Subjective Cognitive Decline and Genetic Propensity for Dementia beyond Apolipoprotein ε4: A Systematic Review.

Subjective cognitive decline (SCD) has been described as a probable early stage of dementia, as it has consistently appeared to precede the onset of objective cognitive impairment. SCD is related to many risk factors, including genetic predisposition for dementia. The Apolipoprotein (APOE) ε4 allele, which has been thoroughly studied, seems to explain genetic risk for SCD only partially. Therefore, we aimed to summarize existing data regarding genetic factors related to SCD, beyond APOE ε4, in order to improve our current understanding of SCD. We conducted a PRISMA systematic search in PubMed/MEDLINE and Embase databases using the keywords "subjective cognitive decline" and "genetic predisposition" with specific inclusion and exclusion criteria. From the 270 articles identified, 16 were finally included for the qualitative analysis. Family history of Alzheimer's disease (AD) in regard to SCD was explored in eight studies, with conflicting results. Other genes implicated in SCD, beyond APOE ε4, were investigated in six studies, which were not strong enough to provide clear conclusions. Very few data have been published regarding the association of polygenic risk for AD and SCD. Thus, many more genes related to AD must be studied, with polygenic risk scores appearing to be really promising for future investigation.

Subjective Cognitive Complaints in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are not fully known. OBJECTIVE: We aimed to determine the prevalence, clinical correlates, and predictive value of SCCs in PD. METHODS: We conducted a systematic review and meta-analysis. From 204 abstracts, we selected 31 studies (n = 3441 patients), and from these, identified the prevalence, clinical features, associations with neuropsychiatric symptoms, and predictive values of SCCs in PD. RESULTS: The meta-analysis showed an SCC prevalence of 36%. This prevalence, however, was significantly moderated by study heterogeneity regarding female sex, disease severity, levodopa equivalent daily dosage, exclusion from the overall sample of patients with objective cognitive impairment, and measurement instrument. SCC prevalence did not differ between de novo and treated PD patients. SCCs were weakly and negligibly associated with cognitive changes on objective testing in cross-sectional studies. However, in cognitively healthy patients, SCCs had a risk ratio of 2.71 for later cognitive decline over a mean follow-up of 3.16 years. Moreover, SCCs were moderately related to co-occurring symptoms of depression, anxiety, or apathy and were more strongly related to these neuropsychiatric symptoms than objective cognitive functioning. CONCLUSION: Our analyses suggest that SCCs in patients with and without objective cognitive impairment are frequent, occurring in more than one third of PD patients. Establishing uniform measurement instruments for identifying PD-related SCCs is critical to understand their implications. Even in cases lacking evidence of objective cognitive impairment and where SCCs might reflect underlying neuropsychiatric symptoms, the possibility of later cognitive deterioration should not be excluded. Therefore, SCCs in PD patients warrant close monitoring for opportunities for targeted and effective interventions. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Greater subjective cognitive decline severity is associated with worse memory performance and lower entorhinal cerebral blood flow in healthy older adults.

OBJECTIVE: Subjective cognitive decline (SCD) is a potential early risk marker for Alzheimer's disease (AD), but its utility may vary across individuals. We investigated the relationship of SCD severity with memory function and cerebral blood flow (CBF) in areas of the middle temporal lobe (MTL) in a cognitively normal and overall healthy sample of older adults. Exploratory analyses examined if the association of SCD severity with memory and MTL CBF was different in those with lower and higher cardiovascular disease (CVD) risk status. METHODS: Fifty-two community-dwelling older adults underwent magnetic resonance imaging, neuropsychological testing, and were administered the Everyday Cognition Scale (ECog) to measure SCD. Regression models investigated whether ECog scores were associated with memory performance and MTL CBF, followed by similar exploratory regressions stratified by CVD risk status (i.e., lower vs higher stroke risk). RESULTS: Higher ECog scores were associated with lower objective memory performance and lower entorhinal cortex CBF after adjusting for demographics and mood. In exploratory stratified analyses, these associations remained significant in the higher stroke risk group only. CONCLUSIONS: Our preliminary findings suggest that SCD severity is associated with cognition and brain markers of preclinical AD in otherwise healthy older adults with overall low CVD burden and that this relationship may be stronger for individuals with higher stroke risk, although larger studies with more diverse samples are needed to confirm these findings. Our results shed light on individual characteristics that may increase the utility of SCD as an early risk marker of cognitive decline.

