Longitudinal associations between amyloid and symptoms of depression and anxiety in subjective cognitive decline: the impact of personality characteristics.

Subjective cognitive decline is associated with higher anxiety and depression during the COVID‐19‒related confinement

The association between AD biomarkers and neuropsychiatric symptoms in subjective cognitive decline; the SCIENCe project

Is the center for epidemiologic studies depression scale as useful as the geriatric depression scale in screening for late-life depression? A systematic review

Association between SCD‐Plus features and GDS factors in subjective cognitive decline and healthy controls in the studies DELCODE and SILCODE

A-4 Amyloid Status Modifies the Association between Subjective Cognitive Decline and Brain MRI Metrics

Amyloid‐positive individuals with subjective cognitive decline present increased CSF neurofilament light levels that relate to hippocampal volume

Objective:Alzheimer’s disease (AD) pathophysiology, including β-amyloid (Aβ), can be appreciated with molecular PET imaging. Among older adults, the distribution of Aβ standard uptake value ratios (SUVR) is typically bimodal and a diagnostic cut is applied to define those who are amyloid ‘positive’ and ‘negative’. However, it is unclear whether the dynamic range of SUVRs in amyloid positive and negative individuals is meaningful and associated with cognition. Previous work by Insel and colleagues (2020) used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) trial to demonstrate subtle associations between a cortical summary SUVR and cognition, particularly on the Free and Cued Selective Reminding Test (FCSRT). We followed up this study to determine the extent to which regional SUVR is associated with performance on the FCSRT in amyloid positive and negative participants screened for participation in the A4 study.Participants and Methods:We accessed regional Aβ SUVR, including anterior cingulate, posterior cingulate, parietal, precuneus, temporal, and medial/orbital frontal regions, along with FCSRT15 and demographic data from 4492 A4 participants at screening. Participants were coded as amyloid positive (n=1329; 30%) or amyloid negative (n=3169; 70%) based on a summary SUVR of greater than or equal to 1.15. We used separate general linear models to examine the association of total or regional SUVR, amyloid positivity status, and the interaction of SUVR and amyloid status with FCSRT scores. We compared model fits across regions with the Akaike Information Criterion (AIC). We ran post hoc correlational analyses examining the relationship between SUVR and FCSRT scores stratified by amyloid status in the case of significant interactions. Results were similar with and without demographic adjustment.Results:There was a significant interaction of summary and all regional SUVR with FCSRT scores in addition to main effects of amyloid positivity. In all models, there were small negative associations between SUVR and memory in amyloid positive individuals. For amyloid negative individuals, there was a significant and very small negative association between SUVR and FCSRT scores only in the parietal lobes and precuneus regions. Model fits were generally similar across the different analyses.Conclusions:In this sample of individuals screened for a secondary prevention trial of AD, there were consistent associations between Aβ SUVR in all regions and memory for those considered amyloid positive. However, for individuals considered amyloid negative, there were only very small associations between SUVR and memory in parietal and precuneus regions. We conclude that the dynamic range of amyloid may be relevant among those with diagnostic evidence of amyloidosis, but that subtle Aβ accumulation in posterior regions may relate to declining memory in “subthreshold” states.

BackgroundHealth-related quality of life (HR-QoL) is an important outcome for patients and crucial for demonstrating the value of new treatments. Health utility estimates in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are limited, especially in biomarker-confirmed populations. Besides, little is known about the longitudinal HR-QoL trajectory. This study aims to provide health utility estimates for SCD and MCI and investigate the QoL trajectory along the disease continuum.MethodsLongitudinal data from 919 SCD and 1336 MCI patients from the MEMENTO cohort were included. SCD was defined as clinical dementia rating (CDR) = 0, and MCI as CDR = 0.5. HR-QoL was measured using the EQ-5D-3L patient-reported instrument. Linear mixed-effect models (LMM) were used to assess the longitudinal change in HR-QoL and identify predictors of these changes.ResultsBaseline health utilities were 0.84 ± 0.16 and 0.81 ± 0.18, and visual analogue scale (VAS) were 75.8 ± 14.82 and 70.26 ± 15.77 in SCD and MCI. In amyloid-confirmed cases, health utilities were 0.85 ± 0.14 and 0.86 ± 0.12 in amyloid-negative and amyloid-positive SCD, and 0.83 ± 0.17 and 0.84 ± 0.16 in amyloid-negative and amyloid-positive MCI. LMM revealed an annual decline in health utility of − 0.015 (SE = 0.006) and − 0.09 (SE = 0.04) in moderate and severe dementia (P < 0.05). There was a negative association between clinical stage and VAS where individuals with MCI, mild, moderate, and severe dementia were on average 1.695 (SE = 0.274), 4.401 (SE = 0.676), 4.999 (SE = 0.8), and 15.386 (SE = 3.142) VAS points lower than individuals with SCD (P < 0.001). Older age, female sex, higher body mass index, diabetes, cardiovascular history, depression, and functional impairment were associated with poor HR-QoL. Amyloid positivity was associated with an annual decline of − 0.011 (SE = 0.004, P < 0.05) health utility over time.ConclusionsHealth utility estimates from this study can be used in economic evaluations of interventions targeting SCD and MCI. Health utility declines over time in moderate and severe dementia, and VAS declines with advancing clinical stages. Amyloid-positive patients show a faster decline in health utility indicating the importance of considering biomarker status in HR-QoL assessments. Future research is needed to confirm the longitudinal relationship between amyloid status and HR-QoL and to examine the level at which depression and IADL contribute to HR-QoL decline in AD.

