and is not due to a recognized medical or psychiatric condition. Correctly identifying and diagnosing FCD can positively impact patient outcomes.

Hippocampal volume in cases of relapsing remitting multiple sclerosis and its correlation with cognitive impairment

Background. Multiple sclerosis (MS) is a chronic inflammatory immune-mediated disease, distinguished by demyelination and oligodendropathy in the central nervous system. Cognitive impairment (CI) can impact patients at any stage of MS, including those with clinically isolated syndrome (CIS). Patients and methods. This is a prospective cross-sectional study which enrolled 60 patients with RRMS. They were subjected to cognitive scale assessment, routine brain MRI study and volumetric assessment of hippocampus. Results. This study found a significant positive correlation between duration of disease and Subjective memory complaints questionnaire (r=0.525, p=0.001). A significant negative correlation existed between disease duration and MMSE score (r=-0.404, p=0.001) and between disease duration and MoCA score (r=-0.310, p=0.016). No significant difference between both groups regarding the relative hippocampal volume. Mean relative right hippocampal volume is 0.0026 for cases versus 0.0027 among control group and mean relative left hippocampal volume is 0.0025 for cases versus 0.0026 among control group. Conclusion. Multiple sclerosis disease duration had an impact on cognitive state. However, hippocampal volume assessment did not predict the cognitive affection in patient with RRMS.

A Pilot Study of Adjunctive Group Therapy to Enhance Coping With Cognitive Challenges and Support Cognitive Health After Electroconvulsive Therapy.

Concerns about the cognitive adverse effects of electroconvulsive therapy (ECT) are common among recipients of the treatment despite its relatively small adverse effects on cognitive functioning. Interventions aimed at remediating or improving coping with cognitive adverse effects of ECT have not been developed. The Enhancing Cognitive Domains after ECT (ENCODE) program is a new group intervention aimed at teaching self-management strategies to cope with the cognitive challenges and associated anxiety that often accompanies ECT. This pilot study used a pretest-posttest design to examine the feasibility and clinical utility of delivering ENCODE to 20 adults who had received ECT in a hospital-based ECT program. The program was found to be both feasible and acceptable as indicated by the attainment of recruitment targets, high rates of attendance (85% of participants attended at least 5 of the 6 group sessions), and high participant satisfaction ratings (88% reported that ENCODE helped or helped very much to manage their cognitive challenges). The clinical utility of the program was suggested by reductions in depressive symptom severity and subjective memory complaints. Nonsignificant improvements were observed in global cognitive function and cognitive self-efficacy. This study provides preliminary evidence for the feasibility and clinical utility of ENCODE based on program demand, strong participant satisfaction, and postgroup reductions in distress and subjective memory complaints.

Development and testing of an intervention to increase staff knowledge and confidence in responding to health anxiety in the context of cognitive decline: a pilot study.

Memory complaint in the absence of organic pathology is a common phenomenon accounting for up to one third of patients presenting to memory clinics. Health anxiety has been specifically linked to dementia worry and repeated presentations to the National Health Service (NHS). Providing reassurance that an individual does not have dementia appears ineffective in reducing presentations to primary and secondary care services. This study sought to evaluate and establish the effectiveness of a 1-hour pilot training workshop to enhance healthcare professionals' knowledge and confidence to those with health anxiety around cognitive decline. The one-session pilot training workshop was developed and informed by previous work and consultation with the 2Gether NHS Foundation Trust Memory Assessment Service staff. The training workshop was then evaluated by employing an idiosyncratic self-report questionnaire. Participants completed the questionnaire prior to and after the training workshop. Pre- and post-training questionnaires revealed that the pilot training workshop was effective in increasing perceived knowledge and confidence in staff responding to patients presenting with health anxiety and co-occurring subjective memory complaints. The findings suggest that healthcare professionals may benefit from training in identifying and addressing health-anxious individuals with subjective memory complaints. This may have implications in the provision of psychologically informed care offered in a memory assessment service. Recommendations are made for further enhancing the effectiveness of staff training and promoting alternative service treatment pathways.