Internalizing and somatic symptoms influence the discrepancy between subjective and objective cognitive difficulties in adults with ADHD who have valid and invalid test scores.

OBJECTIVES: This study investigated the relationship between various intrapersonal factors and the discrepancy between subjective and objective cognitive difficulties in adults with attention-deficit hyperactivity disorder (ADHD). The first aim was to examine these associations in patients with valid cognitive symptom reporting. The next aim was to investigate the same associations in patients with invalid scores on tests of cognitive symptom overreporting. METHOD: The sample comprised 154 adults who underwent a neuropsychological evaluation for ADHD. Patients were divided into groups based on whether they had valid cognitive symptom reporting and valid test performance (n = 117) or invalid cognitive symptom overreporting but valid test performance (n = 37). Scores from multiple symptom and performance validity tests were used to group patients. Using patients' scores from a cognitive concerns self-report measure and composite index of objective performance tests, we created a subjective-objective discrepancy index to quantify the extent of cognitive concerns that exceeded difficulties on objective testing. Various measures were used to assess intrapersonal factors thought to influence the subjective-objective cognitive discrepancy, including demographics, estimated premorbid intellectual ability, internalizing symptoms, somatic symptoms, and perceived social support. RESULTS: Patients reported greater cognitive difficulties on subjective measures than observed on objective testing. The discrepancy between subjective and objective scores was most strongly associated with internalizing and somatic symptoms. These associations were observed in both validity groups. CONCLUSIONS: Subjective cognitive concerns may be more indicative of the extent of internalizing and somatic symptoms than actual cognitive impairment in adults with ADHD, regardless if they have valid scores on cognitive symptom overreporting tests.

Subjective cognitive complaints and objective cognitive impairment in patients suspected of obstructive sleep apnea who underwent polysomnography.

OBJECTIVES: Obstructive sleep apnea (OSA) is linked to cognitive impairment. We aimed to investigate subjective cognitive complaints (SCCs) and objective cognitive scores and their relation to polysomnography (PSG) parameters in patients suspected of having OSA. METHODS: A prospective cohort cross-sectional study was conducted at Siriraj Hospital. Patients suspected of OSA who were scheduled for PSG were recruited. Cognition was assessed using the Montreal Cognitive Assessment (MoCA) and Color Trails Test (CTT). The Memory Index Score (MIS) was calculated from the MoCA. Subjective cognitive complaint presence was assessed through direct questioning of patients and by employing the Cognitive Change Index rated by self or informants (CCI-I). Patients with severe dementia were excluded. RESULTS: Among 258 patients (mean age 61.46 ± 7.05 years, 51.2% female), the mean MoCA score was 23.89 ± 3.89. Based on PSG results, patients were categorized into groups as follows: those without OSA or with mild OSA (combined total of 20.1%), moderate OSA (28.3%), or severe OSA (51.6%). Cognitive Change Index rated by self and CCI-I scores correlated significantly (r = 0.238, p = 0.019) but not with the MoCA score or CTT time. Objective cognitive scores were associated with PSG parameters: total sleep time (TST), sleep onset latency, wake after sleep onset, sleep stages, mean O2 saturation, and time spent with SaO2 below 90% (all p < 0.05). Subjective cognitive scores were not associated with PSG parameters, except CCI-I with TST. Participants with objective cognitive impairment had lower education, higher body mass index, more comorbidities, and lower SCC percentage (all p < 0.05). Patients with moderate to severe OSA had a higher proportion of objective cognitive impairment (64.1%) but a lower incidence of SCC (38.3%) than patients with no OSA or mild OSA. Thirty patients with severe OSA and cognitive impairment received continuous positive airway pressure (CPAP) treatment for a mean of 12.2 months. These patients showed MoCA and MIS improvement, but no significant changes were observed in their CTT and Cognitive Change Index scores. CONCLUSIONS: Most patients with OSA had objective cognitive impairment, but SCC was less frequent in patients with more severe OSA. Several PSG parameters correlated with cognitive scores but not with subjective cognitive scores. Patients with severe OSA may benefit cognitively from CPAP treatment.

