Subjective Cognitive Decline Research Articles

The relationship between dementia caregivers and quality of life in South Korean populations.

The purpose of this study was to assess the relationship between quality of life and dementia caregivers. The 2019 Korean Community Health Survey participants were assessed using the Patient Health Questionnaire-9, subjective cognitive decline (SCD) and SCD-related functional limitation, and EuroQol 5-dimension (EQ-5D). Sociodemographic and psychosocial variables were evaluated and compared between participants with dementia caregivers (n = 37,614) and non-dementia caregivers (n = 140,518). The dementia caregivers group reported significantly higher rates of depression, SCD, SCD-related functional restriction, and mean EQ-5D compared to the non-dementia caregivers group (P < .001). After adjusting for multiple confoundings, the odds ratio (OR) for depression (Patient Health Questionnaire-9 ≥ 10), SCD, SCD-related functional limitation, and lowest quartile of the EQ-5D index scores in the dementia caregivers group were 1.43 (95% confidence interval [CI], 1.29-1.59), 1.30 (95% CI: 1.24-1.36), 1.26 (95% CI: 1.20-1.32), and 1.22 (95% CI: 1.16-1.29), respectively. Physical activity (OR: 1.47; 95% CI: 1.43-1.52), self-control (OR: 1.41; 95% CI: 1.35-1.47), daily activity (OR: 1.55; 95% CI: 1.50-1.60), pain (OR: 1.62; 95% CI: 1.58-1.67), and anxiety/depression (OR: 2.17; 95% CI: 2.10-2.24) were all more common among participants in the dementia caregivers group than in the non-dementia family caregivers group. Depression, SCD, and a lower quality of life are linked to dementia caregivers, especially if there is moderate to severe anxiety or depression.

Relationship Between Excessive Daytime Sleepiness and Caudate Nucleus Volume in Patients with Subjective Cognitive Decline: A Study from the SILCODE Using the Volbrain.

Excessive daytime sleepiness (EDS) and caudate nucleus volume alterations have been linked to Alzheimer's disease (AD), but their relationship remains unclear under the context of subjective cognitive decline (SCD). This study aimed to investigate the relationship between EDS and caudate nucleus volume in patients with SCD. The volume of entire brain was measured in 170 patients with SCD, including 37 patients with EDS and 133 non-EDS, from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Participants underwent a comprehensive assessment battery, including neuropsychological and clinical evaluations, blood tests, genetic analysis for APOE ɛ4, and structural MRI scans analyzed using the fully automated segmentation tool, volBrain. Patients with EDS had significantly increased volume in the total and left caudate nucleus compared to non-EDS. The most significant cognitive behavioral factor associated with caudate nucleus volume in the EDS was the Auditory Verbal Learning Test-recognition. These findings suggest that EDS may be associated with alterations in caudate nucleus volume, particularly in the left hemisphere, in the context of SCD. Further research is necessary to understand the underlying mechanisms of this relationship and its implications for clinical management.

Global left frontal cortex connectivity attenuates the adverse effect of brain atrophy on global cognition in non-dementia participants

Aim: To investigate whether higher global left frontal cortex (gLFC) connectivity, a potential neural substrate of cognitive reserve (CR), mitigates the impact of brain atrophy on cognition in non-dementia participants. Methods: A total of 43 clinically diagnostic normal controls (NC), 63 subjective cognitive decline (SCD) and 30 mild cognitive impairment (MCI) were recruited, who underwent resting-state fMRI and structural MRI scans. The gLFC connectivity was defined as the average positive functional connectivity between the left frontal cortex and each voxel in the gray matter. Hippocampus, parahippocampal gyrus, and amygdala volume volumes/intracranial volume ratio (HpVR, PhgVR, and AmyVR) values were computed as measures of brain atrophy. In general linear analysis, interaction term gLFC connectivity × brain atrophy on global cognition performance were tested, which were repeated in women and men separately. The Trial registration number is NCT03370744. Results: Significant interaction effects of HpVR * gLFC connectivity (P = 0.031) and PhgVR * gLFC connectivity (P = 0.006) were observed, while AmyVR * gLFC connectivity (P = 0.088) showed a marginal significance. After accounting for APOE ε4 carrying status or diagnosis based on amyloidosis, the significant results still existed. In separate analysis, the significant interaction effects of HpVR * gLFC connectivity (P = 0.004), PhgVR * gLFC connectivity (P = 0.017), and AmyVR * gLFC connectivity (P = 0.027) were only observed in men, not in women. Conclusion: The gLFC connectivity is associated with greater resilience against the adverse effect of specified brain atrophy on global cognition, which is more effective in men.