Development of a Revised Version of Subjective Memory Complaints Questionnaire in Taiwan: A Preliminary Study.

Research has suggested that subjective memory complaints (SMC) are predictive of cognitive decline in cases of Alzheimer's disease; however, multidimensional characteristics of SMC make it difficult to formulate causal links. The Subjective Memory Complaints Questionnaire (SMCQ) has proven effective in capturing the nature of SMC. In this study, we developed a revised version of SMCQ (SMCQ-R) with corresponding normative data for application in Taiwan. This study recruited 100 cognitively normal participants (> 45years) stratified according to demographic characteristics. Assessments were performed to evaluate test-retest reliability, criterion-related validity, and construct validity of SMCQ-R. SMCQ-R scores of 20 matched patients with mild cognitive impairment (MCI) were also compared with those of normal participants to test construct validity. Reliability of SMCQ-R was satisfactory (0.81-0.95). Factor analysis revealed a three-factor structure: everyday memory problems (EMP), recent severe memory problems (RSMP), and long-term memory problems (LTMP). EMP and RSMP scores were negatively associated with objective cognitive function (r = -.20 to .39). Depressive symptoms were positively associated with all factors (r = .23-.33). Age was positively associated with total (b = 0.09, p < .05) and EMP scores (b = 0.06, p < .01). MCI patients obtained higher scores (p < .05) on all subscales. SMCQ-R scores discriminated between normal and MCI individuals (area under the curve = 0.77). This study established a norm based on scores adjusted to control for effects of age. SMCQ-R has sound psychometric properties and could potentially be used as a tool to assess SMC in clinical settings.

Can a failure in the error-monitoring system explain unawareness of memory deficits in Alzheimer’s disease?

Unawareness of memory deficits is an early manifestation in patients with Alzheimer’s disease (AD), which often delays diagnosis. This intriguing behavior constitutes a form of anosognosia, whose neural mechanisms remain largely unknown. We hypothesized that anosognosia may depend on a critical synaptic failure in the error-monitoring system, which would prevent AD patients from being aware of their own memory impairment. To investigate, we measured event-related potentials (ERPs) evoked by erroneous responses during a word memory recognition task in two groups of amyloid positive individuals with only subjective memory complaints at study entry: those who progressed to AD within the five-year study period (PROG group), and those who remained cognitively normal (CTRL group). A significant reduction in the amplitude of the positivity error (Pe), an ERP related to error awareness, was observed in the PROG group at the time of AD diagnosis (vs study entry) in intra-group analysis, as well as when compared with the CTRL group in inter-group analysis, based on the last EEG acquisition for all subjects. Importantly, at the time of AD diagnosis, the PROG group exhibited clinical signs of anosognosia, overestimating their cognitive abilities, as evidenced by the discrepancy scores obtained from caregiver/informant vs participant reports on the cognitive subscale of the Healthy Aging Brain Care Monitor. To our knowledge, this is the first study to reveal the emergence of a failure in the error-monitoring system during a word memory recognition task at the early stages of AD. This finding, along with the decline of awareness for cognitive impairment observed in the PROG group, strongly suggests that a synaptic dysfunction in the error-monitoring system may be the critical neural mechanism at the origin of unawareness of deficits in AD.

