Subjective Cognitive Impairment Research Articles

Modifiable dementia risk factors associated with objective and subjective cognition.

Early detection of both objective and subjective cognitive impairment is important. Subjective complaints in healthy individuals can precede objective deficits. However, the differential associations of objective and subjective cognition with modifiable dementia risk factors are unclear. We gathered a large cross-sectional sample (N=3327, age 18 to 84) via a smartphone app and quantified the associations of 13 risk factors with subjective memory problems and three objective measures of executive function (visual working memory, cognitive flexibility, model-based planning). Depression, socioeconomic status, hearing handicap, loneliness, education, smoking, tinnitus, little exercise, small social network, stroke, diabetes, and hypertension were all associated with impairments in at least one cognitive measure. Subjective memory had the strongest link to most factors; these associations persisted after controlling for depression. Age mostly did not moderate these associations. Subjective cognition was more sensitive to self-report risk factors than objective cognition. Smartphones could facilitate detecting the earliest cognitive impairments. Smartphone assessments of cognition were sensitive to dementia risk factors. Subjective cognition had stronger links to most factors than did objective cognition. These associations were not fully explained by depression. These associations were largely consistent across the lifespan.

Improving the DSM-5 approach to cognitive impairment: Developmental prosopagnosia reveals the need for tailored diagnoses.

The Diagnostic Statistical Manual of Mental Disorders (DSM-5) recommends diagnosing neurocognitive disorders (i.e., cognitive impairment) when a patient scores beyond -1 SD below neurotypical norms on two tests. I review how this approach will fail due to cognitive tests' power limitations, validity issues, imperfect reliabilities, and biases, before summarizing their resulting negative consequences. As a proof of concept, I use developmental prosopagnosia, a condition characterized by difficulties recognizing faces, to show the DSM-5 only diagnoses 62-70% (n1 = 61, n2 = 165) versus 100% (n1 = 61) through symptoms alone. Pooling the DSM-5 missed cases confirmed the presence of group-level impairments on objective tests, which were further evidenced through meta-analyses, thus validating their highly atypical symptoms. These findings support a paradigm shift towards bespoke diagnostic approaches for distinct cognitive impairments, including a symptom-based method when validated effective. I reject dogmatic adherence to the DSM-5 approach to neurocognitive disorders, and underscore the importance of a data driven, transdiagnostic approach to understanding patients' subjective cognitive impairments. This will ultimately benefit patients, their families, clinicians, and scientific progress.

Neuroimaging Correlates of Post-COVID-19 Symptoms: A Functional MRI Approach

Backgrounds and Purpose: Post-COVID syndrome is characterized by persistent symptoms, including fatigue and cognitive impairment. These symptoms may be experienced by up to 80% of patients. We aimed to identify possible patterns of brain activation underlying post-COVID fatigue. Methods: The study used functional MRI (Siemens MAGNETOM Prisma 3T scanner with a specially created protocol) of the brain in 30 patients with post-COVID fatigue syndrome and 20 healthy volunteers. Task functional MRI (fMRI) was performed using a cognitive paradigm (modified Stroop test). Eligible patients included adults aged 18–50 years with a >12 weeks before enrolment (less than 12 months) prior history of documented COVID-19 with symptoms of fatigue not attributable to any other cause, and with MFI-20 score > 30 and MoCA at first visit. Healthy control participants had no prior history of COVID-19 and negative tests for severe acute coronavirus respiratory syndrome with MFI-20 score < 30 and MoCA at first visit. Task fMRI data were processed using the SPM12 software package based on MATLAB R2022a. Results: Cognitive task fMRI analysis showed significantly higher activation in the post-COVID group versus healthy volunteers’ group. Between-group analysis showed significant activation differences. Using a threshold of T > 3 we identified eight clusters of statistically significant activation: supramarginal gyri, posterior cingulate cortex, opercular parts of precentral gyri and cerebellum posterior lobe bilaterally. Conclusions: Post-COVID fatigue syndrome associated with subjective cognitive impairment could show changes in brain functional activity in the areas connected with information processing speed and quality.

Gut flora reflects potential risk factors for cognitive dysfunction in patients with epilepsy.