Biological and psychological predictors of cognitive function in breast cancer patients before surgery.

PURPOSE: Research suggests that cancer-related cognitive impairment (CRCI) can occur before breast cancer (BC) treatment. The limited extant evidence suggests the underlying mechanisms could be stress-related. Potential psychological and biological predictors of CRCI prior to any BC treatment were examined. METHODS: 112 treatment-naïve women with BC and 67 healthy controls (HC) completed a neuropsychological test battery to assess cognitive impairment and a self-report battery to assess cognitive complaints, cancer-related stress, depressive and anxiety symptoms. Morning and evening cortisol and α-amylase were collected from saliva. Multilinear regressions were conducted. RESULTS: Treatment-naïve BC patients were more frequently impaired in verbal memory and processing speed and reported more cognitive complaints (all p < .001) than HC. BC patients and HC did not differ in overall cognitive impairment (p = .21). Steeper α-amylase, lower cancer-related stress and younger age was associated with better overall cognitive function in treatment-naïve BC patients. Higher depressive symptoms predicted higher levels of cognitive complaints in BC patients. CONCLUSION: Overall, these findings suggest that stress plays a role in CRCI. This study is the first to associate α-amylase with cognitive function in cancer patients, informing future research. The findings on impairment in processing speed and verbal memory among treatment-naïve BC highlight the need to screen for such impairments among BC patients and indicate that future studies on CRCI should include baseline assessments prior to BC treatment. If replicated, these findings could inform the development and testing of appropriate interventions to decrease CRCI among cancer patients. CLINICAL TRIALS REGISTRATION NUMBER: NCT04418856, date of registration: 06.05.2020.

Cut-off point development for the Everyday Memory Questionnaire - Revised in perimenopausal women.

OBJECTIVE: Subjective cognitive complaints have been reported in women during perimenopause and the Everyday Memory Questionnaire - Revised (EMQ-R) has been recently evaluated as a standardized instrument to measure subjective cognitive changes. The purpose of this study was to identify potential cut-off points for the EMQ-R retrieval subscale and attentional subscale, and to assess the validity of these cut-off points in detecting objective cognitive changes associated with reported subjective cognitive complaints. METHOD: After screening, 232 perimenopausal women were included in the analyses. The supervised classification and regression tree was applied to identify optimal cut-off points. Its performance was evaluated by the value of the receiver operating characteristics curve, sensitivity and specificity. RESULTS: Findings revealed that the optimal cut-off point for the attentional subscale was 7, and for the retrieval subscale was 13. Both cut-off points presented acceptable discrimination performance. An independent t-test indicated that both cut-off points were associated with significant differences in scores on neuropsychological measures of retrieval (episodic memory and verbal fluency) as well as neuropsychological measures of higher-level attention (working memory). CONCLUSION: The identified cut-off points may be helpful for women to track or quantify their subjective experiences of brain fog or cognitive symptoms during the menopause transition.

Unveiling the role of subjective cognitive complaints in predicting cognitive impairment in Parkinson´s Disease- A longitudinal study with 4 year of follow up.

BACKGROUND: Emerging data associated subjective cognitive complaints (SCC) with a heightened risk of future cognitive decline in Parkinson´s Disease (PD). OBJECTIVE: To determine whether SCC may predict the development of cognitive impairment in PD patients at baseline. METHODS: Over 4 years, major aspects of motor and non-motor symptoms were assessed. SCC were evaluated by non-motor symptoms scale domain-5 (NMSS5). The predictor value of SCC in cognitive change was assessed with univariate linear regression analyses, with NMSS5 at baseline as predictor. Change in cognition (ΔMoCA) was calculated by subtracting Montreal Cognitive Assessment Scale (MoCA) scores at baseline from scores obtained at reassessment and employed as the outcome. We replicated these analyses by employing alterations in MoCA subdomains as outcomes. RESULTS: 134 patients were evaluated at baseline, of those 73 PD patients were reassessed four years later. In our study, SCC didn´t act as a predictor for future cognitive decline. However, baseline NMSS5 was associated significantly with variation in attention, naming, and orientation domains. CONCLUSION: Our findings did not support that SCC in PD patients acts as a predictor of global cognitive decline. However, our findings enhance comprehension of how SCC correlates with performance in distinct cognitive areas, thereby providing better guidance for patients on their current complaints.