Neurophenotypes of COVID-19: Risk factors and recovery outcomes

Coronavirus disease 2019 (COVID-19) infection is associated with risk of persistent neurocognitive and neuropsychiatric complications. It is unclear whether the neuropsychological manifestations of COVID-19 present as a uniform syndrome or as distinct neurophenotypes with differing risk factors and recovery outcomes. We examined post-acute neuropsychological profiles following SARS-CoV-2 infection in 205 patients recruited from inpatient and outpatient populations, using an unsupervised machine learning cluster analysis, with objective and subjective measures as input features. This resulted in three distinct post-COVID clusters. In the largest cluster (69%), cognitive functions were within normal limits, although mild subjective attention and memory complaints were reported. Vaccination was associated with membership in this “normal cognition” phenotype. Cognitive impairment was present in the remaining 31% of the sample but clustered into two differentially impaired groups. In 16% of participants, memory deficits, slowed processing speed, and fatigue were predominant. Risk factors for membership in the “memory-speed impaired” neurophenotype included anosmia and more severe COVID-19 infection. In the remaining 15% of participants, executive dysfunction was predominant. Risk factors for membership in this milder “dysexecutive” neurophenotype included disease-nonspecific factors such as neighborhood deprivation and obesity. Recovery outcomes at 6-month follow-up differed across neurophenotypes, with the normal cognition group showing improvement in verbal memory and psychomotor speed, the dysexecutive group showing improvement in cognitive flexibility, and the memory-speed impaired group showing no objective improvement and relatively worse functional outcomes compared to the other two clusters. These results indicate that there are multiple post-acute neurophenotypes of COVID-19, with different etiological pathways and recovery outcomes. This information may inform phenotype-specific approaches to treatment.

Endogenous hormones in mid‐life and later‐life subjective memory impairment in women

AbstractBackgroundReproductive hormones may impact cognition in women. Recent literature suggests that subjective memory complaints (SMCs) can be an early indicator of cognitive impairment. However, epidemiologic data are mixed, with few prospective studies exploring endogenous sex hormones in relation to later‐life SMCs. Assessing this potential association may elucidate an etiology of risk for cognitive impairment in women.MethodWe included 616 premenopausal and 102 postmenopausal women from the New York University Women’s Health Study (NYUWHS), a prospective cohort study with blood samples collected at enrollment (1985‐91) and over 35 years of follow‐up to collect health and lifestyle information. Women were ineligible for inclusion in the cohort if they used hormone medications or were pregnant 6 months prior to enrollment. Healthy controls from prior NYUWHS case‐control studies were eligible for participation in this study if their baseline blood sample had already been used to measure circulating hormones, and they responded to at least one of two follow‐up questionnaires (2018‐present) featuring 6 questions about SMCs. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of baseline hormones with subsequent SMCs, adjusting for age, race, education, original case‐control study, and body mass index (BMI) in a separate model.ResultAndrostenedione, testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone binding globulin (SHBG) were measured in samples collected at baseline for pre‐ and post‐menopausal women; estradiol and estrone were also measured in postmenopausal women. There were no significant associations between premenopausal circulating hormones or SHBG and SMCs. Postmenopausal hormones were inversely associated with SMCs, including in age and BMI‐adjusted models: ORs (95% CIs) for SMCs associated with doubling in testosterone and estradiol were 0.58 (0.35‐0.95) and 0.39 (0.17‐0.90), respectively.ConclusionHigher postmenopausal concentrations of testosterone and estradiol are inversely associated with risk of later‐life SMCs in women.

The intrinsic locus coeruleus functional connectivity change in older adults with subjective memory complaint