Accurate identification of individuals with subjective cognitive decline using 3D regional fractal dimensions on structural magnetic resonance imaging

Background and ObjectiveAccurate identification of individuals with subjective cognitive decline (SCD) is crucial for early intervention and prevention of neurodegenerative diseases. Fractal dimensionality (FD) has emerged as a robust and replicable measure, surpassing traditional geometric metrics, in characterizing the intricate fractal geometrical properties of brain structure. Nevertheless, the effectiveness of FD in identifying individuals with SCD remains largely unclear. A 3D regional FD method can be suggested to characterize and quantify the spatial complexity of the precise gray matter, providing insights into cognitive aging and aiding in the automated identification of individuals with SCD. MethodsThis study introduces a novel integer ratio based 3D box-counting fractal analysis (IRBCFA) to quantify regional fractal dimensions (FDs) in structural magnetic resonance imaging (MRI) data. The innovative method overcomes limitations of conventional box-counting techniques by accommodating arbitrary box sizes, thereby enhancing the precision of FD estimation in small, yet neurologically significant, brain regions. ResultsThe application of IRBCFA to two publicly available datasets, OASIS-3 and ADNI, consisting of 520 and 180 subjects, respectively. The method identified discriminative regions of interest (ROIs) predominantly within the limbic system, fronto-parietal region, occipito-temporal region, and basal ganglia-thalamus region. These ROIs exhibited significant correlations with cognitive functions, including executive functioning, memory, social cognition, and sensory perception, suggesting their potential as neuroimaging markers for SCD. The identification model trained on these ROIs demonstrated exceptional performance achieving over 93 % accuracy on the discovery dataset and exceeding 87 % on the independent testing dataset. Furthermore, an exchange experiment between datasets revealed a substantial overlap in discriminative ROIs, highlighting the robustness of our method across diverse populations. ConclusionOur findings indicate that IRBCFA can serve as a valuable tool for quantifying the spatial complexity of gray matter, providing insights into cognitive aging and aiding in the automated identification of individuals with SCD. The demonstrated generalizability and robustness of this method position it as a promising tool for neurodegenerative disease research and offer potential for clinical applications.

Characteristics of the White Matter Structural Network in Individuals with Subjective Cognitive Decline with and without APOEε4 Based on Graph Theory Study.

To determine whether individuals with subjective cognitive decline (SCD) have changes in whole-brain network characteristics and intracerebral node characteristics in the structural network, and whether there is a difference between SCD with and without Apolipoprotein E4 (APOEε4). This cross-sectional study included 36 individuals without SCD without APOEε4 (healthy control, HC group), 21 individuals with SCD with APOEε4 (APOEε4+ group), and 33 individuals with SCD without APOEε4 (APOEε4- group). The white matter structural network was constructed using the fractional anisotropy (FA) based deterministic fiber tracking method. Graph theory was used to analyze the whole-brain network characteristics and intracerebral node characteristics of the three groups. Regarding the whole-brain network characteristics, all three groups exhibited small-worldness in their structural networks. The clustering coefficient (Cp) and local efficiency (Eloc) in the APOEε4+ and APOEε4- groups were significantly lower than in the HC group (p < 0.05), but no significant difference in Cp or Eloc was observed between the APOEε4+ and APOEε4- groups. Regarding intracerebral node characteristics, there were significant differences in some brain regions, mainly the default mode network (DMN), the occipital lobe, the temporal lobe, and subcortical regions. The change in intracerebral node characteristics was different between the APOEε4+ group and the APOEε4- group. Individuals with SCD demonstrate changes in whole-brain network characteristics and intracerebral node characteristics in the structural network. Moreover, differences exist between APOEε4+ and APOEε4- individuals.