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

BackgroundThe COVID-19 pandemic may worsen the mental health of people reporting subjective cognitive decline (SCD) and therefore their clinical prognosis. We aimed to investigate the association between the intensity of SCD and anxious/depressive symptoms during confinement and the underlying mechanisms.MethodsTwo hundred fifty cognitively unimpaired participants completed the Hospital Anxiety and Depression Scale (HADS) and SCD-Questionnaire (SCD-Q) and underwent amyloid-β positron emission tomography imaging with [18F] flutemetamol (N = 205) on average 2.4 (± 0.8) years before the COVID-19 confinement. During the confinement, participants completed the HADS, Perceived Stress Scale (PSS), Brief Resilience Scale (BRS), and an ad hoc questionnaire on worries (access to primary products, self-protection materials, economic situation) and lifestyle changes (sleep duration, sleep quality, eating habits). We investigated stress-related measurements, worries, and lifestyle changes in relation to SCD. We then conducted an analysis of covariance to investigate the association of SCD-Q with HADS scores during the confinement while controlling for pre-confinement anxiety/depression scores and demographics. Furthermore, we introduced amyloid-β positivity, PSS, and BRS in the models and performed mediation analyses to explore the mechanisms explaining the association between SCD and anxiety/depression.ResultsIn the whole sample, the average SCD-Q score was 4.1 (± 4.4); 70 (28%) participants were classified as SCD, and 26 (12.7%) were amyloid-β-positive. During the confinement, participants reporting SCD showed higher PSS (p = 0.035) but not BRS scores (p = 0.65) than those that did not report SCD. No differences in worries or lifestyle changes were observed. Higher SCD-Q scores showed an association with greater anxiety/depression scores irrespective of pre-confinement anxiety/depression levels (p = 0.002). This association was not significant after introducing amyloid-β positivity and stress-related variables in the model (p = 0.069). Amyloid-β positivity and PSS were associated with greater HADS irrespective of pre-confinement anxiety/depression scores (p = 0.023; p < 0.001). The association of SCD-Q with HADS was mediated by PSS (p = 0.01).ConclusionsHigher intensity of SCD, amyloid-β positivity, and stress perception showed independent associations with anxious/depressive symptoms during the COVID-19 confinement irrespective of pre-confinement anxiety/depression levels. The association of SCD intensity with anxiety/depression was mediated by stress perception, suggesting stress regulation as a potential intervention to reduce affective symptomatology in the SCD population in the face of stressors.

BackgroundCaregivers of care-recipients with mild cognitive impairment (MCI) or dementia experience high caregiver burden; however, the psychiatric burden of caregivers of care-recipients with subjective cognitive decline (SCD) has not been investigated. We aimed to explore the prevalence of and risk factors for anxiety and depression symptoms among the caregivers of care-recipients with SCD and cognitive impairment.MethodsThe Hospital Anxiety and Depression Scale (HADS) was used to examine the anxiety and depression symptoms among the caregivers of 343 care-recipients (84 with SCD, 120 with MCI and 139 with dementia) treated at the Memory Clinic of Huashan Hospital in Shanghai, China from May 2012 to October 2014. A logistic regression was used to explore the factors associated with caregiver’s anxiety and depression symptoms.ResultsIn total, 26.5 % of caregivers had anxiety symptoms, and 22.4 % had depression symptoms. Totals of 17.9, 30.0 and 28.8 % of caregivers of care-recipients with SCD, MCI or dementia, respectively, had anxiety symptoms (P = 0.1140), whereas 22.6, 24.2 and 20.9 %, respectively, had depression symptoms (P = 0.8165). The risk factors for caregiver’s anxiety symptoms were increased caregiver age as well as having care-recipients who were male, had higher Cohen Mansfield Agitation Inventory (CMAI) scores, and higher Geriatric Depression Scale (GDS) scores. The risk factors for caregiver’s depression symptoms were increased caregiver age as well as caring for care-recipients with MCI or SCD, those with lower Toronto Empathy Questionnaire (TEQ) scores, and those with higher GDS scores.ConclusionsCaregivers of care-recipients with SCD showed the same level of depression symptoms as those of care-recipients with MCI. Caregiver’s depression and anxiety symptoms were associated with their care-recipients’ psychiatric and behavioral syndromes.