This cross-sectional study aims to analyze the differences in gut flora between patients with epilepsy with and without cognitive impairment and normal subjects. One hundred patients with epilepsy who came to our hospital from 2020.12 to 2022.12 (epilepsy group) were selected, and another 100 family members of the patients were selected as the control group (control group). Patients with epilepsy were further classified by the MMSE scale into 62 patients with combined cognitive impairment (Yes group) and 38 patients without cognitive impairment (No group). Detection of gut flora in feces by 16S rRNA high-throughput sequencing. Logistic regression was used to analyze risk factors for cognitive dysfunction in patients with epilepsy. There were more significant differences in the structure and composition of the gut flora between patients in the epilepsy group and the control group, but no significant differences in diversity analysis (P > 0.05). Actinobacteriota, Faecalibacterium and Collinsella were significantly lower in the Yes group than in the No group (P < 0.05), and the Alpha diversity index was numerically slightly smaller than in the No group, with the PCoA analysis demonstrating a more dispersed situation in both groups. Five metabolic pathways, including glycolysis and heterolactic fermentation, were upregulated in the Yes group. LEfSe analysis showed that five groups of bacteria, including Coriobacteriaceae and Collinsella, were selected as marker species for the presence or absence of comorbid cognitive impairment. Of these, Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy combined with cognitive impairment. There was an imbalance in the gut flora of patients with epilepsy compared to healthy controls. The gut flora of patients with epilepsy with cognitive dysfunction differs significantly from that of patients without cognitive dysfunction. Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy with cognitive dysfunction and can be used as an indicator for the observation of epilepsy with cognitive dysfunction.

Subjective cognitive and olfactory impairments predict different prospective dementia outcomes.

Self-reported measures emerge as potential indicators for early detection of dementia and mortality. We investigated the predictive value of different self-reported measures, including subjective cognitive decline (SCD), subjective olfactory impairment (SOI), subjective taste impairment (STI), and self-reported poor health (SPH), in order to determine the risk of progressing to Alzheimer's disease (AD) dementia, Parkinson's disease (PD) dementia, or any-other-cause dementia. A total of 6,028 cognitively unimpaired individuals from the 8th wave of the English Longitudinal Study of Ageing (ELSA) were included as the baseline sample and 5,297 individuals from the 9th wave were included as 2-year follow-up sample. Self-rated measures were assessed using questions from the ELSA structured interview. Three logistic regression models were fitted to predict different the dementia outcomes. SCD based on memory complaints (OR = 11.145; P < 0.001), and older age (OR = 1.108, P < 0.001) significantly predicted the progression to AD dementia at follow-up. SOI (OR = 7.440; P < 0.001) and older age (OR = 1.065, P = 0.035) significantly predicted the progression to PD dementia at follow-up. Furthermore, SCD based on memory complaints (OR = 4.448; P < 0.001) jointly with complaints in other (non-memory) mental abilities (OR = 6.662; P < 0.001), and older age (OR = 1.147, P < 0.001) significantly predicted the progression to dementia of any other cause. Different types of complaints are specifically associated with different dementia outcomes. Our study demonstrates that self-reported measures are a useful and accessible tool when screening for individuals at risk of dementia in the general population.

Micronutrients, Frailty, and Cognitive Impairment: Design and Preliminary Results from the CogLife 2.0 Study.

Among preventive strategies against dementia, nutrition is considered a powerful one and the recently established "nutritional cognitive neuroscience of aging" is a highly active research field. The present study was designed to deeply characterize older adults across the continuum from cognitive integrity to mild cognitive impairment (MCI) and better elucidate the prognostic role of lipophilic micronutrients within their lipidomic signature. 123 participants older than 65 years across the continuum from cognitive integrity to MCI were included [49 with subjective cognitive impairment, 29 women, 72.5±5.4 years, 26 MCI, 9 women, 74.5±5.8 years and 50 without cognitive impairment, 21 women, 70.8±4.3 years]. All participants underwent neuropsychological and nutritional examination as well as comprehensive geriatric assessment with calculation of the Multidimensional Prognostic Index (MPI) as a proxy of frailty and biological age and blood withdrawal for the analyses of lipophilic micronutrients, metabolomics and oxylipidomics. One year after the evaluation, same tests are ongoing. After adjustment for age, sex, daily fruit and vegetable intake and cholesterol, we found a significant positive correlation between lutein and the number of correct words in category fluency (p = 0.016). This result supports the importance of carotenoids as robust biomarkers of cognitive performance independent of the nutritional status and frailty of the participants, as the entire present study collective was robust (MPI 0-0.33). The complete analyses of the metabolome and the oxylipidome will hopefully shed light on the metabolic and prognostic signature of cognitive decline in the rapidly growing population at risk of frailty.