Mild behavioral impairment domains are longitudinally associated with pTAU and metabolic biomarkers in dementia-free older adults.

The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein and few data on other metabolic markers. We aimed to evaluate the longitudinal association of the MBI domains and a spectrum of plasma biomarkers. Our study is a secondary analysis of data from NOLAN. The longitudinal association of the MBI domains with plasma biomarkers, including pTau181, was tested using adjusted linear mixed-effects models. The sample comprised 359 participants (60% female, mean age: 78.3, standard deviation: 0.3 years). After 1 year, the MBI domain of abnormal perception was associated with steeper increases in plasma pTau181. Abnormal perception, decreased motivation, and impulse dyscontrol were associated with homocysteine or insulin dysregulation. Apart from the association with plasma pTau181, our results suggest that MBI might also represent metabolic dysregulation, probably contributing to dementia transition among older adults with subjective cognitive decline or mild cognitive impairment. Mild behavioral impairment (MBI) psychosis was associated with steeper increases in plasma p. pTau could be a pharmacological target to treat agitation and psychosis symptoms. MBI domains were linked to metabolic dysregulation involving insulin and homocysteine.

Brain age as a biomarker for pathological versus healthy ageing – a REMEMBER study

ObjectivesThis study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions.MethodsThe REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict ‘brain age’ and ‘brain predicted age difference’ (BPAD = brain age–chronological age) for every subject.ResultsMCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p < .001) and BPAD (r = -0.26,p < .001). Noticeable trends, but no significant correlations, were found between BPAD and incidence of conversion from MCI to ADD, nor between BPAD and conversion time from MCI to ADD. BPAD was increased in heavy alcohol drinkers compared to non-/sporadic (p = .014) and moderate (p = .040) drinkers.ConclusionsBrain age and associated BPAD have the potential to serve as indicators for, and to evaluate the impact of lifestyle modifications or interventions on, brain health.

Individual and additive-effect relationships of menopausal symptoms and subjective cognitive decline among nurses during menopausal transition: a cross-sectional study.

This study aimed to examine the individual and additive-effect relationships between menopausal symptoms and subjective cognitive decline among nurses during menopausal transition. Between February and September 2019, a convenience sampling strategy was used, involving 1,335 Chinese nurses undergoing menopausal transition. A general information survey that included the Subjective Cognitive Decline Scale and the Menopause Rating Scale was completed. Based on a cut-off point of the subjective cognitive decline score of 7.5, the overall sample was divided into mild and severe groups. Propensity score matching was performed to balance covariates of mild and severe subjective cognitive decline. The individual and cumulative effects of menopausal symptoms and subjective cognitive decline were analyzed using binary logistic regression and the Cochran-Armitage trend test, respectively. After propensity score matching, none of the parameters showed significant differences between the groups. Logistic regression analysis revealed that four menopausal symptoms were closely associated with severe subjective cognitive decline. The Cochran-Armitage trend test indicated odds ratios linking the presence of these symptoms with increased severe subjective cognitive impairment. In addition, nurses simultaneously experiencing two or more core menopausal symptoms were over six times more likely to have severe subjective cognitive decline than nurses experiencing none or one core menopausal symptom during menopausal transition. Individual and additive numbers of menopausal symptoms significantly influenced subjective cognitive decline in nurses during their menopausal transition. These findings suggest that interventions aimed at enhancing the cognitive performance of nurses experiencing menopause should consider menopausal symptoms.