BackgroundDepression is common in rheumatoid arthritis (RA), however reported prevalence varies considerably. Two frequently used instruments to identify depression are the Center for Epidemiological Studies Depression (CES-D) scale, and the Hospital Anxiety and Depression Scale (HADS). The objectives of this study were to test if the CES-D and HADS-D (a) satisfy current modern psychometric standards for unidimensional measurement in an early RA sample; (b) measure the same construct (i.e. depression); and (c) identify similar levels of depression.MethodsData from the two scales completed by patients with early RA were fitted to the Rasch measurement model to show that (a) each scale satisfies the criteria of fit to the model, including strict unidimensionality; (b) that the scales can be co-calibrated onto a single underlying continuum of depression and to (c) examine the location of the cut points on the underlying continuum as indication of the prevalence of depression.ResultsNinety-two patients with early RA (62% female; mean age = 56.3, SD = 13.7) gave 141 sets of paired CES-D and HAD-D data. Fit of the data from the CES-D was found to be poor, and the scale had to be reduced to 13 items to satisfy Rasch measurement criteria whereas the HADS-D met model expectations from the outset. The 20 items combined (CES-D13 and HADS-D) satisfied Rasch model expectations. The CES-D gave a much higher prevalence of depression than the HADS-D.ConclusionThe CES-D in its present form is unsuitable for use in patients with early RA, and needs to be reduced to a 13-item scale. The HADS-D is valid for early RA and the two scales measure the same underlying construct but their cut points lead to different estimates of the level of depression. Revised cut points on the CES-D13 provide comparative prevalence rates.

BackgroundSleep disturbance is common in rheumatoid arthritis (RA). Sleep disturbance is thought to have some influence on psychological state, self-efficacy and Quality of Life (QOL) in patients with RA.ObjectivesTo evaluate...

ObjectivesLittle is known about the experience of family caregivers of patients who require prolonged mechanical ventilation (PMV). We examined the perspectives of caregivers of patients who died after PMV to...

BackgroundNeuropsychiatric symptoms are common in the prodromal phase of dementia, and may be related to altered structure and function of subcortical grey matter involved in emotion regulation. We aimed to determine the association between subcortical grey matter volume and occurrence of neuropsychiatric symptoms in a population‐based study.MethodBetween 2009‐2015 dementia‐free participants from the population‐based Rotterdam Study underwent 1.5T brain MRI. Volumes of the accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus were determined using FreeSurfer 6.1. Symptoms of depression and anxiety were assessed using the Center for Epidemiologic Studies Depression (CES‐D) scale and the anxiety subscale of the Hospital Anxiety and Depression scale (HADS‐A). We determined cross‐sectional associations between subcortical volumes (per 1 standard deviation [SD] decrease) and continuous CES‐D and HADS‐A scores using linear regression, and with clinically significant symptoms (CES‐D≥16;HADS‐A≥8) using logistic regression. Models were adjusted for demographics, lifestyle factors, comorbidities and co‐medication use. We repeated analyses stratifying on cognitive status (healthy/subjective complaints/MCI).ResultOf 3452 participants (mean age 69.3 years, 55.2% women), 284 (8.2%) scored positive for clinical depressive symptoms, and 270 (7.8%) for clinical anxiety symptoms. Smaller hippocampal volume was associated with higher odds of clinical depressive symptoms (odds ratio [95%CI]: 1.27[1.05‐1.52], p = 0.01). In contrast, smaller volumes of the caudate were associated with less depressive symptoms (mean difference in log‐transformed score [95%CI] for caudate: ‐0.06[‐0.10;‐0.02], p&lt;0.01, and pallidum: ‐0.04[‐0.08;0.00], p = 0.05). Smaller volumes of the caudate and pallidum were also associated with less anxiety (caudate: ‐0.04[‐0.07;‐0.01], p&lt;0.01, pallidum: ‐0.05[‐0.09;‐0.02], p&lt;0.01), accompanied for the caudate by a lower odds of clinical anxiety symptoms (OR[95%CI]: 0.84[0.72;0.98], p = 0.03). No associations were observed with the accumbens, amygdala, putamen, or thalamus. Associations were observed in cognitively healthy participants, as well as in those with subjective cognitive complaints or MCI.ConclusionIn community‐dwelling older adults, volumes of the hippocampus, caudate, and pallidum are associated with neuropsychiatric symptoms, which do not differ by neurodegenerative disease stage. These findings support a complex role of subcortical volumes in the occurrence of neuropsychiatric symptoms in the older population.