Psychometric properties and normative data of the Italian version of the Cognitive Function at Work Questionnaire: a screening tool for detecting subjective cognitive complaints at work.

INTRODUCTION: Considering the extension of working life due to socioeconomic and political factors, many people may experience cognitive complaints (CC) at their workplace, with severe consequences on their quality of life. The identification of workers reporting significative SCC is crucial to eventually address them to an objective neuropsychological evaluation and implement cognitive interventions to guarantee workers' well-being. Since no Italian questionnaires for detecting CC were designed for occupational settings, the aim of the study was to validate the Italian version of the Cognitive Function at Work Questionnaire (CFWQ) and to provide its normative data. MATERIALS AND METHODS: Internal consistency, convergent and divergent validity, and factorial structure of the CFWQ were evaluated. A regression-based procedure served to compute percentiles of CFWQ and its subscales. RESULTS: Four hundred twenty-one participants without psychiatric and/or neurological disorders completed the survey. We found that the Italian CFWQ included 26 items, with a good internal consistency (Cronbach's alpha = 0.897) and a six-factor structure (memory, language, processing speed, abstract thinking/behavioral control, behavioral inertia, planning ability). CFWQ score did not correlate with empathy but correlated strongly with memory scores and moderately with anxiety and depression scores. CONCLUSIONS: The Italian CFWQ showed good psychometric properties, in analogy with the original English scale. Therefore, it can be successfully employed in organizational contexts to possibly identify workers with CC and therefore with possible co-occurrent psychological, behavioral, and cognitive consequences.

A Biopsychosocial Approach to Persistent Post-COVID-19 Fatigue and Cognitive Complaints: Results of the Prospective Multicenter NeNeSCo Study.

OBJECTIVE: To evaluate whether psychological and social factors complement biomedical factors in understanding post-COVID-19 fatigue and cognitive complaints. Additionally, to incorporate objective (neuro-cognitive) and subjective (patient-reported) variables in identifying factors related to post-COVID-19 fatigue and cognitive complaints. DESIGN: Prospective, multicenter cohort study. SETTING: Six Dutch hospitals. PARTICIPANTS: 205 initially hospitalized (March-June 2020), confirmed patients with SARS-CoV-2, aged ≥18 years, physically able to visit the hospital, without prior cognitive deficit, magnetic resonance imaging (MRI) contraindication, or severe neurologic damage post-hospital discharge (N=205). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Nine months post-hospital discharge, a 3T MRI scan and cognitive testing were performed and patients completed questionnaires. Medical data were retrieved from medical dossiers. Hierarchical regression analyses were performed on fatigue severity (Fatigue Severity Scale; FSS) and cognitive complaints (Cognitive Consequences after Intensive Care Admission; CLC-IC; dichotomized into CLC-high/low). Variable blocks: (1) Demographic and premorbid factors (sex, age, education, comorbidities), (2) Illness severity (ICU/general ward, PROMIS physical functioning [PROMIS-PF]), (3) Neuro-cognitive factors (self-reported neurological symptoms, MRI abnormalities, cognitive performance), (4) Psychological and social factors (Hospital Anxiety and Depression Scale [HADS], Utrecht Coping List, Social Support List), and (5) Fatigue or cognitive complaints. RESULTS: The final models explained 60% (FSS) and 48% (CLC-IC) variance, with most blocks (except neuro-cognitive factors for FSS) significantly contributing. Psychological and social factors accounted for 5% (FSS) and 11% (CLC-IC) unique variance. Higher FSS scores were associated with younger age (P=.01), lower PROMIS-PF (P<.001), higher HADS-Depression (P=.03), and CLC-high (P=.04). Greater odds of CLC-high were observed in individuals perceiving more social support (OR=1.07, P<.05). CONCLUSIONS: Results show that psychological and social factors add to biomedical factors in explaining persistent post-COVID-19 fatigue and cognitive complaints. Objective neuro-cognitive factors were not associated with symptoms. Findings highlight the importance of multidomain treatment, including psychosocial care, which may not target biologically-rooted symptoms directly but may reduce associated distress.

