Subjective Cognitive Decline Group Research Articles

Longitudinal assessment of plasma biomarkers for early detection of cognitive changes in subjective cognitive decline

BackgroundIndividuals experiencing subjective cognitive decline (SCD) are at an increased risk of developing mild cognitive impairment and dementia. Early identification of SCD and neurodegenerative diseases using biomarkers may help clinical decision-making and improve prognosis. However, few cross-sectional and longitudinal studies have explored plasma biomarkers in individuals with SCD using immunomagnetic reduction.ObjectiveTo identify plasma biomarkers for SCD.MethodsFifty-two participants [38 with SCD, 14 healthy controls (HCs)] underwent baseline assessments, including measurements of plasma Aβ42, Aβ40, t-tau, p-tau, and α-synuclein using immunomagnetic reduction (IMR) assays, cognitive tests and the Mini-Mental State Examination (MMSE). Following initial cross-sectional analysis, 39 individuals (29 with SCD, 10 HCs) entered a longitudinal phase for reassessment of these biomarkers and the MMSE. Biomarker outcomes across different individual categories were primarily assessed using the area under the receiver operating characteristic (ROC) curve. The SCD subgroup with an MMSE decline over one point was compared to those without such a decline.ResultsHigher baseline plasma Aβ1-42 levels significantly discriminated participants with SCD from HCs, with an acceptable area under the ROC curve (AUC) of 67.5% [95% confidence interval (CI), 52.7–80.0%]. However, follow-up and changes in MMSE and IMR data did not significantly differ between the SCD and HC groups (p > 0.05). Furthermore, lower baseline plasma Aβ1-42 levels were able to discriminate SCD subgroups with and without cognitive decline with a satisfied performance (AUC, 75.0%; 95% CI, 55.6–89.1%). At last, the changes in t-tau and Aβ42 × t-tau could differentiate between the two SCD subgroups (p < 0.05).ConclusionBaseline plasma Aβ42 may help identify people with SCD and predict SCD progression. The role of plasma Aβ42 levels as well as their upward trends from baseline in cases of SCD that progress to mild cognitive impairment and Alzheimer’s disease require further investigation.

Structural neuroimaging changes associated with subjective cognitive decline from a clinical sample

BackgroundAlzheimer’s disease (AD) is characterized by progressive deterioration of cognitive functions. Some individuals with subjective cognitive decline (SCD) are in the early phase of the disease and subsequently progress through the AD continuum. Although neuroimaging biomarkers could be used for the accurate and early diagnosis of preclinical AD, the findings in SCD samples have been heterogeneous. This study established the morphological differences in brain magnetic resonance imaging (MRI) findings between individuals with SCD and those without cognitive impairment based on a clinical sample of patients defined according to SCD-Initiative recommendations. Moreover, we investigated baseline structural changes in the brains of participants who remained stable or progressed to mild cognitive impairment or dementia. MethodsThis study included 309 participants with SCD and 43 healthy controls (HCs) with high-quality brain MRI at baseline. Among the 99 subjects in the SCD group who were followed clinically, 32 progressed (SCDp) and 67 remained stable (SCDnp). A voxel-wise statistical comparison of gray and white matter (WM) volume was performed between the HC and SCD groups and between the HC, SCDp, and SCDnp groups. XTRACT ATLAS was used to define the anatomical location of WM tract damage. Region-of-interest (ROI) analyses were performed to determine brain volumetric differences. White matter lesion (WML) burden was established in each group. ResultsVoxel-based morphometry (VBM) analysis revealed that the SCD group exhibited gray matter atrophy in the middle frontal gyri, superior orbital gyri, superior frontal gyri, right rectal gyrus, whole occipital lobule, and both thalami and precunei. Meanwhile, ROI analysis revealed decreased volume in the left rectal gyrus, bilateral medial orbital gyri, middle frontal gyri, superior frontal gyri, calcarine fissure, and left thalamus. The SCDp group exhibited greater hippocampal atrophy (p < 0.001) than the SCDnp and HC groups on ROI analyses. On VBM analysis, however, the SCDp group exhibited increased hippocampal atrophy only when compared to the SCDnp group (p < 0.001). The SCD group demonstrated lower WM volume in the uncinate fasciculus, cingulum, inferior fronto-occipital fasciculus, anterior thalamic radiation, and callosum forceps than the HC group. However, no significant differences in WML number (p = 0.345) or volume (p = 0.156) were observed between the SCD and HC groups. ConclusionsThe SCD group showed brain atrophy mainly in the frontal and occipital lobes. However, only the SCDp group demonstrated atrophy in the medial temporal lobe at baseline. Structural damage in the brain regions was anatomically connected, which may contribute to early memory decline.

