Inferior Frontal Sulcal Hyperintensities on Brain MRI Are Associated with Amyloid Positivity beyond Age-Results from the Multicentre Observational DELCODE Study.

Inferior frontal sulcal hyperintensities (IFSHs) on fluid-attenuated inversion recovery (FLAIR) sequences have been proposed to be indicative of glymphatic dysfunction. Replication studies in large and diverse samples are nonetheless needed to confirm them as an imaging biomarker. We investigated whether IFSHs were tied to Alzheimer's disease (AD) pathology and cognitive performance. We used data from 361 participants along the AD continuum, who were enrolled in the multicentre DELCODE study. The IFSHs were rated visually based on FLAIR magnetic resonance imaging. We performed ordinal regression to examine the relationship between the IFSHs and cerebrospinal fluid-derived amyloid positivity and tau positivity (Aß42/40 ratio ≤ 0.08; pTau181 ≥ 73.65 pg/mL) and linear regression to examine the relationship between cognitive performance (i.e., Mini-Mental State Examination and global cognitive and domain-specific performance) and the IFSHs. We controlled the models for age, sex, years of education, and history of hypertension. The IFSH scores were higher in those participants with amyloid positivity (OR: 1.95, 95% CI: 1.05-3.59) but not tau positivity (OR: 1.12, 95% CI: 0.57-2.18). The IFSH scores were higher in older participants (OR: 1.05, 95% CI: 1.00-1.10) and lower in males compared to females (OR: 0.44, 95% CI: 0.26-0.76). We did not find sufficient evidence linking the IFSH scores with cognitive performance after correcting for demographics and AD biomarker positivity. IFSHs may reflect the aberrant accumulation of amyloid ß beyond age.

Fornix fractional anisotropy mediates the association between Mediterranean diet adherence and memory four years later in older adults without dementia.

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 ± 6.09 years; 48.7 % female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memory's mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95 % confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95 % CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.

Fronto-striatal alterations correlate with apathy severity in behavioral variant frontotemporal dementia.

Structural and functional changes in cortical and subcortical regions have been reported in behavioral variant frontotemporal dementia (bvFTD), however, a multimodal approach may provide deeper insights into the neural correlates of neuropsychiatric symptoms. In this multicenter study, we measured cortical thickness (CTh) and subcortical volumes to identify structural abnormalities in 37 bvFTD patients, and 37 age- and sex-matched healthy controls. For seed regions with significant structural changes, whole-brain functional connectivity (FC) was examined in a sub-cohort of N = 22 bvFTD and N = 22 matched control subjects to detect complementary alterations in brain network organization. To explore the functional significance of the observed structural and functional deviations, correlations with clinical and neuropsychological outcomes were tested where available. Significantly decreased CTh was observed in the bvFTD group in caudal middle frontal gyrus, left pars opercularis, bilateral superior frontal and bilateral middle temporal gyrus along with subcortical volume reductions in bilateral basal ganglia, thalamus, hippocampus, and amygdala. Resting-state functional magnetic resonance imaging showed decreased FC in bvFTD between: dorsal striatum and left caudal middle frontal gyrus; putamen and fronto-parietal regions; pallidum and cerebellum. Conversely, bvFTD showed increased FC between: left middle temporal gyrus and paracingulate gyrus; caudate nucleus and insula; amygdala and parahippocampal gyrus. Additionally, cortical thickness in caudal, lateral and superior frontal regions as well as caudate nucleus volume correlated negatively with apathy severity scores of the Neuropsychiatry Inventory Questionnaire. In conclusion, multimodal structural and functional imaging indicates that fronto-striatal regions have a considerable influence on the severity of apathy in bvFTD.

Cognitive Trajectories in Preclinical and Prodromal Alzheimer's Disease Related to Amyloid Status and Brain Atrophy: A Bayesian Approach.