Cognitive complaints in patients with untreated obstructive sleep apnea versus patients with neurological and respiratory diseases: prevalence, severity and risk factors.

PURPOSE: Little is known about cognitive complaints (self-reported problems in cognitive functioning) in patients with Obstructive Sleep Apnea (OSA). We compared the prevalence and severity of cognitive complaints in patients with untreated OSA to patients with neurological and respiratory diseases. We also studied risk factors for cognitive complaints across these diseases, including OSA. METHODS: We used a convenience sample to compare untreated OSA patients (N = 86) to patients with stroke (N = 166), primary brain tumor (N = 197) and chronic obstructive pulmonary disease (COPD, N = 204) on cognitive complaints (Cognitive Failure Questionnaire, CFQ), anxiety and depression (Hospital Anxiety and Depression Scale, HADS) and cognitive impairments using neuropsychological tests. We combined all patient groups (OSA, stroke, brain tumor and COPD) and studied potential risk factors (demographic variables, anxiety, depression and cognitive impairments) for cognitive complaints across all patient groups using regression analysis. RESULTS: The prevalence of cognitive complaints was higher in OSA patients and complaints of forgetfulness and distractibility were more severe compared to stroke and primary brain tumor patients, but similar to or lower than COPD patients. Regression analysis for the combined sample of all patient groups showed that cognitive complaints were most strongly associated with symptoms of anxiety and depression. CONCLUSION: A high rate of OSA reported clinically significant cognitive complaints, comparable to other respiratory and neurological patients. Symptoms of anxiety and depression are important risk factors for cognitive complaints in patients with various neurological and respiratory diseases. Future studies should examine the relation between anxiety, depression and cognitive complaints in patients with OSA.

Interaction between visual impairment and subjective cognitive complaints on physical activity impairment in U.S. older adults: NHANES 2005-2008.

BACKGROUND/AIM: To investigate the independent relationships of visual impairment (VI) and Subjective cognitive complaints (SCC) with physical function impairment (PFI) and the interaction effect between VI and SCC on PFI in American older adults. METHODS: The data of this cross-sectional study was obtained from the 2005-2008 National Health and Examination Survey (NHANES) conducted in the United States. The VI criterion included both subjective self-reported eyesight conditions and objective visual acuity test results. The self-reported questionnaires were utilized to determine PFI and SCC. According to the survey design of NHANS, original data were weighted to produce nationally representative estimates. Both the unweighted original data and weighted estimates underwent analysis. Crude and adjusted logistic models were employed to assess the pairwise associations among VI, SCC, and PFI. To assess the interactive effect, measures such as the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated. RESULTS: A total of 2,710 subjects (weighted n = 38,966,687) aged 60 years or older were included. Compared with subjects without subjective visual impairment (SVI), those with SVI had a significant positive association with PFI [weighted OR (95%CI): 3.11 (2.25, 4.31)]. After multi-variable adjusting, the relationship remained significant [weighted OR (95%CI): 1.90 (1.32, 2.72)]. Similarly, those with objective visual impairment (OVI) were positively associated with the risk of PFI in the crude model [weighted OR (95%CI): 2.35 (1.53, 3.61)] and adjusted model [weighted OR (95%CI): 1.84 (1.07, 3.17)]. Moreover, we found the association of SCC with an increased risk of FPI [crude weighted OR (95%CI): 5.02 (3.40, 7.40); adjusted weighted OR (95%CI): 3.29 (2.01, 5.38)]. Ultimately, the additive interaction showed there was a significant positive interaction term between SVI and SCC on PFI, while OVI and SCC did not. CONCLUSION: Both VI and SCC were significantly associated with PFI in elder adults. Besides, there was a significant synergistic interaction between SVI and SCC on PFI, which indicated the improvement of SVI and SCC may be beneficial for the prevention of PFI. For the elderly, especially those with multiple disabilities, comprehensive and targeted approaches are imperative to foster their overall well-being and health.