Impaired lexical access for unique entities in individuals with subjective cognitive decline

Subjective cognitive decline (SCD) may serve as an early indicator of Alzheimer’s disease (AD). However, accurately quantifying cognitive impairment in SCD is challenging, mainly because existing assessment tools lack sensitivity. This study examined how tasks specifically designed to assess knowledge of famous people, could potentially aid in identifying cognitive impairment in SCD. A total of 60 adults with SCD and 60 healthy controls (HCs) aged 50 to 82 years performed a famous people verbal fluency task and a famous people naming task. In the famous people fluency task, the results showed that the individuals with SCD produced significantly fewer famous names in the total time allowed than the HCs, and this difference was also found in the first and the second time interval. In the famous people naming task, the performance of the SCD group was significantly lower than that of the HC group only in the more recent period of fame. Overall, these results suggest that retrieving the names of famous people was more difficult for people with SCD than for people without cognitive complaints. They also suggest that famous people verbal fluency and naming tasks could be useful in detecting cognitive decline at the preclinical stage of AD.

Correlation Between Prefrontal Functional Connectivity and the Degree of Cognitive Impairment in Alzheimer's Disease: A Functional Near-Infrared Spectroscopy Study.

The development of Alzheimer's disease (AD) can be divided into subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. Early recognition of pre-AD stages may slow the progression of dementia. This study aimed to explore functional connectivity (FC) changes of the brain prefrontal cortex (PFC) in AD continuum using functional near-infrared spectroscopy (fNIRS), and to analyze its correlation with cognitive function. All participants underwent 48-channel fNIRS at resting-state. Based on Brodmann partitioning, the PFC was divided into eight subregions. The NIRSIT Analysis Tool (v3.7.5) was used to analyze mean ΔHbO2 and FC. Spearman correlation analysis was used to examine associations between FC and cognitive function. Compared with HC group, the mean ΔHbO2 and FC were different between multiple subregions in the AD continuum. Both mean ΔHbO2 in the left dorsolateral PFC and average FC decreased sequentially from SCD to MCI to AD groups. Additionally, seven pairs of subregions differed in FC among the three groups: the differences between the MCI and SCD groups were in heterotopic connectivity; the differences between the AD and SCD groups were in left intrahemispheric and homotopic connectivity; whereas the MCI and AD groups differed only in homotopic connectivity. Spearman correlation results showed that FCs were positively correlated with cognitive function. These results suggest that the left dorsolateral PFC may be the key cortical impairment in AD. Furthermore, there are different resting-state prefrontal network patterns in AD continuum, and the degree of cognitive impairment is positively correlated with reduced FC strength.

A network approach to subjective cognitive decline: Exploring multivariate relationships in neuropsychological test performance across Alzheimer's disease risk states

Subjective cognitive decline (SCD) is characterized by subjective concerns of cognitive change despite test performance within normal range. Although those with SCD are at higher risk for developing further cognitive decline, we still lack methods using objective cognitive measures that reliably distinguish SCD from cognitively normal aging at the group level. Network analysis may help to address this by modeling cognitive performance as a web of intertwined cognitive abilities, providing insight into the multivariate associations determining cognitive status. Following previous network studies of mild cognitive impairment (MCI) and Alzheimer's dementia (AD), the current study centered upon the novel visualization and analysis of the SCD cognitive network compared to cognitively normal (CN) older adult, MCI, and AD group networks. Cross-sectional neuropsychological data from CIMA-Q and COMPASS-ND cohorts were used to construct Gaussian graphical models for CN (n = 122), SCD (n = 207), MCI (n = 210), and AD (n = 79) groups. Group networks were explored in terms of global network structure, prominent edge weights, and strength centrality indices. CN and SCD group networks were contrasted using the Network Comparison Test. Results indicate that CN and SCD groups did not differ in univariate cognitive performance or global network structure. However, measures of strength centrality, principally in executive functioning and processing speed, showed a CN-SCD-MCI gradient where subtle differences within the SCD network suggest that SCD is an intermediary between CN and MCI stages. Additional results may indicate a distinctiveness of network structure in AD, a reversal in network influence between age and general cognitive status as clinical impairment increases, and potential evidence for cognitive reserve. Together, these results provide evidence that network-specific metrics are sensitive to cognitive performance changes across the dementia risk spectrum and can help to objectively distinguish SCD group cognitive performance from that of the CN group.

Altered dynamic amplitude of low-frequency fluctuation in individuals at high risk for Alzheimer's disease.