Assessing the Linguistic Capacity Across Alzheimer's Disease and Its Preclinical Stages: Evidence from Narrative Macrostructure in Elderly Speakers of Greek.

The assessment of language deficits can be valuable in the early clinical diagnosis of neurodegenerative disorders, including Alzheimer's disease (AD). The present study aims to explore whether language markers at the macrostructural level could assist with the placement of an individual across the dementia continuum employing production data from structured narratives. We administered a Picture Sequence Narrative Discourse Task to 170 speakers of Greek: young healthy controls (yHC), cognitively intact healthy elders (eHC), elder participants with subjective cognitive impairment (SCI), with mild cognitive impairment (MCI), and with AD dementia at the mild/moderate stages. Structural MRIs, medical history, neurological examination, and neuropsychological/cognitive screening determined the status of each speaker to appropriately groupthem. The data analysis revealed that the Macrostructure Index, Irrelevant Info, and Narration Density markers can track cognitive decline and AD (p < 0.001; Macrostructural Index: eHC versus AD Sensitivity 93.8%, Specificity 74.4%, MCI versus AD Sensitivity 93.8%, Specificity 66.7%; Narration Density: eHC versus AD Sensitivity 90.6%, Specificity 71.8%, MCI versus AD Sensitivity 93.8%, Specificity 66.7%). Moreover, Narrative Complexity was significantly affected for subjects with AD, Irrelevant Info increased in the narrations of speakers with MCI and AD, while Narration Length did not appear to indubitably differentiate between the cognitively intact groups and the clinical ones. Narrative Macrostructure Indices provide valuable information on the language profile of speakers with(out) intact cognition revealing subtle early signs of cognitive decline and AD suggesting that the inclusion of language-based assessment tools would facilitate the clinical process.

The Congruence and Interrelationship: A Dyadic Perspective on the Subjective Cognitive Impairment in the Patients with Colorectal Cancer and Their Spousal Caregivers

ObjectivesPatients with colorectal cancer (CRC) reported experiencing subjective cognitive impairment (SCI), and their spousal caregivers perceived the patients’ SCI. This cross-sectional study assessed the congruence of SCI between the patients’ self-reports and the spousal caregivers’ perceptions and examined the factors affecting SCI from the dyadic perspective. MethodsA total of 200 dyads of patients with CRC and their spousal caregivers were invited to complete the survey, which evaluated the SCI, dyadic coping (DC), quality of life, anxiety, and depression for the dyads. Congruence was analyzed using the intraclass correlation coefficient (ICC) and paired-sample t test. Impacting factors analysis was conducted using Pearson correlations, hierarchical multiple regression, and actor–partner interdependence mediation model. ResultsThe congruency of SCI between the patient-reported and the spouse-perceived ranged from moderate to good (ICC = 0.75 to 0.86). After controlling demographic variables (the patients’ gender and spouses’ work status), the DC of both patients and spousal caregivers, and the emotional health of patients were significant predictors for patients’ SCI (all P < .05). In the actor–partner interdependence mediation model, there was an actor effect between DC and SCI for both patients and spousal caregivers and a partner effect between DC and SCI for patients. Moreover, patients’ emotional health (anxiety and depression) had the mediating effect between DC and SCI for both patients and spousal caregivers. ConclusionSpousal caregivers played a vital role in assessment and management in the SCI of patients. The DC of patients and spousal caregivers and the emotional health of patients (eg, anxiety and depression) were major predictors for the SCI of patients. Implications for NursingNursing providers should consider the importance of patients’ and spousal caregivers’ perspectives in assessing and managing SCI. This study supports nurses focusing on the congruence and interrelationship of SCI to enhance DC for CRC patients and their spousal caregivers. This approach aims to reduce emotional distress and develop cognitive interventions from a dyadic perspective.