Age-specific risk factors of depression among the oldest-old - evidence from the multicenter AgeCoDe-AgeQualiDe study.

The present study aimed to investigate age-group-specific incidence rates and risk factors for depressive symptoms in the highest age groups. Data were derived from a prospective multicenter cohort study conducted in primary care - the AgeCoDe/AgeQualiDe study. In total, 2,436 patients 75 years and older were followed from baseline to ninth follow-up. To assess depressive symptoms, the short version of the Geriatric Depression Scale (GDS-15, cutoff score 6) was used. Age-specific competing risk regressions were performed to analyze risk factors for incident depressive symptoms in different age groups (75 to 79, 80 to 84, 85+ years), taking into account the accumulated mortality. The age-specific incidence rate of depression was 33 (95% CI 29-38), 46 (95% CI 40-52) and 63 (95% CI 45-87) per 1,000 person years for the initial age groups 75 to 79, 80 to 84 and 85+ years, respectively. In competing risk regression models, female sex, mobility as well as vision impairment, and subjective cognitive decline (SCD) were found to be risk factors for incident depression for age group 75 to 79, female sex, single/separated marital status, mobility as well as hearing impairment, and SCD for age group 80 to 84, and mobility impairment for age group 85+. Depressive symptoms in latest life are common and the incidence increases with increasing age. Modifiable and differing risk factors across the highest age groups open up the possibility of specifically tailored prevention concepts.

Gardening and subjective cognitive decline: a cross-sectional study and mediation analyses of 136,748 adults aged 45+ years

BackgroundGiven the benefits of gardening for physical and psychological health, we explored whether gardening was associated with lower risks of subjective cognitive decline (SCD), a precursor of dementia, and SCD-related functional limitations.MethodsIncluded in this cross-sectional study were 136,748 participants aged 45 + years old from the Behavioral Risk Factor Surveillance System 2019 survey, who were then categorized into three groups according to self-reported exercise status: non-exercisers, gardeners, and other exercisers. SCD was assessed via a questionnaire, and SCD-related functional limitations were referred to as having difficulties in engaging in household or social activities due to SCD. The odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the associations of gardening with SCD and SCD-related functional limitations, adjusted for age, sex, socioeconomic status, lifestyle factors, and health status. Mediation analyses were conducted to examine whether the observed association between gardening and SCD was mediated by energy expenditure (MET-hours/week), depression status, and consumption of fruits and vegetables.ResultsOverall, 11.1% and 5.4% of participants self-reported experiencing SCD and SCD-related functional limitations, respectively. The adjusted OR for gardeners vs. non-exercisers, was 0.72 (95% CI 0.62–0.83) for SCD and 0.57 (95% CI 0.44–0.73) for SCD-related functional limitations. The observed association between gardening and SCD was explained by higher energy expenditure (39.0%), lower likelihood of having depression (21.5%), and higher consumption of fruits and vegetables (3.4%) (P<0.05 for all). Similar patterns were observed for SCD-related functional limitations.ConclusionIn this nationally representative sample, gardening was associated with better cognitive status, which may be mainly attributed to better depression status and energy expenditure.

Effects of 6-Month Combined Physical Exercise and Cognitive Training on Neuropsychological and Neurophysiological Function in Older Adults with Subjective Cognitive Decline: A Randomized Controlled Trial.