The brain's dynamic spontaneous neural activity is significant in supporting cognition; however, how brain dynamics go awry in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains unclear. Thus, the current study aimed to investigate the dynamic amplitude of low-frequency fluctuation (dALFF) alterations in patients at high risk for Alzheimer's disease and to explore its correlation with clinical cognitive assessment scales, to identify an early imaging sign for these special populations. A total of 152 participants, including 72 SCD patients, 44 MCI patients and 36 healthy controls (HCs), underwent a resting-state functional magnetic resonance imaging and were assessed with various neuropsychological tests. The dALFF was measured using sliding-window analysis. We employed canonical correlation analysis (CCA) to examine the bi-multivariate correlations between neuropsychological scales and altered dALFF among multiple regions in SCD and MCI patients. Compared to those in the HC group, both the MCI and SCD groups showed higher dALFF values in the right opercular inferior frontal gyrus (voxel P < .001, cluster P < .05, correction). Moreover, the CCA models revealed that behavioural tests relevant to inattention correlated with the dALFF of the right middle frontal gyrus and right opercular inferior frontal gyrus, which are involved in frontoparietal networks (R = .43, P = .024). In conclusion, the brain dynamics of neural activity in frontal areas provide insights into the shared neural basis underlying SCD and MCI.

Data‐driven analysis of most common neurodegenerative dementias reveals atrophy patterns associated with overlapping cognitive symptoms

AbstractBackgroundA precise understanding of the neuroanatomical basis of clinical manifestation of dementia is an important step for timely diagnosis. Dementia due to proteinopathies, such as Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and Frontotemporal dementia (FTD), have different yet overlapping atrophy patterns which could account for their overlapping clinical presentations. To disentangle these relationships and facilitate timely differential diagnosis, we estimated distinct and overlapping atrophy patterns and associated them with cognitive deficits.MethodWe included 1702 AD (age = 66.1±8.3), 319 FTD (age = 63.3±7.7), 213 DLB (age = 69.7±7.0), and 1330 subjective cognitive decline (SCD) (age = 59.8±9.0) participants from the Amsterdam Dementia Cohort. MRIs were processed with Freesurfer and outputs were manually checked. Scanner‐related bias in outputs was corrected using NeuroHarmony pipeline. Participants’ cognition was evaluated using standardized neuropsychological tests. Z‐scores for cognitive domains of memory, executive functioning, attention, language, and visuospatial functioning were derived using SCD group as reference. We estimated distinct and overlapping atrophy patterns in each disease by computing odds ratio in each region, using SCD group as reference. Furthermore, we computed group‐wise Pearson partial correlation between the (sub‐)cortical measures and cognition while correcting for confounding effects of age, sex, and education level.ResultAtrophy in bilateral inferior temporal, and right hippocampus was more prevalent in AD and FTD patients than in DLB patients (Figures 1‐3). Temporal pole atrophy was more prevalent in FTD than in AD or DLB patients. Superior parietal and supra marginal atrophy was more prevalent in AD than in FTD or DLB patients. Bilateral hippocampus and amygdala atrophy associated with memory impairment in AD, whereas left hemisphere atrophy associated with memory impairment in FTD. Frontal atrophy associated with worse executive functioning and attention in FTD, but not in AD. Language deficit associated with left temporal lobe atrophy in both FTD and AD. Visuospatial dysfunction associated with parietal lobe atrophy in both AD and FTD. In DLB, we observed no significant correlation between atrophy and cognitive deficits.ConclusionWe identified distinct and overlapping atrophy patterns and associations of atrophy patterns with cognitive deficits in AD, FTD, and DLB. These data‐driven insights are crucial for accurate diagnosis and prognosis.

Examining the Driving Habits of Older Canadians as Captured by the COMPASS‐ND Study

AbstractBackgroundDriving is associated with a sense of autonomy and good quality of life in older adults. However, older adults often change their driving habits, such as regulating how often, how far, and under what conditions (e.g., time of day, weather) they drive, in part due to changes in cognition. Our study describes data from the first large‐scale Canadian cohort study to investigate differences in driving habits across cognitive groups, including cognitively healthy older adults (control), Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI), and Alzheimer’s Disease (AD).MethodWe analyzed data from the Comprehensive Assessment of Neurodegeneration and Dementia study (COMPASS‐ND, Chertkow et al., 2019), a population‐based study of Canadians with various cognitive and functional abilities (May 2021 Data Release). The final sample analyzed included 317 participants (55% Females, Meanage = ∼72). We report the responses for the following driving‐related questions: licensing status (no longer have license, drive with or without restrictions), driving frequency, driving distance, and driving restrictions (e.g., bad weather).ResultMost participants across all groups reported that they have a driver’s license without restrictions, including the AD group (AD: ∼61%, remaining groups: &gt;90%). The following analyses only included current drivers. In terms of the frequency of driving and the distance travelled, as expected, the AD group drove the least often and the shortest distances. The most frequent restriction types selected by all groups were bad weather and nighttime driving. The number of restriction types increased with the severity of cognitive decline. Interestingly, driving restrictions reported by the SCD group more closely approximated the cognitively impaired groups (MCI and AD) than the control group.ConclusionAlthough many of the AD group participants still had a license, they also reported the greatest number of driving restrictions. Further, the SCD group and MCI group were quite similar in their responses for several items, indicating that even SCD may be associated with differences in driving habits. Implications of driving‐related limitations include reduced independence, socialization, participation, and access to resources (e.g., medical care, groceries).