AbstractBackgroundThe locus coeruleus (LC) is critical for late‐lift cognitive processing by modulating the norepinephrine system, which is often the first place Alzheimer’s pathology appears. Previous researches have identified that the LC was associated with late‐life cognitive ability. This study aims to investigate whether the intrinsic LC functional connectivity (LC‐FC) is altered in older adults with subjective memory complaints (SMC).MethodA total of 199 participants were selected from the Alzheimer’s Disease Neuroimaging Initiative database, including 95 SMC older adults and 104 cognitively normal individuals (CN). Bilateral LCs were selected to construct the LC functional connectivity based on resting‐state fMRI data. The cognitive function was evaluated by using the ADNI composite executive function (ADNI‐EF) and memory (ADNI‐Mem) scores at baseline and 24 months later. Data were analyzed using the voxel‐wise two‐sample t‐test and partial correlation analysis, we utilized permutation testing with threshold‐free cluster enhancement (TFCE) to multiple comparison correction.ResultThere were no significant differences in demographic information and cognitive function between the two groups. In the left LC‐FC network, compared to CN group, the SMC group showed increased LC‐FC in the left salient network (anterior insula, and frontal operculum cortex), hippocampus, and right default mode network(DMN, inferior temporal gyrus), while they had decreased LC‐FC in left inferior temporal gyrus. No significant difference in the right LC‐FC network between the two groups. The altered FC between left LC and right inferior temporal gyrus (DMN) was significantly associated with ADNI‐EF performance in the SMC group, controlled the effect of age, gender, and APOE genotype (r = ‐0.404, p = 0.002), and the FC between LC and right ITG was also associated with executive function performance after 24 months in SMC group.ConclusionThe present study manifested the abnormal intrinsic LC functional connectivity in elder adults with SMC. In addition, the FC between LC and default mode network was associated with the executive function performance in SMC. These findings might suggest an LC norepinephrine system compensatory mechanism in cognitive processing in older individuals with SMC.

Subjective memory complaints, white matter hyperintensities, and cognitive decline in a population‐based cohort study

AbstractBackgroundSubjective memory complaints (SMCs) are associated with a faster cognitive decline and dementia; whether this relationship results from irreversible structural brain alterations, such as white matter hyperintensities (WMH), requires investigation. We aimed to determine the association of SMCs with WMH and cognitive decline and investigate the role of WMH on the relationship between SMCs and cognitive decline.MethodWe studied 917 participants (63% African Americans and 60% women) from the population‐based Chicago Health and Aging Project (CHAP), who responded to questions about SMCs, underwent magnetic resonance imaging of the brain, and had valid cognitive data on two or more visits during the follow‐up period. SMCs were obtained by self‐report questionnaire, and based on frequency and severity of concerns, we categorized participants into three groups: not concerned, moderately concerned, and very concerned.ResultOf 917 participants eligible for the study, 158 (17.2%) had no SMCs concerns, 671 (73.2%) had moderate concerns, and 88 (9.6%) were very concerned. SMCs were associated with larger WMH volumes and faster cognitive decline. Compared to participants with no concerns, those very concerned had 0.833 (95%CI 0.203, 1.463) units higher WMH volumes and 174% faster cognitive decline (‐0.049; 95%CI ‐0.076, ‐0.022). The association between SMCs and cognitive decline was statistically significant only among individuals with large WMH volumes; that is, very concerned individuals with large WMH volumes had 428% faster cognitive decline annually (‐0.077; 95%CI ‐0.144, ‐0.011) than participants with no concerns. In participants with low volumes of WMH, SMCs were not associated with a faster cognitive decline (P‐value = 0.595).ConclusionOur study suggests that SMCs, frequently reported by the elderly, are an important sign of cognitive impairment, especially in people with brain atrophies, such as large WMH volumes.

Longitudinal trajectories of self‐reported subjective cognitive decline in relation to objective cognitive performance in a population‐based cohort