Multidomain intervention may delay or ameliorate cognitive decline in older adults at risk of Alzheimer's disease, particularly in the memory and inhibitory functions. However, no study systematically investigates the changes of brain function in cognitively-normal elderly with subjective cognitive decline (SCD) when they receive multidomain intervention. We aimed to examine whether a multidomain intervention could improve neuropsychological function and neurophysiological activities related to memory and inhibitory function in SCD subjects. Eight clusters with a total of 50 community-dwelling SCD older adults were single-blind, randomized into intervention group, which received physical and cognitive training, or control group, which received treatment as usual. For the neuropsychological function, a composite Z score from six cognitive tests was calculated and compared between two groups. For the neurophysiological activities, event-related potentials (ERPs) of memory function, including mismatch negativity (MMN) and memory-P3, as well as ERPs of inhibitory function, including sensory gating (SG) and inhibition-P3, were measured. Assessments were performed at baseline (T1), end of the intervention (T2), and 6 months after T2 (T3). For the neuropsychological function, the effect was not observed after the intervention. For the neurophysiological activities, improved MMN responses of ΔT2-T1 were observed in the intervention group versus the control group. The multidomain intervention produced a sustained effect on memory-P3 latencies of ΔT3-T1. However, there were no significant differences in changes of SG and inhibition-P3 between intervention and control groups. While not impactful on neuropsychological function, multidomain intervention enhances specific neurophysiological activities associated with memory function.

The Network Structure of Cognitive Impairment: From Subjective Cognitive Decline to Alzheimer's Disease.

It was proposed that a reorganization of the relationships between cognitive functions occurs in dementia, a vision that surpasses the idea of a mere decline of specific domains. The complexity of cognitive structure, as assessed by neuropsychological tests, can be captured by exploratory graph analysis (EGA). EGA was applied to the neuropsychological assessment of people (humans) with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD; total N = 638). Both sexes were included. In AD, memory scores detach from the other cognitive functions, and memory subdomains reduce their reciprocal relation. SCD showed a pattern of segregated neuropsychological domains, and MCI showed a noisy and less stable pattern. Results suggest that AD drives a reorganization of cognitive functions toward a less-fractionated architecture compared with preclinical conditions. Cognitive functions show a reorganization that goes beyond the performance decline. Results also have clinical implications in test interpretations and usage.

Subjective Aging and Basic Activities of Daily Living: Moderation by Health Care Access and Mediation by Health Care Resources.

Subjective aging in older adults is associated with a decline in basic activities of daily living (bADL), although this is less well studied with increasing age cohorts by their healthcare resources (HCR) and healthcare access (HCA) controlling for sociodemographics. We aimed to address this gap in knowledge by analyzing the National Health and Aging Trends round 11 data set on 3303 older adults aged 70 to above 90, comprising 42% male and 58% female by age cohort (middle-old -70-79, n = 1409; older-old -80-89, n = 1432, oldest-old- 90 plus, n = 462). Results of mediation-moderation analysis show the subjective aging whole model comprising subjective cognitive decline, HCR, HCA, and sociodemographic to predict a decline in bADL with increasing age to be higher among the older-old age (80-89) compared to the middle-old age (70-79) or oldest-old (90 years +) cohorts. These findings suggest a "doughnut" effect by which the older-old age cohort of 80-89 may be coping less well with their bADL, while the oldest-old may have adapted to functional loss in their everyday living and/or comprises adults who may have passed a mortality selection despite a more significant burden of comorbidity.

Allostatic load measures in older adults with subjective cognitive decline and mild cognitive impairment: A cross-sectional analysis from the Brazilian Memory and Aging Study

IntroductionAn increasing body of research suggests that stress and allostatic load are related to cognitive dysfunction and neurodegeneration. Objectivesto determine the relationship between allostatic load (AL) and cognitive status in older adults classified with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). MethodologyUsing the Brazilian Memory and Aging Study (BRAMS) database, we analyzed data from 57 older adults with SCD and MCI. Blood neuroendocrine (cortisol, DHEA-s), inflammatory (C-reactive protein, fibrinogen), metabolic (HbA1c, HDL-cholesterol, total cholesterol, creatinine), and cardiovascular (blood pressure, waist/hip ratio) were transformed into an AL index. ResultsDespite a significant difference in the univariate analysis between waist/hip ratio (0.94 in the MCI group vs. 0, 88 in the SCD group, p = 0.03), total cholesterol levels (194 vs. 160, p = 0.02), and AL index (36.9 % in the MCI group vs. 27.2 % in the SCD group, p = 0.04), AL was not associated with SCD or MCI in the multivariate analysis. ConclusionOur data suggest that different profiles of AL in MCI compared to individuals with SCD could be due to cofounding factors. These findings need to be confirmed in longitudinal studies investigating profiles of AL changes at preclinical and prodromal stages of Alzheimer’s disease.