Background: Cognitive decline is a key outcome of clinical studies in Alzheimer's disease (AD). Objective: To determine effects of global amyloid load as well as hippocampus and basal forebrain volumes on longitudinal rates and practice effects from repeated testing of domain specific cognitive change in the AD spectrum, considering non-linear effects and heterogeneity across cohorts. Methods: We included 1,514 cases from three cohorts, ADNI, AIBL, and DELCODE, spanning the range from cognitively normal people to people with subjective cognitive decline and mild cognitive impairment (MCI). We used generalized Bayesian mixed effects analysis of linear and polynomial models of amyloid and volume effects in time. Robustness of effects across cohorts was determined using Bayesian random effects meta-analysis. Results: We found a consistent effect of amyloid and hippocampus volume, but not of basal forebrain volume, on rates of memory change across the three cohorts in the meta-analysis. Effects for amyloid and volumetric markers on executive function were more heterogeneous. We found practice effects in memory and executive performance in amyloid negative cognitively normal controls and MCI cases, but only to a smaller degree in amyloid positive controls and not at all in amyloid positive MCI cases. Conclusions: We found heterogeneity between cohorts, particularly in effects on executive functions. Initial increases in cognitive performance in amyloid negative, but not in amyloid positive MCI cases and controls may reflect practice effects from repeated testing that are lost with higher levels of cerebral amyloid.

Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline.

BACKGROUND AND OBJECTIVES: To determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer disease (AD) biomarkers, cognitive decline, and clinical progression to mild cognitive impairment (MCI). METHODS: This study included patients with clinical SCD and SCD-free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-ß (Aß)42/Aß40, phosphorylated tau (p-tau181), total tau and Aß42/p-tau181 levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up M ± SD: 40.6 ± 23.7 months). In addition, we explored group differences between SCD and HC in those without MNPD. RESULTS: In our sample (N = 672, mean age: 70.7 ± 5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline, and a higher risk of progression to incident MCI (HR: 4.07, 95% CI 2.46-6.74) compared with SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95% CI 38.5-75.4) and a negative predictive value of 86.0% (95% CI 81.9-90.1) for the progression of SCD to MCI within 3 years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared with HC participants without MNPD (n = 215; HR: 4.09, 95% CI 2.07-8.09), while AD biomarker levels did not differ significantly between these groups. DISCUSSION: Our results suggest that MNPD are a risk factor for AD-related clinical progression in cognitively normal patients seeking medical counseling because of SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD.

Linking early-life bilingualism and cognitive advantage in older adulthood.

Previous studies have identified bilingualism as a protective factor against dementia. Here we aimed to test whether being bilingual at different life stages impacts cognition and brain structure in older adulthood. We included 746 participants from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Assessment of bilingualism at 3 life stages (early: 13-30, middle: 30-65 and late: over 65 years old) was determined with the Lifetime of Experiences Questionnaire. Individuals reporting bilingualism (i.e., daily use of L2) in the early life stage outperformed monolinguals on learning & memory, working-memory, executive functions and language. Bilingualism in middle life stage showed a significant advantage on learning & memory, while no effect of bilingualism in old life stage was identified. Brain gray matter volume was not associated with L2 use and did not differ between groups. However, stronger correlations between brain gray matter volume in selected brain regions and cognitive performance were found in bilingual participants in the early and middle life stages. Our results indicate that bilingualism in early life might provide a long-lasting protective effect on cognition and shape the brain to sustain cognitive performance in older adulthood.

Lifelong experiences as a proxy of cognitive reserve moderate the association between connectivity and cognition in Alzheimer's disease.