Correlation Between Subjective Cognitive Impairment and Self-efficacy for Coping with Cancer Before and During Adjuvant Therapy

Abstract Date Presented 03/22/24 Subjective cognitive impairment (SCI) is a common complaint among cancer patients. High correlation between self-efficacy (SE) before adjuvant treatment started with SCI and depression three month later, suggest that SE should be part of intervention Primary Author and Speaker: Danit Langer Additional Authors and Speakers: Asnat Bar-Haim Erez Contributing Authors: Vered Rubacha Weiss

Distorted time perception in patients with neurocognitive impairment

BackgroundTime perception is known to be distorted in patients with neuropsychiatric disorders. Therefore, this study aims to investigate the correlation between cognitive decline and time distortion by examining time perception in participants with neurocognitive impairment (Alzheimer's disease [AD], vascular dementia [VD], and Parkinson's disease dementia [PDD]) compared to those with subjective cognitive impairment (SCI). MethodsOverall, 569 participants with cognitive decline complaints between 2013 and 2022 were investigated. Participants were subjected to a verbal estimation task, time production task, time comparison task, and neuropsychological assessments. ResultsTime perception abilities were distorted in patients with neurocognitive impairment compared to those with SCI. Despite similar educational backgrounds, the vascular cognitive impairment (VCI)/VD group demonstrated the lowest MMSE scores (22.4 ± 4.2, p-value <0.001) and larger time-estimation errors. Patients with VCI/VD significantly underestimated time in the 35-s (19.6 ± 12.6s) and 60-s (28.7 ± 19.9s) tasks. In the time production task, patients with VCI/VD produced shorter times in their 15-s (12.7 ± 4.3; p-value = 0.001), 30-s (23.6 ± 8.3; p value < 0.001), and 60-s (43.8 ± 18.9; p-value <0.001) trials. In the time comparison task, the VCI/VD group had significantly fewer correct answers than that in the SCI groups (6.0 ± 1.3 vs. 7.1 ± 0.9, p-value <0.001). Correlation analysis revealed that multiple cognitive functions are involved in the time perception tasks. ConclusionsPatients with VCI/VD had the poorest time perception. These findings may provide a modest contribution to understanding the underlying pathophysiology and psychological connections related to temporal abilities in time perception.

Amyloid PET disclosure in subjective cognitive decline: Patient experiences over time.

We disclosed amyloid positron emission tomography (PET) results in individuals with subjective cognitive decline (SCD) and studied patient experiences and outcomes over a 6-month period. Fifty-seven participants from the Subjective Cognitive Impairment Cohort (SCIENCe) (66±8 years, 21 [37%] F, Mini-Mental State Examination 29±1, 15 [26%] amyloid positive [A+]) completed questionnaires 1 week prior (T0), 1 day after (T1), and 6 months after amyloid PET disclosure (T2). Questionnaires addressed patient-reported experiences and outcomes. Independent of amyloid status, participants were satisfied with the consultation (scale 1-10; 7.9±1.7) and information provided (scale 1-4; T1: 3.3±0.9, T2: 3.2±0.8). After 6 months, A+ participants reported more information needs (45%vs. 12%, p=0.02). Independent of amyloid status, decision regret (scale 1-5; A+: 1.5±0.9, A-: 1.4±0.6, p=0.53) and negative emotions (negative affect, uncertainty, anxiety) were low (all p>0.15 and Pinteraction>0.60). Participants with SCD valued amyloid PET disclosure positively, regardless of amyloid status. The need for information after 6 months, which was stronger in A+ individuals, underscores the importance of follow-up. Participants with subjective cognitive decline (SCD) positively valued amyloid positron emission tomography (PET) disclosure. Participants with SCD experienced low levels of decision regret. We did not observe an increase in negative emotions. After 6 months, amyloid-positive individuals wanted more information.

Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Dementia: A Pilot Study.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two major neurodegenerative diseases causing dementia. Due to similar clinical phenotypes, differential diagnosis is challenging without specific biomarkers. Beta-site Amyloid Precursor Protein cleaving enzyme 1 (BACE1) is a β-secretase pivotal in AD pathogenesis. In AD and mild cognitive impairment subjects, BACE1 activity is increased in brain/cerebrospinal fluid, and plasma levels appear to reflect those in the brain. In this study, we aim to evaluate serum BACE1 activity in FTD, since, to date, there is no evidence about its role. The serum of 30 FTD patients and 30 controls was analyzed to evaluate (i) BACE1 activity, using a fluorescent assay, and (ii) Glial Fibrillary Acid Protein (GFAP) and Neurofilament Light chain (NfL) levels, using a Simoa kit. As expected, a significant increase in GFAP and NfL levels was observed in FTD patients compared to controls. Serum BACE1 activity was not altered in FTD patients. A significant increase in serum BACE1 activity was shown in AD vs. FTD and controls. Our results support the hypothesis that serum BACE1 activity is a potential biomarker for the differential diagnosis between AD and FTD.

Hand motor dysfunction is associated with both subjective and objective cognitive impairment across the dementia continuum.

Motor dysfunction is an important feature of early-stage dementia. Gait provides a non-invasive biomarker across the dementia continuum. Gait speed and rhythm aid risk stratification of incident dementia in subjective cognitive impairment (SCI) and associate with cognitive domains in mild cognitive impairment (MCI) and dementia. However, hand movement analysis, which may be more accessible, has never been undertaken in SCI, and rarely in MCI or dementia. We aimed to address this gap and improve understanding of hand motor-cognitive associations across the dementia continuum. 208 participants were recruited: 50 with dementia, 58 MCI, 40 SCI and 60 healthy controls. Consensus diagnoses were made after comprehensive gold-standard assessments. A computer key-tapping test measured frequency, dwell-time, rhythm, errors and speed. Associations between key-tapping and cognitive domains and diagnoses were analysed using regression. Classification accuracy was measured using Area under Receiver-Operating-Characteristic curves. Hand frequency and speed were associated with memory and executive domains (P≤.001). Nondominant hand rhythm was associated with all cognitive domains. Frequency, rhythm and speed were associated with SCI, MCI and dementia. Frequency and speed classified ≥94% of dementia, and ≥88% of MCI, from controls. Rhythm of nondominant hand classified ≥86% of dementia and MCI and 69% of SCI. Our findings show hand motor dysfunction occurs across the dementia continuum and, similar to gait, associates with executive and memory domains, and with cognitive diagnoses. Key-tapping performance differentiated dementia and MCI from healthy controls. More research is required before recommending key-tapping as a non-invasive motor biomarker of cognitive impairment.

A history of abuse is associated with more severe migraine- and pain-related disability: Results from the American Registry for Migraine Research.

Prior studies have established an association between a history of abuse and more severe migraine presentation. This cross-sectional, observational study of a clinic-based migraine population used validated measures to elucidate migraine-specific and migraine-related burdens among patients with a history of abuse. Patients with migraine (n = 866) from the American Registry for Migraine Research self-reported if they had a history of emotional, physical, and/or sexual abuse and completed questionnaires assessing migraine-related burden: Migraine Disability Assessment, Subjective Cognitive Impairment Scale for Migraine Attacks, Work Productivity and Activity Impairment, Patient-Reported Outcomes Measurement Information System Pain Interference, Patient Health Questionnaire-2, and Generalized Anxiety Disorder-7. Migraine-related burden in patients with versus without a history of abuse was compared. Subsequently, a mediation analysis evaluated the impact of depression and anxiety symptoms in the relationship between abuse history and migraine burden. A history of abuse was reported by 36.5% (n = 316/866) of participants. After controlling for patient age, sex, years lived with headache, and headache frequency, a history of abuse was significantly associated with more severe migraine-related disability. The combined burden of depression and anxiety symptoms mediated the relationship. A history of abuse is associated with greater migraine-related disability. Future studies should determine if identification and management of the psychological and physical sequelae of abuse reduce migraine burden.