The effect of psychosocial state in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer’s disease: A cross‐sectional study

AbstractBackgroundSocial support and mental health are important issues in the context of elderly care. Social support is beneficial to both mental health and cognition. The purpose of this study was to investigate the effect of social support and mental health in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and Alzheimer´s disease (AD).MethodIn this cross‐sectional, observational study, participants were 219 people between 45 and 93 (mean age = 61.82; SD = 10.13), and divided into three cognitive groups (SCD, MCI, AD). Neuropsychological assessment and psychological questionnaires were used for data collection and analysis.ResultThe SCD group and MCI group scored higher than patients with AD on the Adult Mental Health Scale (AMHS) and the Social Support Rating Scale (SSRS). The results of this study suggest that the degree of cognitive impairment of middle‐aged and old people is affected by age and education level, and is related to the level of social support and mental health status (P&lt;0.05).ConclusionThe level of social support, mental health and cognitive decline are closely related in patients with cognitive impairments. Therefore, it is very important to give early intervention to middle‐aged and old people with poor mental health status and social support status, so as to delay the progression of cognitive impairment.

T1w/T2w MRI ratio brain signature across degenerative syndromes and their cognitive impairment continuum and mixed presentations

AbstractBackgroundWe aimed to investigate the ratio’s signature in diverse clinically‐defined neurodegenerative syndromes and their cognitive impairment continuum. Our hypothesis was that higher cognitive impairment would be associated with lower cortical T1w/T2w ratio in all clinical subtypes.MethodWe used standardized MRI data obtained from participants in the COMPASS‐ND study of the Canadian Consortium on Neurodegeneration in Aging. T1w images were resampled down to T2w resolution; after co‐registration, intensities were standardized between 1‐100 and the ratio computed. Brain segmentation was then performed using FreeSurfer 6.0 on T1w images with the Desikan‐Killiany‐Tourville and default subcortical atlases. Participants included 109 cognitively intact elderly (CIE), 131 subjective cognitive decline (SCD), 252 mild cognitive impairment (MCI), 113 vascular‐MCI (V‐MCI), 55 mixed vascular‐Alzheimer’s dementia (V‐AD), 76 Alzheimer’s disease (AD), 21 Lewy‐body dementia (LBD), 33 fronto‐temporal‐dementia (FTD), 77 Parkinson’s disease (PD), 35 PD‐MCI and nine PD with dementia (PDD). Since the between‐vendor distributions differed (Fig1), Z scores were computed separately for each scanner vendor (GE, Philips, or Siemens) with CIE as a reference group. ANCOVA with age as covariate and FDR correction were conducted between each group and CIE.ResultNo significant effect of age was observed. Compared to CIE, significantly higher T1w/T2w ratios were observed in SCD for most of the brain (57/86 regions), in MCI for six frontal areas only, while decline was observed in AD throughout the brain (Fig1). V‐MCI showed lower ratios in subcortical areas only while V‐AD had pronounced lower ratios in subcortical areas as well as in 11 cortical areas. PD had marked lower ratios throughout the brain with the exception of an intact corpus callosum (Fig2). Contrariwise, FTD only displayed a lower ratio in the corpus callosum whereas PD‐MCI and LBD did not show any significant difference with CIE.ConclusionWe observed clear distinct patterns of T1w/T2w ratios for SCD, MCI, AD and PD groups. Since this ratio does not seem specific to a neural biological substrate, the meaning of these differences remains to be determined. Nevertheless, these results suggest that simple MRI measures such as the T1w/T2w ratio can highlight underlying mechanisms in various neurodegenerative processes.