Understanding the Role of Self-Attention in a Transformer Model for the Discrimination of SCD From MCI Using Resting-State EEG.

The identification of EEG biomarkers to discriminate Subjective Cognitive Decline (SCD) from Mild Cognitive Impairment (MCI) conditions is a complex task which requires great clinical effort and expertise. We exploit the self-attention component of the Transformer architecture to obtain physiological explanations of the model's decisions in the discrimination of 56 SCD and 45 MCI patients using resting-state EEG. Specifically, an interpretability workflow leveraging attention scores and time-frequency analysis of EEG epochs through Continuous Wavelet Transform is proposed. In the classification framework, models are trained and validated with 5-fold cross-validation and evaluated on a test set obtained by selecting 20% of the total subjects. Ablation studies and hyperparameter tuning tests are conducted to identify the optimal model configuration. Results show that the best performing model, which achieves acceptable results both on epochs' and patients' classification, is capable of finding specific EEG patterns that highlight changes in the brain activity between the two conditions. We demonstrate the potential of attention weights as tools to guide experts in understanding which disease-relevant EEG features could be discriminative of SCD and MCI.

Sex Differences in the Severity and Progression of Neuropsychiatric Symptoms Across Different Dementia Types.

Dementia presents not only differing neuropsychiatric symptoms (NPS) across Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB) but also subjective cognitive decline (SCD). This study examined sex-based variations in NPS severity and progression across these conditions. We performed a longitudinal cohort study including 1,068 participants. Hierarchical generalized linear mixed models were used to model NPS as a function of disease severity and biological sex at birth. Female participants with AD exhibited NPS more frequently than male participants. In FTD, female participants had more frequent delusions, hallucinations, and depression/dysphoria, while male participants had higher instances of agitation/aggression, apathy, disinhibition, and irritability/lability. In DLB, male participants showed higher instances of depression, and female participants more frequently experienced anxiety. In SCD, female participants showed higher nighttime behaviors. The trajectory of NPS significantly differed between sexes. These findings highlight sex-specific NPS impact in different neurodegenerative conditions.

Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer

Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.

Awareness of episodic memory and meta-cognitive profiles: associations with cerebrospinal fluid biomarkers at the preclinical stage of the Alzheimer's continuum.