Exploring the Cognitive Profiles of Haemodialysis Patients using Objective and Subjective Indicators: A Cross-sectional Observational Study.

BACKGROUND: Cognitive impairment is common in haemodialysis patients and associated with adverse health outcomes. Previous work focused primarily on neuropsychological tests, the gold standard measure of cognition. However, these tests reflect performance under optimal conditions rather than performance in everyday life. This study aims to assess both objective and subjective cognition in haemodialysis patients. METHODS: Adult haemodialysis patients completed measures of objective cognitive impairment (Montreal Cognitive Assessment), subjective cognitive complaints, mood and fatigue symptoms, and provided sociodemographic information. Clinical data such as comorbidity were extracted from patients' medical record. RESULTS: A total of 268 haemodialysis patients (mean age = 59.87 years; 42.5% female) participated. Only 25.0% of the sample had normal cognition, while the rest had either objective cognitive impairments or clinically significant cognitive complaints, or both (both objective impairments and subjective complaints: 26.1%; objective impairments without complaint: 38.4%; significant complaints without objective impairments: 10.4%). Lower education was associated with the presence of objective cognitive impairments, whereas depression was associated with the presence of clinically significant cognitive complaints. Patients who exhibited both objective cognitive impairments and significant cognitive complaints were more likely to have diabetes and higher dialysis dose (Kt/V). Patients with objective cognitive impairments but no significant complaints were significantly older. CONCLUSIONS: The cognitive burden of haemodialysis patients can be manifested as objective impairments and/or subjective complaints. When combined the two indicators may better represent the overall cognitive well-being in this population. There is a need to screen for cognitive difficulties and develop cognitive rehabilitative strategies in dialysis settings.

Compensatory strategy use in diverse older adults with subjective cognitive complaints.

OBJECTIVES: The current study aimed to evaluate the relationship between subjective cognitive complaints (SCC) and compensatory strategy (CS) use in a diverse sample of non-Latinx White (NLW), Black, and Latinx American older adults. METHOD: 807 older adults (Mage = 65.38, 62.7% female) were recruited through Amazon's Mechanical Turk (MTurk) and Qualtrics Panel to complete questionnaires on SCC and CS use. Kruskall-Wallis tests were used to evaluate differences in SCC across groups given non-normal distributions. Analysis of variance (ANOVA) was used to evaluate group differences in CS use. The PROCESS macro for SPSS was used to examine whether demographic factors moderated the relationship between SCC and CS use. RESULTS: NLWs reported higher levels of SCC and greater overall use of CS in comparison to Latinx and Black individuals. Several demographic and psychosocial factors including age, ethno-racial group, education, and anxiety level were found to be associated with CS use. Education was found to moderate the association between SCC and CS use. CONCLUSION: Inconsistent with prior studies, our study found that NLWs reported the highest levels of SCC. CS were used across all racial/ethnic groups, but the frequency of CS use may be impacted by education level. While all education groups increased their CS in response to higher levels of SCC, this increase was more substantial for those with lower levels of education. Future work should consider individuals' cultural and educational background when examining SCC and/or developing CS-based intervention for the aging population.

Mid-life adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and late-life subjective cognitive complaints in women.

INTRODUCTION: Evidence is limited on the role of mid-life Dietary Approaches to Stop Hypertension (DASH) diet in late-life subjective cognitive complaints (SCCs). METHODS: We included 5116 women (mean age in 1985-1991: 46 years) from the New York University Women's Health Study. SCCs were assessed from 2018 to 2020 (mean age: 79 years) by a 6-item questionnaire. RESULTS: Compared to women in the bottom quartile of the DASH scores, the odds ratio (OR) for having two or more SCCs was 0.83 (95% confidence interval: 0.70-0.99) for women in the top quartile of DASH scores at baseline (P for trend = 0.019). The association was similar with multiple imputation and inverse probability weighting to account for potential selection bias. The inverse association was stronger in women without a history of cancer (P for interaction = 0.003). DISCUSSION: Greater adherence to the DASH diet in mid-life was associated with lower prevalence of late-life SCCs in women.

The pattern of cortical thickness associated with executive dysfunction in MCI and SCC: The MEMENTO cohort.