Distinct Neural Correlates of Anxiety and Depression in Subjective Cognitive Decline versus Healthy Aging, a Microstructural Diffusion MRI Study

AbstractBackgroundA common criticism of considering Subjective Cognitive Decline (SCD) as a preclinical stage of Alzheimer’s Disease is that it may be explained by depression or anxiety1. We used NODDI, a diffusion microstructural model2, to explore the pathophysiology of depression and anxiety in SCD versus controls.Method325 participants in the Cam‐CAN study 3 (127 SCD) older than 55 were included in the analysis. Diffusion imaging data was collected on a 3T Siemens TIM Trio scanner with a 32‐channel head coil for 0, 1000 and 2000 s/mm2 b‐values and 30 gradient directions. Preprocessing and calculation of the NODDI metric Intracellular Volume Fraction (ICVF) were completed using MRTrix3, AMICO and MATLAB. The hippocampal cingulum bundle and fornix regions of interest (ROIs)4 were extracted from the ICBM‐DTI‐81 atlas. Depression and anxiety were assessed using the Hamilton Anxiety and Depression Scale (HADS). Linear regression models were completed in R. Gender and age were included as nuisance variables.ResultThere were no differences in gender or age distribution between cohorts, however participants with SCD were more depressed and anxious on average (Table 1). There was a significant interaction effect between depression and cohort in the fornix (Figure 1), as well as between anxiety and cohort in the hippocampal cingulum (Figure 2). In post‐hoc analyses, only the SCD group showed a correlation between depression and ICVF in the fornix (Figure 1) while only controls showed a correlation between anxiety and ICVF in the hippocampal cingulum (Figure 2), indicating different pathophysiology underlying psychiatric symptoms in the two groups.ConclusionAnxiety and depression appear to be associated with different microstructural features in SCD versus controls, suggesting anxiety and depression in SCD is a phenomenon distinct from anxiety and depression in healthy aging. Future work will explore the relationship between anxiety and depression and risk of conversion to mild cognitive impairment.1. Mitchell AJ, Beaumont H, Ferguson D, et al. Acta Psychiatrica Scandinavica. 2014;130(6):439‐51.2. Daducci A, Canales‐Rodriguez EJ, Zhang H, et al. Neuroimage. 2015;105:32‐44.3. Shafto MA, Tyler LK, Dixon M, et al. BMC neurology. 2014;14(1):1‐25.4. Kantarci K. Frontiers in Aging Neuroscience. 2014;6.

Distinct Neural Correlates of Anxiety and Depression in Subjective Cognitive Decline versus Healthy Aging, a Microstructural Diffusion MRI Study

AbstractBackgroundA common criticism of considering Subjective Cognitive Decline (SCD) as a preclinical stage of Alzheimer’s Disease is that it may be explained by depression or anxiety1. We used NODDI, a diffusion microstructural model2, to explore the pathophysiology of depression and anxiety in SCD versus controls.Method325 participants in the Cam‐CAN study 3 (127 SCD) older than 55 were included in the analysis. Diffusion imaging data was collected on a 3T Siemens TIM Trio scanner with a 32‐channel head coil for 0, 1000 and 2000 s/mm2 b‐values and 30 gradient directions. Preprocessing and calculation of the NODDI metric Intracellular Volume Fraction (ICVF) were completed using MRTrix3, AMICO and MATLAB. The hippocampal cingulum bundle and fornix regions of interest (ROIs)4 were extracted from the ICBM‐DTI‐81 atlas. Depression and anxiety were assessed using the Hamilton Anxiety and Depression Scale (HADS). Linear regression models were completed in R. Gender and age were included as nuisance variables.ResultThere were no differences in gender or age distribution between cohorts, however participants with SCD were more depressed and anxious on average (Table 1). There was a significant interaction effect between depression and cohort in the fornix (Figure 1), as well as between anxiety and cohort in the hippocampal cingulum (Figure 2). In post‐hoc analyses, only the SCD group showed a correlation between depression and ICVF in the fornix (Figure 1) while only controls showed a correlation between anxiety and ICVF in the hippocampal cingulum (Figure 2), indicating different pathophysiology underlying psychiatric symptoms in the two groups.ConclusionAnxiety and depression appear to be associated with different microstructural features in SCD versus controls, suggesting anxiety and depression in SCD is a phenomenon distinct from anxiety and depression in healthy aging. Future work will explore the relationship between anxiety and depression and risk of conversion to mild cognitive impairment. • Mitchell AJ, Beaumont H, Ferguson D, et al. Acta Psychiatrica Scandinavica. 2014;130(6):439‐51. • Daducci A, Canales‐Rodriguez EJ, Zhang H, et al. Neuroimage. 2015;105:32‐44. • Shafto MA, Tyler LK, Dixon M, et al. BMC neurology. 2014;14(1):1‐25. • Kantarci K. Frontiers in Aging Neuroscience. 2014;6.