Methods for assessment of rey auditory verbal learning test performance in memory clinic patients and healthy adults - at the cross-roads of learning theory and clinical utility

Background: Knowledge is still lacking regarding the preferred method for evaluation of learning in the Rey Auditory Verbal Learning Test (RAVLT). Validity of different methods was examined by the effect size in differentiating diagnostic stages in memory clinic patients versus healthy adults and the strength of association between RAVLT performance and brain atrophy. Method: The study included individuals with dementia (n = 247), Mild Cognitive Impairment (MCI, n = 709), Subjective Cognitive Impairment (SCI, n = 175) and cognitively unimpaired adults serving as healthy controls (HC, n = 102). All patients went through a comprehensive clinical examination and neuropsychological assessment of cognition including episodic memory gauged with RAVLT and brain imaging of medial temporal atrophy, cortical atrophy, and white matter hyperintensity. Results: The standard method for evaluation of learning in RAVLT (summed score over five trials) together with the late learning method (mean of trials 4 and 5) were the two most powerful methods according to group differentiation (discriminant validity). Both methods also showed considerable association with medial temporal atrophy (construct validity). The initial RAVLT performance represented by results on trial 1 and the constant in regression analysis with the power function provided information regarding attention that was important for the separation of SCI and HC. Conclusions: The most favorable clinical utility was indicated by discriminant and construct validity by total learning (standard method) including both attention- and learning-related parts and late learning of RAVLT performance, while theoretical understanding of mental processes involved in RAVLT performance was provided by the distinction between initial versus the subsequent learning performance.

The Prognostic Test Accuracy of the Short and Standard Forms of the Montreal Cognitive Assessment.

Cognitive impairment is a critical concern in stroke care, and international guidelines recommend early cognitive screening. The aim of this study was to determine the prognostic accuracy of both the short and standard forms of the Montreal Cognitive Assessment (MoCA) in predicting long-term cognitive recovery following a stroke. For this study, we used data from the Efficacy of Fluoxetine - a Randomized Controlled Trial in Stroke (EFFECTS) study, which encompassed stroke patients from 35 Swedish centers over the period from 2014 to 2019. Cognitive assessments were initially conducted at 2-15 days post-stroke, with follow-up data gathered at 6 months. We used the MoCA for objective cognitive evaluation. For assessing subjective cognitive impairment, we used the memory and thinking domain of the Stroke Impact Scale. For psychometric evaluation of the short Swedish version of MoCA (s-MoCA-SWE), we used cross tables and binary logistic regression. The study included 1,141 patients (62.2% men; median [interquartile range; IQR] age, 72.3 [13.2] years; median [IQR] stroke severity, 3.0 [3.0]). At baseline, the prevalence of cognitive impairment was 71.7% according to the s-MoCA-SWE (≤12) and 67.0% according to the MoCA (≤25). The s-MoCA-SWE demonstrated a sensitivity of 92.3% for correctly identifying patients with objective cognitive impairment and 81.5% for identifying those with subjective impairments at 6 months. Although the s-MoCA-SWE had higher sensitivity, the MoCA had a more balanced sensitivity and specificity in detecting both subjective and objective cognitive impairments. In both crude and multivariable models, the s-MoCA-SWE was more strongly associated than the MoCA with cognitive impairment at 6 months. Both the short and standard versions of the MoCA appear to be effective in identifying individuals likely to experience persistent cognitive issues following a stroke. Considering the limited time available in an acute stroke unit, the short-form version may be more practical. Nevertheless, further prospective studies are required to validate these findings.

Long-term sequelae after viral meningitis and meningoencephalitis are frequent, even in mildly affected patients, a prospective observational study.

An increasing number of studies demonstrate that viral meningitis and meningoencephalitis, even those with a mild course of meningitis, can result in residual sequelae. We aimed to investigate the long-term outcome in both viral meningitis and meningoencephalitis/encephalitis patients and impact of long-term sequelae on patients' social and professional daily lives in a prospective observational study with a follow-up period of 20 months. A total of 50 patients (12% encephalitis, 58% meningoencephalitis and 30% meningitis) and 21 control persons participated in the study. The most common cause was the tick-borne encephalitis (TBE) virus. The most important persistent signs and symptoms after 2 years were subjective cognitive impairment (36%), fatigue and/or excessive daytime sleepiness (31%), disturbed nighttime sleep (31%) and headaches (13%), as well as feeling more rapidly exhausted after cognitive effort (53%). Independent of disease severity in the acute phase, almost one third of patients still reported mildly impaired social and/or professional life due to the long-term sequelae, with scores in the health status assessment still significantly lower compared to healthy controls. Regardless of the severity of the acute illness and despite constant improvement within 2 years, 67% of patients still had persistent signs and symptoms, but these were only relevant to everyday social or professional life in about 30% of these patients.