Alzheimer's disease (AD) is associated with alterations in functional connectivity (FC) of the brain. The FC underpinnings of CR, that is, lifelong experiences, are largely unknown. Resting-state FC and structural MRI were performed in 76 CSF amyloid-ß (Aß) negative healthy controls and 152 Aß positive individuals as an AD spectrum cohort (ADS; 55 with subjective cognitive decline, SCD; 52 with mild cognitive impairment; 45 with AD dementia). Following a region-of-interest (ROI) FC analysis, intrinsic network connectivity within the default-mode network (INC-DMN) and anti-correlation in INC between the DMN and dorsal attention network (DMN:DAN) were obtained as composite scores. CR was estimated by education and Lifetime Experiences Questionnaire (LEQ). The association between INC-DMN and MEM was attenuated by higher LEQ scores in the entire ADS group, particularly in SCD. In ROI analyses, higher LEQ scores were associated with higher FC within the DMN in ADS group. INC-DMN remains relatively intact despite memory decline in individuals with higher lifetime activity estimates, supporting a role for functional networks in maintaining cognitive function in AD.

Musical Activity During Life Is Associated With Multi-Domain Cognitive and Brain Benefits in Older Adults.

Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer's disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults (OA) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Participants reporting having played a musical instrument across three life periods (n = 70) were compared to controls without a history of musical instrument playing (n = 70), well-matched for reserve proxies of education, intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion.

Mediterranean Diet, Alzheimer Disease Biomarkers and Brain Atrophy in Old Age.

OBJECTIVE: To determine if following a Mediterranean-like diet (MeDi) relates to cognitive functions and in vivo biomarkers for Alzheimer's disease (AD), we analyzed cross-sectional data from the German Longitudinal Cognitive Impairment and Dementia Study METHOD: The sample (n=512, mean age: 69.5±5.9 years) included 169 cognitively normal participants and subjects at higher AD risk (53 AD relatives, 209 SCD and 81 MCI). We defined MeDi adherence based on the Food Frequency Questionnaire. Brain volume outcomes were generated via voxel-based morphometry on T1-MRI and cognitive performance with an extensive neuropsychological battery. AD-related biomarkers (Aß42/40 ratio, pTau181) in cerebrospinal fluid were assessed in n=226 individuals. We analyzed the associations between MeDi and the outcomes with linear regression models controlling for several covariates. Additionally, we applied hypothesis-driven mediation and moderation analysis. RESULTS: Higher MeDi adherence related to larger mediotemporal gray matter volume (p<0.05 FWE corrected), better memory (ß±SE = 0.03 ± 0.02; p=0.038), and less amyloid (Aß42/40 ratio, ß±SE = 0.003 ± 0.001; p=0.008) and pTau181 pathology (ß±SE = -1.96±0.68; p=0.004). Mediotemporal volume mediated the association between MeDi and memory (40% indirect mediation). Finally, MeDi favorably moderated the associations between Aß42/40 ratio, pTau181 and mediotemporal atrophy. Results were consistent correcting for ApoE-ε4 status. CONCLUSION: Our findings corroborate the view of MeDi as a protective factor against memory decline and mediotemporal atrophy. Importantly, they suggest that these associations might be explained by a decrease of amyloidosis and tau-pathology. Longitudinal and dietary intervention studies should further examine this conjecture and its treatment implications.

Minor neuropsychological deficits in patients with subjective cognitive decline.

OBJECTIVE: To determine the nature and extent of minor neuropsychological deficits in patients with subjective cognitive decline (SCD) and their association with CSF biomarkers of Alzheimer disease (AD). METHOD: We analyzed data from n = 449 cognitively normal participants (n = 209 healthy controls, n = 240 patients with SCD) from an interim data release of the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE). An extensive neuropsychological test battery was applied at baseline for which we established a latent, 5 cognitive domain factor structure comprising learning and memory, executive functions, language abilities, working memory, and visuospatial functions. We compared groups in terms of global and domain-specific performance and correlated performance with different CSF markers of AD pathology. RESULTS: We observed worse performance (Cohen d = ≈0.25-0.5, adjusted for age, sex differences with analysis of covariance) in global performance, memory, executive functions, and language abilities for the SCD group compared to healthy controls. In addition, worse performance in these domains was moderately (r = ≈0.3) associated with lower CSF ß-amyloid42/40 and CSF ß-amyloid42/phosphorylated tau181 in the whole sample and specifically in the SCD subgroup. CONCLUSIONS: Within the spectrum of clinically unimpaired (i.e., before mild cognitive impairment) cognitive performance, SCD is associated with minor deficits in memory, executive function, and language abilities. The association of these subtle cognitive deficits with AD CSF biomarkers speaks to their validity and potential use for the early detection of underlying preclinical AD.