BACKGROUND: The association between the pattern of cortical thickness (CT) and executive dysfunction (ED) in mild cognitive impairment (MCI) and subjective cognitive complaints (SCC) is still poorly understood. We aimed to investigate the association between CT and ED in a large French cohort (MEMENTO) of 2323 participants with MCI or SCC. METHODS: All participants with available CT and executive function data (verbal fluency and Trail Making Test [TMT]) were selected (n=1924). Linear regressions were performed to determine relationships between executive performance and the brain parenchymal fraction (BPF) and CT using FreeSurfer. RESULTS: The global executive function score was related to the BPF (sß: 0.091, P<0.001) and CT in the right supramarginal (sß: 0.060, P=0.041) and right isthmus cingulate (sß: 0.062, P=0.011) regions. Literal verbal fluency was related to the BPF (sß: 0.125, P<0.001) and CT in the left parsorbitalis region (sß: 0.045, P=0.045). Semantic verbal fluency was related to the BPF (sß: 0.101, P<0.001) and CT in the right supramarginal region (sß: 0.061, P=0.042). The time difference between the TMT parts B and A was related to the BPF (sß: 0.048, P=0.045) and CT in the right precuneus (sß: 0.073, P=0.019) and right isthmus cingulate region (sß: 0.054, P=0.032). CONCLUSIONS: In a large clinically based cohort of participants presenting with either MCI or SCC (a potential early stage of Alzheimer's disease [AD]), ED was related to the BPF and CT in the left pars orbitalis, right precuneus, right supramarginal, and right isthmus cingulate regions. This pattern of lesions adds knowledge to the conventional anatomy of ED and could contribute to the early diagnosis of AD.

Frailty in people 50 years or older living with HIV: A sex perspective.

OBJECTIVE: To estimate prefrailty and frailty prevalence and associated factors in people living with HIV (PLHIV) from a sex perspective. METHODS: Cross-sectional study on PLHIV at specialized public health centres in Brazil. Data were obtained from individuals aged ≥50 years using antiretroviral therapy (ART) and with an undetectable viral load through personal interviews, clinical evaluations and medical records. Frailty and prefrailty were characterized using the Fried Frailty Phenotype tool. Multinomial regression models were performed, and the associated factors were selected through the backward stepwise method. RESULTS: Among 670 patients, 373 men and 297 women were included. The prevalence of frailty and prefrailty was significantly higher for women (16.2% and 56.2%, respectively) than for men (11.5% and 46.4%, respectively). Low socioeconomic and educational level, multimorbidity, depression, subjective cognitive complaints, and low scores on the Mini-Mental State Exam (MMSE) were associated (P < 0.05) with frailty for both sexes. However, in the sex-specific analysis, while smoking (OR = 3.66, 95% CI: 1.58-8.48) and a history of low adherence to ART (OR = 3.10, 95% CI: 1.33-7.23) were associated with frailty in men, depression (OR = 3.39, 95% CI: 1.36- 8.44) and the absence of functional dentition (OR = 3.77, 95% CI: 1.36- 10.43) were associated with frailty in women. CONCLUSIONS: This study adds self-reported cognitive complaints as a potential predictor of frailty in both sexes and supports the known deleterious effect of multimorbidity on frailty in adults living with HIV. Furthermore, it suggests that other possible predictors, such as depression, oral health status and adherence to ART, may be sex-specific.

Presence and Persistence of Perceived Subjective Cognitive Complaints and Incident Mild Cognitive Impairments Among Community-Residing Older Adults.