Cognitive Speed in Neurodegenerative Disease: Comparing Mean Rate and Inconsistency Within and Across the Alzheimer's and Lewy Body Spectra in the COMPASS-ND Study.

Alzheimer's disease (AD) and Lewy body disease (LBD) are characterized by early and gradual worsening perturbations in speeded cognitive responses. Using simple and choice reaction time tasks, we compared two indicators of cognitive speed within and across the AD and LBD spectra: mean rate (average reaction time across trials) and inconsistency (within person variability). The AD spectrum cohorts included subjective cognitive impairment (SCI, n = 28), mild cognitive impairment (MCI, n = 121), and AD (n = 45) participants. The LBD spectrum included Parkinson's disease (PD, n = 32), mild cognitive impairment in PD (PD-MCI, n = 21), and LBD (n = 18) participants. A cognitively unimpaired (CU, n = 39) cohort served as common benchmark. We conducted multivariate analyses of variance and discrimination analyses. Within the AD spectrum, the AD cohort was slower and more inconsistent than the CU, SCI, and MCI cohorts. The MCI cohort was slower than the CU cohort. Within the LBD spectrum, the LBD cohort was slower and more inconsistent than the CU, PD, and PD-MCI cohorts. The PD-MCI cohort was slower than the CU and PD cohorts. In cross-spectra (corresponding cohort) comparisons, the LBD cohort was slower and more inconsistent than the AD cohort. The PD-MCI cohort was slower than the MCI cohort. Discrimination analyses clarified the group difference patterns. For both speed tasks, mean rate and inconsistency demonstrated similar sensitivity to spectra-related comparisons. Both dementia cohorts were slower and more inconsistent than each of their respective non-dementia cohorts.

Brain-targeting autoantibodies in patients with dementia.

Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.1% of dementia patients and in 2.9% of gender-matched controls, with higher frequencies in vascular dementia (42%), Alzheimer's disease (30%), dementia of unknown cause (25%), and subjective cognitive impairment (16.7%). Underlying antigens involved glial fibrillary acidic protein (GFAP), glycine receptor, and Rho GTPase activating protein 26 (ARHGAP26), but also a range of yet undetermined epitopes on neurons, myelinated fiber tracts, choroid plexus, glial cells, and blood vessels. Antibody-positive patients were younger than antibody-negative patients but did not differ in the extent of cognitive impairment, epidemiological and clinical factors, or comorbidities. Further research is needed to understand the potential contribution to disease progression and symptomatology, and to determine the antigenic targets of dementia-associated autoantibodies.

The McCusker Subjective Cognitive Impairment Inventory (McSCI): a novel measure of perceived cognitive decline.

Subjective cognitive decline (SCD), i.e. self/other-reported concerns on one's cognitive functioning without objective evidence of significant decline, is an indicator of dementia risk. There is little consensus on reliability and validity of the available SCD measures. Therefore, introducing a novel and psychometrically sound measure of SCD is timely. The psychometric properties of a new SCD measure, the McCusker Subjective Cognitive Impairment Inventory-Self-Report (McSCI-S), are reported. Through review of previously published measures as well as our clinical and research data on people with SCD, we developed a 46-item self-report questionnaire to assess concerns on six cognitive domains, namely, memory, language, orientation, attention and concentration, visuoconstruction abilities and executive function. The McSCI-S was examined in a cohort of 526 participants using factor analysis, item response theory analysis and receiver operating characteristic (ROC) curve. A unidimensional model provided acceptable fit (CFI = 0.94, TLI = 0.94, RMSEA [90% CI] = 0.052 [.049, 0.055], WRMR = 1.45). The McSCI-S internal consistency was excellent (.96). A cut-off score of ≥24 is proposed to identify participants with SCDs. Higher McSCI-S scores were associated with poorer general cognition, episodic verbal memory, executive function and greater memory complaints and depressive scores (P < .001), controlling for age, sex and education. Excellent reliability and construct validity suggest the McSCI-S estimates SCDs with acceptable accuracy while capturing self-reported concerns for various cognitive domains. The psychometric analysis indicated that this measure can be used in cohort studies as well as on individual, clinical settings to assess SCDs.