Multimodal MRI analysis of basal forebrain structure and function across the Alzheimer's disease spectrum.

BACKGROUND: Dysfunction of the cholinergic basal forebrain (cBF) is associated with cognitive decline in Alzheimer's disease (AD). Multimodal MRI allows for the investigation of cBF changes in-vivo. In this study we assessed alterations in cBF functional connectivity (FC), mean diffusivity (MD), and volume across the spectrum of AD. We further assessed effects of amyloid pathology on these changes. METHODS: Participants included healthy controls, and subjects with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or AD dementia (ADD) from the multicenter DELCODE study. Resting-state functional MRI (rs-fMRI) and structural MRI data was available for 477 subjects, and a subset of 243 subjects also had DTI data available. Differences between diagnostic groups were investigated using seed-based FC, volumetric, and MD analyses of functionally defined anterior (a-cBF) and posterior (p-cBF) subdivisions of a cytoarchitectonic cBF region-of-interest. In complementary analyses groups were stratified according to amyloid status based on CSF Aß42/40 biomarker data, which was available in a subset of participants. RESULTS: a-cBF and p-cBF subdivisions showed regional FC profiles that were highly consistent with previously reported patterns, but there were only minimal differences between diagnostic groups. Compared to controls, cBF volumes and MD were significantly different in MCI and ADD but not in SCD. The Aß42/40 stratified analyses largely matched these results. CONCLUSIONS: We reproduced subregion-specific FC profiles of the cBF in a clinical sample spanning the AD spectrum. At least in this multicentric cohort study, cBF-FC did not show marked changes along the AD spectrum, and multimodal MRI did not provide more sensitive measures of AD-related cBF changes compared to volumetry.

Antisaccade and prosaccade eye movements in individuals clinically at risk for psychosis: comparison with first-episode schizophrenia and prediction of conversion.

Saccadic eye movements are well-described markers of cerebral function and have been widely studied in schizophrenia spectrum populations. However, less is known about saccades in individuals clinically at risk for schizophrenia. Therefore, we studied individuals in an at-risk mental state (ARMS) (N = 160), patients in their first episode of schizophrenia (N = 32) and healthy controls (N = 75). N = 88 ARMS participants showed an early at-risk mental state (E-ARMS), defined by cognitive-perceptive basic symptoms (COPER) or a combination of risk and loss of function, whereas N = 72 were in a late at-risk mental state (L-ARMS), defined by attenuated psychotic symptoms or brief limited intermittent psychotic symptoms. We examined prosaccades, reflecting overt attentional shifts, and antisaccades, measuring inhibitory control, as well as their relationship as an indicator of the interplay of bottom-up and top-down influences. L-ARMS but not E-ARMS participants had increased antisaccade latencies compared to controls. First-episode patients had higher antisaccade error rates compared to E-ARMS participants and controls, and increased latencies compared to all other groups. Prosaccade latencies did not differ between groups. We observed the expected negative correlation between prosaccade latency and antisaccade error rate, indicating that individuals with shorter prosaccade latencies made more antisaccade errors. The magnitude of the association did not differ between groups. No saccadic measure predicted conversion to psychosis within 2 years. These findings confirm the existence of antisaccade impairments in patients with schizophrenia and provide evidence that volitional response generation in the antisaccade task may be affected even before onset of clinically overt psychosis.

Cognitive Complaints in Memory Clinic Patients and in Depressive Patients: An Interpretative Phenomenological Analysis.