The lack of cognitive awareness, anosognosia, is a clinical deficit in Alzheimer's disease (AD) dementia. However, an increased awareness of cognitive function, hypernosognosia, may serve as a marker in the preclinical stage. Subjective cognitive decline (SCD) might correspond to the initial symptom in the dynamic trajectory of awareness, but SCD might be absent along with low awareness of actual cognitive performance in the preclinical stage. We hypothesized that distinct meta-cognitive profiles, both hypernosognosia and anosognosia, might be identified in preclinical-AD. This research evaluated the association between cerebrospinal fluid (CSF) AD biomarkers and the awareness of episodic memory, further exploring dyadic (participant-partner) SCD reports, in the preclinical Alzheimer's continuum. We analyzed 314 cognitively unimpaired (CU) middle-aged individuals (mean age: 60, SD: 4) from the ALFA+ cohort study. Episodic memory was evaluated with the delayed recall from the Memory Binding Test (MBT). Awareness of episodic memory, meta-memory, was defined as the normalized discrepancy between objective and subjective performance. SCD was defined using self-report, and dyadic SCD profiles incorporated the study partner's report using parallel SCD-Questionnaires. The relationship between CSF Aβ42/40 and CSF p-tau181 with meta-memory was evaluated with multivariable regression models. The role of SCD and the dyadic contingency was explored with the corresponding stratified analysis. CSF Aβ42/40 was non-linearly associated with meta-memory, showing an increased awareness up to Aβ-positivity and a decreased awareness beyond this threshold. In the non-SCD subset, the non-linear association between CSF Aβ42/40 and meta-memory persisted. In the SCD subset, higher Aβ-pathology was linearly associated with increased awareness. Individuals presenting only study partner's SCD, defined as unaware decliners, exhibited higher levels of CSF p-tau181 correlated with lower meta-memory performance. These results suggested that distinct meta-cognitive profiles can be identified in preclinical-AD. While most individuals might experience an increased awareness associated with the entrance in the AD continuum, hypernosognosia, some might be already losing insight and stepping into the anosognosic trajectory. This research reinforced that an early anosognosic profile, although at increased risk of AD-related decline, might be currently overlooked considering actual diagnostic criteria, and therefore its medical attention delayed.

A multimodal machine learning model for predicting dementia conversion in Alzheimer’s disease

Alzheimer’s disease (AD) accounts for 60–70% of the population with dementia. Mild cognitive impairment (MCI) is a diagnostic entity defined as an intermediate stage between subjective cognitive decline and dementia, and about 10–15% of people annually convert to AD. We aimed to investigate the most robust model and modality combination by combining multi-modality image features based on demographic characteristics in six machine learning models. A total of 196 subjects were enrolled from four hospitals and the Alzheimer’s Disease Neuroimaging Initiative dataset. During the four-year follow-up period, 47 (24%) patients progressed from MCI to AD. Volumes of the regions of interest, white matter hyperintensity, and regional Standardized Uptake Value Ratio (SUVR) were analyzed using T1, T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRIs, and amyloid PET (αPET), along with automatically provided hippocampal occupancy scores (HOC) and Fazekas scales. As a result of testing the robustness of the model, the GBM model was the most stable, and in modality combination, model performance was further improved in the absence of T2-FLAIR image features. Our study predicts the probability of AD conversion in MCI patients, which is expected to be useful information for clinician’s early diagnosis and treatment plan design.

Understanding Health Beliefs and Health Behaviors in Older Adults at Risk for Alzheimer's Disease.

There are significant public health benefits to delaying the onset of Alzheimer's disease (AD) in individuals at risk. However, adherence to brain healthy behaviors is low. The Health Belief Model proposes that specific beliefs are mediators of behavior change. To characterize health belief measures from the Science of Behavior Change Research Network (SBCRN) in an older adult population and associations between health beliefs, AD risk, and current health behaviors. A total of 172 individuals from the Rhode Island AD Prevention Registry participated. SBCRN health belief measures included assessments of future time perspective, self-efficacy, deferment of gratification, and consideration of future consequences. Outcome measures included individual AD risk index score, dementia risk awareness, and lifestyle behaviors including physical, cognitive, and social activity. Participants who were older had higher scores for AD risk, lower future time perspective, and lower generalized self-efficacy (all at p < 0.001). Higher generalized self-efficacy was related to increased physical activity (p < 0.010). Higher future time perspective (p < 0.001) and generalized self-efficacy (p = 0.48) were associated with lower AD risk score. Subjective cognitive decline (SCD) was associated with lower self-efficacy, ability to delay gratification, and a less expansive future time perspective. Greater self-efficacy and perceived future time remaining were associated with lower AD risk and greater engagement in physical activity. SCD was associated with health beliefs that may negatively affect engagement in positive brain health behaviors. Assessment of and psychoeducation about these intrapersonal health belief constructs may be important targets for behavioral interventions to reduce AD risk.