AbstractBackgroundSubjective Cognitive Decline (SCD) may represent the onset of cognitive decline before impairment on standard cognitive tests occurs (Jessen et al., 2014). Previous cross‐sectional studies were shown to have limited ability to capture objective differences in cognitive performance between groups with and without SCD (Cacciamani et al., 2017). Understanding the interplay between changes in subjective memory ratings and objective cognitive function over time may have utility in identifying people at risk of dementia.Method370 cognitively normal (CN) individuals with complete cognitive data (Table 1 for characteristics) from Insight 46, a longitudinal neuroscience sub‐study of the MRC National Survey for Health and Development (the British 1946 Birth Cohort), underwent cognitive, clinical, and physical assessments, and neuroimaging (combined MRI/18F‐Florbetapir‐PET). SCD was measured using MyCog (Rami et al., 2014) a validated tool, from the SCD‐Questionnaire, where higher scores indicate greater subjective complaints. Linear regression models were used to test whether longitudinal cognitive change as measured using the Preclinical Alzheimer Cognitive Composite (PACC) and a visual short‐term memory binding task were influenced by baseline MyCog and whether there are parallel associations between rates of change in MyCog and longitudinal cognitive change. Covariates were sex, age at baseline visit, childhood cognitive ability, educational attainment, and adult socioeconomic position.ResultBaseline MyCog scores did not predict rates of change in PACC or visual short‐term memory binding outcome measures (Table 2). Rates of MyCog change alone did not predict rate of change in PACC, localisation error, total correct number of trials or proportion of misbinding errors (Table 3). However, we observed an interaction effect with baseline amyloid‐b status, whereby greater rates of subjective memory concerns predicted faster rates of decline in the proportion of misbinding errors in amyloid‐b positive participants only (Table 3; Figure 1).ConclusionThese findings suggest that higher amyloid‐b burden in CN individuals with subjective memory complaints is associated with faster rates of decline in visual working memory. Corroborating previous reports that feature binding tasks can objectify subtle cognitive deficits found in SCD (Koppara et al., 2015) and serve as a promising tool for identifying people at risk of dementia.

Quantifying AD‐related brain amyloid with linearised progression models: Model‐based vs. data‐based

AbstractBackgroundBrain amyloid‐β (Aβ) is the pathological hallmark of Alzheimer’s disease (AD). In logistic disease models, Aβ accumulation is a sigmoid function of time‐since‐disease‐onset (TSDO) (figure 1). Previous positron emission tomography (PET)‐based models vary accumulation onset(t50) and duration(r) globally; capacity(K) and baseline(NS) regionally (Whittington2018). We confirm existing approaches and propose a more powerful ICA‐based approach to quantify disease severity and estimate TSDO.MethodWe used 1071 18F‐florbetapir standard uptake value ratio (SUVR) images from the ADNI‐2 study (adni.loni.usc.edu/data‐samples/data‐types/pet). Images were mapped into MNI space. Averages were extracted using the Harvard‐Oxford brain‐atlas. Whole‐brain tracer‐specific sigmoid parameters (Jack2013) obtained from the literature were used to estimate TSDO.Of 16 models of regional Aβ accumulation (each of the 4 regional sigmoid parameters varied either regionally or globally), the optimal Bayesian information criterion was found with global t50 and r, and regional NS and K (figure 1) with global values r = 6.16y and t50 = 4.10y.Linearised maps of NS and K were obtained by regressing the SUVR maps onto the global sigmoid. We also estimated these maps as independent components, using a 2‐component ICA on the SUVR maps. Both outcomes were used to quantify Aβ accumulation from SUVR images as weighting factors of the accumulation map.We compared the weights from the logistic model and the ICA model in ADNI, using effect size measured with Hedges' g between cognitively normal (CN), subjective memory complaints (SMC), mild cognitive impairment (EMCI/MCI/LMCI) and AD groups. We compared 3 longitudinal visits (N = 112) in the OASIS‐3 study (see www.oasis‐brains.org) with both methods, global SUVR and Centiloid (Klunk2015) using 11C‐PiB PET SUVR images.ResultMaps of accumulation capacity from both models had spatial correlation of 0.86 (figure 2); baseline maps had spatial correlation of 0.95. Hedges' g between ADNI groups was 2.25 for K, and 2.42 for ICA (1.46 for global SUVR). In OASIS‐3, Hedges' g between visits was 1.24 for K, 1.46 for ICA (global SUVR 0.15, Centiloid 0.4).ConclusionWe demonstrate that linear accumulation models can be used to quantify brain Aβ with PET; maps obtained by ICA yield larger effect sizes than the logistic method for differentiating groups and measuring changes between visits.