Changes in Multiparametric Magnetic Resonance Imaging and Plasma Amyloid-Beta Protein in Subjective Cognitive Decline.

The association between plasma amyloid-beta protein (Aβ) and subjective cognitive decline (SCD) remains controversial. We aimed to explore the correlation between neuroimaging findings, plasma Aβ, and neuropsychological scales using data from 53 SCD patients and 46 age- and sex-matched healthy controls (HCs). Magnetic resonance imaging (MRI) was used to obtain neuroimaging data for a whole-brain voxel-based morphometry analysis and cortical functional network topological features. The SCD group had slightly lower Montreal Cognitive Assessment (MoCA) scores than the HC group. The Aβ42 levels were significantly higher in the SCD group than in the HC group (p < 0.05). The SCD patients demonstrated reduced volumes in the left hippocampus, right rectal gyrus (REC.R), and right precentral gyrus (PreCG.R); an increased percentage fluctuation in the left thalamus (PerAF); and lower average small-world coefficient (aSigma) and average global efficiency (aEg) values. Correlation analyses with Aβ and neuropsychological scales revealed significant positive correlations between the volumes of the HIP.L, REC.R, PreCG.R, and MoCA scores. The HIP.L volume and Aβ42 were negatively correlated, as were the REC.R volume and Aβ42/40. PerAF and aSigma were negatively and positively correlated with the MoCA scores, respectively. The aEg was positively correlated with Aβ42/40. SCD patients may exhibit alterations in plasma biomarkers and multi-parameter MRI that resemble those observed in Alzheimer's disease, offering a theoretical foundation for early clinical intervention in SCD.

39 The role of Subjective Cognitive Decline and Aging Perceptions in Help Seeking across White and Non-White older adults

Objective:Research has indicated that racial and ethnic minoritized groups in the United States are disproportionately affected by dementia (e.g., Alzheimer’s disease), and seek help (HS) later in the disease course, if at all. It has also been posited that individuals from different ethno-racial groups have divergent perceptions of the aging process, which may influence HS. These disparities warrant tailored preventive efforts to encourage identification of factors which contribute to HS to enable earlier psychoeducation and enhanced access to resources. The factors which influence HS may differ across ethnoracial groups. Here we examine the relative influence of subjective cognitive decline (SCD), a risk factor for AD, and aging perceptions to HS in these groups.Participants and Methods:The current sample consisted of 161 healthy older adults (51 Male, 110 Female), aged 51 to 92 (M=73.43, SD=6.85) with a mean education of 16 years (SD=2.3 years) who performed &gt; -1.5 SD on clinical neuropsychological testing. 26.7% of the sample self-reported as race/ethnic minorities (e.g., Hispanic or Non-Hispanic African American, Asian, Other.) Participants completed a 20-item SCD questionnaire assessing perceived cognitive difficulties in comparison to same aged peers, in addition to measures assessing HS behavior, (e.g., Have you gone to the doctor specifically for memory concerns?), and aging perceptions (e.g., older adulthood group identification, explicit stereotypes, essentialism). Point biserial correlations examined relationships between SCD, HS and aging perceptions, and multinomial logistic regressions examined the contribution of SCD and aging perceptions to HS across majority (White) and minoritized groups (Non-White participants).Results:In bivariate analyses of the White participant group, HS was associated with SCD (r=0.43, p&lt;0.001) and age group identification (r=0.27, p&lt;0.01), and the latter were also associated (r=-0.19, p&lt;0.05). The logistic regression model correctly classified 86% of participants (same as null), explaining a relatively small proportion of variance in HS, Snell R2 = 0.09, Nagelkerke’s R2 = 0.16. Age group identification was not associated with HS (b=-0.02, SE=0.26, p=0.94, 95% CI [0.59, 1.63] but SCD was (p=0.04). In the non-White group (n=42), bivariate analyses showed that HS was associated with essentialism (r=-0.41, p&lt;0.01; belief aging as a fixed and inevitable process)) and explicit stereotypes (r=-0.42, p&lt;0.01) but not with SCD (r=0.21, p=0.19). SCD was also associated with essentialism (p=-0.32, p&lt;0.05), stereotypes (p=0.32, p&lt;0.05), and age group identification (r=0.38, p&lt;0.01). The regression model correctly classified 88.9% of participants (same as null); neither SCD (p=0.39), explicit stereotypes (p=0.43), essentialism (p=0.72), nor age group identification (p=0.62) contributed to HS when all were considered.Conclusions:When both SCD and age perceptions are examined together as predictors of HS, SCD alone predicts HS in the majority group. Neither construct predicts HS in the minoritized group—despite significant bivariate associations between HS, aging perceptions and SCD that varied across ethno-racial groups. Findings illustrate that SCD and aging perceptions may contribute differently to HS across ethno-racial groups in the US, and as such may indicate different priorities when implementing HS tools (e.g., screeners for detection of cognitive impairment). Ongoing work is addressing illness perceptions, another key barrier in HS in these groups to further inform on tailoring of services.