OBJECTIVES: To examine whether Subjective Cognitive Complaints (SCCs) predicted incident mild cognitive impairment (MCI). DESIGN: Prospective Study. SETTING: Central Control of Mobility and Aging (CCMA), a cohort study of community-residing older adults. PARTICIPANTS: Participants were dementia-free community-residing older adults. MEASUREMENTS: SCCs were assessed at the baseline and via bi-monthly structured phone interviews during the first year using the Ascertain Dementia 8 (AD8). Nonpersistent status required one or two SCCs endorsements and Persistent status required three or more SCCs endorsements. Outcome, presence of mild cognitive impairments (MCI) was determined by established case conference diagnostic procedures. Participants were followed annually. Generalized estimating equations (GEE), logistic model type, were used to determine the odds of developing MCI during follow-up. SCCs served as the three-level predictor (no/nonpersistent/persistent) and cognitive status (MCI versus normal) as the binary outcome. Analyses were adjusted for age, sex, education, race, health status, depressive symptoms, and global cognition. RESULTS: The sample (n=454; mean age=75.67 ± 6.43; %female=55.3) included 245 participants who reported no SCCs, 156 who reported 1-2 SCCs, and 53 who reported 3 or more SCCs. Sixty-eight participants developed MCI during follow-up. Results showed that compared to no SCCs, persistent SCCs, and nonpersistent SCCs were significantly associated with increased odds of developing MCI during follow-up. CONCLUSIONS: The presence of SCCs regardless of their persistence was associated with increased odds of developing MCI even when adjusting for objectively-assessed cognitive performance.

Rostral-middle locus coeruleus integrity and subjective cognitive decline in early old age.

OBJECTIVES: Abnormal tau, a hallmark Alzheimer's disease (AD) pathology, may appear in the locus coeruleus (LC) decades before AD symptom onset. Reports of subjective cognitive decline are also often present prior to formal diagnosis. Yet, the relationship between LC structural integrity and subjective cognitive decline has remained unexplored. Here, we aimed to explore these potential associations. METHODS: We examined 381 community-dwelling men (mean age = 67.58; SD = 2.62) in the Vietnam Era Twin Study of Aging who underwent LC-sensitive magnetic resonance imaging and completed the Everyday Cognition scale to measure subjective cognitive decline along with their selected informants. Mixed models examined the associations between rostral-middle and caudal LC integrity and subjective cognitive decline after adjusting for depressive symptoms, physical morbidities, and family. Models also adjusted for current objective cognitive performance and objective cognitive decline to explore attenuation. RESULTS: For participant ratings, lower rostral-middle LC contrast to noise ratio (LCCNR) was associated with significantly greater subjective decline in memory, executive function, and visuospatial abilities. For informant ratings, lower rostral-middle LCCNR was associated with significantly greater subjective decline in memory only. Associations remained after adjusting for current objective cognition and objective cognitive decline in respective domains. CONCLUSIONS: Lower rostral-middle LC integrity is associated with greater subjective cognitive decline. Although not explained by objective cognitive performance, such a relationship may explain increased AD risk in people with subjective cognitive decline as the LC is an important neural substrate important for higher order cognitive processing, attention, and arousal and one of the first sites of AD pathology.

Subjective Complaints are Similar in Subjective Cognitive Decline and Early-Stage Alzheimer's Disease when Assessed in a Memory Clinic Setting.

BACKGROUND: Subjective cognitive complaints are generally poorly associated with objective memory functioning in older persons. Subjective cognitive decline (SCD) is a key feature in SCD and amnestic mild cognitive impairment (aMCI) which both can represent early Alzheimer's disease (AD). The aim of this study was to assess how memory clinic patients with SCD, MCI and mild AD dementia scored on 3 different complaint measures and if the format of assessment had an impact on the association with cognitive functioning, age, and depressive symptoms. METHODS: We included 17 SCD patients, 17 aMCI patients, 17 patients with mild AD, and 30 controls. Complaints were assessed with the Cognitive Change Index (CCI), the Subjective Memory Complaints (SMC) scale, and the Memory Complaint Questionnaire (MAC-Q). RESULTS: There were no significant differences between the total scores in the patient groups on the questionnaires. However, significant differences were found in the number of patients classified with impairment when using the CCI, the SMC, and the MAC-Q. Scores on all questionnaires were significantly associated with depressive symptoms, and significant associations with age, gender, and Addenbrookes Cognitive Examination score were found for the SMC. In patients with cognitive dysfunction, lower memory awareness significantly predicted fewer cognitive complaints. CONCLUSIONS: SCD patients in a memory clinic setting report the same degree of cognitive impairment as patients with aMCI and mild dementia, and in a hospital-based cohort we extend previous findings from healthy controls, that definition of SCD may depend on the format of assessment.