2 Predictors of Memory Deficits in Patients with Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer’s Disease - Do Disease Severity Moderate the Association?

Objective:Age, sex, education, memory, and the APOE e4 allele are related to Alzheimer’s disease (AD) risk. Recently it was suggested that low body mass index (BMI) contributes to the development of AD. The objective of this study was to examine how delayed recall of a word list was influenced by demographic variables, APOE and BMI in people with memory problems, and to investigate whether the impact of these variables was smaller at higher disease severity levels.Participants and Methods:The participants were 1206 patients in the Norwegian NorCog registry diagnosed with either subjective cognitive decline (SCD) (n=274), mild cognitive impairment (MCI) (n=444), or AD (n=488). ANOVAs and hierarchical regression were applied to examine whether the delayed recall part of the 10-word test of the CERAD-WL was associated with age, sex, education, APOE (e4/non-e4) and BMI. Analyses were run separately for SCD, MCI and AD patients.Results:There were significant bivariate differences (p&lt;.001) between the three patient groups for all variables; the AD patients were older, less educated, more were women, more had APOE e4 alleles, and they had lower BMI. For the SCD group, 34% of the total variance (R2) of the dependent variable was explained. All independent variables except BMI (p=.07) had a significant contribution in the prediction. For MCI, 18% of the total were explained. All variables except education and sex showed significant contribution to R2. For the AD group, R2 was 13%. Sex and BMI did not contribute significantly.Conclusions:As expected, the performance on CERAD-WML was influenced by age, education and sex in the SCD group, whereas the associations between memory function and the three demographic variables were less clear among patients with MCI and AD. ApoE genotype influenced on the CERAD-WML results among all patients, whereas BMI only influenced on the results among patients with SCD and MCI. Our findings do not support that BMI is associated with delayed recall of memory in AD.

Using Cognitive-Motor Dual-Tasks and Functional Near-Infrared Spectroscopy to Characterize Older Adults with and without Subjective Cognitive Decline.

Subjective cognitive decline (SCD) refers to individuals who report persistent cognitive deficits but perform normally on neuropsychological tests. Performance may be facilitated by increased prefrontal cortex activation, known as neural compensation, and could be used to differentiate between older adults with and without SCD. This cross-sectional pilot study measured changes in the hemodynamic response (ΔHbO2) using functional near-infrared spectroscopy (fNIRS) as well as cognitive and motor performance during fine and gross motor dual-tasks in older adults with and without SCD. Twenty older adults over 60 years old with (n = 10) and without (n = 10) SCD were recruited. Two experiments were conducted using 1) gross motor walking and 2) fine motor finger tapping tasks that were paired with an n-back working memory task. Participants also completed neuropsychological assessments and questionnaires on everyday functioning. Repeated measures ANOVAs demonstrated slower response times during dual-task gait compared to the single task (p = 0.032) and in the non-SCD group, slower gait speed was also observed in the dual compared to single task (p = 0.044). Response times during dual-task finger tapping were slower than the single task (p = 0.049) and greater ΔHbO2 was observed overall in the SCD compared to non-SCD group (p = 0.002). Examining neural and performance outcomes revealed differences between SCD and non-SCD groups and single and dual-tasks. Greater brain activation during dual-task finger tapping may reflect neural compensation, which should be examined in a larger sample and longitudinally to better characterize SCD.

Neurocognitive Characteristics of Subjective Cognitive Decline and Its Association with Objective Cognition, Negative Emotion, and Sleep Quality in Chinese Elderly.

Subjective cognitive decline (SCD) is recognized as a preclinical indicatorof Alzheimer's disease (AD), and this stage provides a valuable time window for ultra-early intervention in AD. The aim of this study was to investigate the neurocognitive characteristics of SCD and its correlation with objective cognition, negative emotion and sleep quality in Chinese elderly. A total of 1200 volunteers aged 60 and older underwent Brief Elderly Cognitive Screening Inventory, Quick Cognitive Screening Scale for the Elderly, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index and Core Neuropsychological Test. According to the examination results, the participants were divided into healthy control (HC) and SCD groups. The neurocognitive function of SCD and its relationship with objective cognition, negative emotion and sleep quality were analyzed. Compared with the HC group, the SCD group had similar global cognitive function but slightly impaired neurocognitive function. After adjusting for confounding factors such as age, sex, marriage, education and chronic disease, neurocognitive function (Picture-Symbol Matching: OR=0.167, 95% CI: 0.105-0.266; Word Stem Completion: OR =0.260, 95% CI: 0.131-0.514; Trail Making Test: OR=0.315, 95% CI: 0.178-0.560; Picture Recall: OR =0.278, 95% CI: 0.122-0.636), negative emotion (sub-depressive symptoms: OR=2.287, 95% CI: 1.483-3.527; sub-anxiety symptoms: OR=1.663, 95% CI: 1.079-2.563), and poor sleep quality (OR=2.138, 95% CI: 1.571-2.909) were significantly correlated with the occurrence of SCD. The study illustrates that SCD is closely related to objective cognition, negative emotion and sleep quality. Clinical evaluation and follow-up of SCD should fully account for these factors.

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.

Hippocampal Volume and Episodic Associative Memory Identify Memory Risk in Subjective Cognitive Decline Individuals in the CIMA-Q Cohort, Regardless of Cognitive Reserve Level and APOE4 Status.

Subjective cognitive decline (SCD) was proposed to identify older adults who complain about their memory but perform within a normal range on standard neuropsychological tests. Persons with SCD are at increased risk of dementia meaning that some SCD individuals experience subthreshold memory decline due to an underlying progression of Alzheimer's disease (AD). Our main goal was to determine whether hippocampal volume and APOE4, which represent typical AD markers, predict inter-individual differences in memory performance among SCD individuals and can be used to identify a meaningful clinical subgroup. Neuropsychological assessment, structural MRI, and genetic testing for APOE4 were administered to one hundred and twenty-five older adults over the age of 65 from the CIMAQ cohort: 66 SCD, 29 individuals with mild cognitive impairment (MCI), and 30 cognitively intact controls (CTRLS). Multiple regression models were first used to identify which factor (hippocampal volume, APOE4 allele, or cognitive reserve) best predicted inter-individual differences in a Face-name association memory task within the SCD group. Hippocampal volume was found to be the only and best predictor of memory performance. We then compared the demographic, clinical and cognitive characteristics of two SCD subgroups, one with small hippocampal volume (SCD/SH) and another with normal hippocampal volume (SCD/NH), with MCI and CTRLS. SCD/SH were comparable to MCI on neuropsychological tasks evaluating memory (i.e., test of delayed word recall), whereas SCD/NH were comparable to CTRLS. Thus, using hippocampal volume allows identification of an SCD subgroup with a cognitive profile consistent with a higher risk of conversion to AD.

Evaluation of glymphatic system activity using diffusion tensor image analysis along the perivascular space and amyloid PET in older adults with objectively normal cognition: a preliminary study.

Diffusion tensor image analysis along the perivascular space (DTI-ALPS) is a recently introduced method for the assessment of the glymphatic system without the need for contrast injection. The purpose of our study was to assess the glymphatic system in cognitively normal older adults with or without subjective cognitive decline (SCD) using DTI-ALPS, and correlating with amyloid PET. To evaluate the glymphatic system in cognitively normal older adults using DTI-ALPS, we built a prospective cohort including a total of 123 objectively cognitively normal older adults with or without SCD. The ALPS index was calculated from DTI MRI and was assessed by correlating it with standardized uptake value ratios (SUVRs) from amyloid PET and clinically relevant variables. The study subjects were also divided into amyloid "positive" and "negative" groups based on the result of amyloid PET, and the ALPS indices between those two groups were compared. The ALPS index was not significantly different between the normal and SCD groups (P = 0.897). The mean ALPS index from the amyloid positive and amyloid negative group was 1.31 and 1.35, respectively, which showed no significant difference (P = 0.308). Among the SUVRs from variable cortices, that of the paracentral cortex was negatively correlated with the ALPS index (r = -0.218, P = 0.016). Multivariate linear regression revealed that older age (coefficient, -0.007) and higher SUVR from the paracentral cortex (coefficient, -0.101) were two independent variables with a significant association with a lower ALPS index (P = 0.015 and 0.045, respectively). DTI-ALPS may not be useful for evaluation of the glymphatic system in subjects with SCD. Older age was significantly associated with lower ALPS index. Greater amyloid deposition in the paracentral cortex was significantly associated with lower glymphatic activity in cognitively normal older adults. These results should be validated in future studies on the relationships between ALPS index and other fundamental compartments in glymphatic system, such as perivenous space and the meningeal lymphatic vessels.