BACKGROUND AND OBJECTIVES: Cognitive complaints are discussed as early signs of Alzheimer's disease (AD). However, they are also very common in cognitively normal older adults and in patients with depression. Qualitative, interview-based approaches might be useful to identify those features of cognitive complaints specific for the experiences of cognitive decline in preclinical or prodromal AD versus those complaints typically reported by depressed patients. RESEARCH DESIGN AND METHODS: A semi-structured interview was administered to 21 cognitively normal older adults (HC), 18 nondemented memory clinic patients (MC), and 11 patients with a major depression (MD), all above 55 years. Interpretative phenomenological analysis (IPA) was applied to the interview transcripts to develop emerging complaint themes in each group. To identify thematic correspondence and possibly novel, hitherto unappreciated themes, the extracted complaint categories were compared with the neurocognitive domains in the DSM-5 and the content of the Everyday Cognition questionnaire (E-Cog). RESULTS: IPA yielded 18 cognitive complaint categories in MC, 10 in depressive patients, and 10 categories in the HC group. Several themes were common across groups, but some were group-specific, for example, spatial disorientation was only reported in MC patients. Some of these MC-specific themes were neither represented by DSM-5 domains nor by the E-Cog. DISCUSSION AND IMPLICATIONS: We report a comprehensive qualitative description of cognitive complaints in old age which could help to develop questionnaires or structured interviews to better assess AD-related subjective cognitive decline. This may help to increase specificity in selecting high-risk subjects in research settings and improve clinical judgment of diverse cognitive complaints types mentioned by their patients.

Selective attention to smoking cues in former smokers.

Repeated drug use modifies the emotional and cognitive processing of drug-associated cues. These changes are supposed to persist even after prolonged abstinence. Several studies demonstrated that smoking cues selectively attract the attention of smokers, but empirical evidence for such an attentional bias among successful quitters is inconclusive. Here, we investigated whether attentional biases persist after smoking cessation. Thirty-eight former smokers, 34 current smokers, and 29 non-smokers participated in a single experimental session. We used three measures of attentional bias for smoking stimuli: A visual probe task with short (500ms) and long (2000ms) picture stimulus durations, and a modified Stroop task with smoking-related and neutral words. Former smokers and current smokers, as compared to non-smokers, showed an attentional bias in visual orienting to smoking pictures in the 500ms condition of the visual probe task. The Stroop interference index of smoking words was negatively related to nicotine dependence in current smokers. Former smokers and mildly dependent smokers, as compared to non-smokers, showed increased interference by smoking words in the Stroop task. Neither current nor former smokers showed an attentional bias in maintained attention (2000ms visual probe task). In conclusion, even after prolonged abstinence smoking cues retain incentive salience in former smokers, who differed from non-smokers on two attentional bias indices. Attentional biases in former smokers operate mainly in early involuntary rather than in controlled processing, and may represent a vulnerability factor for relapse. Therefore, smoking cessation programs should strengthen self-control abilities to prevent relapses.

Different Cognitive Complaint Profiles in Memory Clinic and Depressive Patients.

OBJECTIVE: Cognitive complaints are considered early indicators of incipient Alzheimer's disease (AD) but are very common in geriatric patients, especially in patients with major depressive disorder (MDD). The clinical assessment of cognitive complaints is still poorly operationalized. Recent qualitative research suggests that certain phenomenologic complaint themes may have some specificity for prodromal AD. The aim of the study was to replicate and explore their occurrence in a clinical setting. METHODS: In a cross-sectional, case-control study using a mixed-methods approach, 23 memory clinic (cognitive complainers [CC]) patients, 21 psychiatric inpatients with MDD, and 21 healthy control subjects, aged 55-86 years, were assessed at the Department of Psychiatry and Psychotherapy and German Center for Neurodegenerative Diseases, Bonn. A newly developed semistructured interview addressing 12 complaint themes was used, and transcribed open format responses were coded by qualitative expert rating (theme absent versus present) and compared between the groups. RESULTS: Seven complaint themes (e.g., sense of predomination, progression) were significantly more often endorsed by the CC group, together with a novel theme of "distractible speech." Complaint themes in those with depression aligned with the depressive symptoms and appeared to be partly different from the complaint pattern of the CC group. CONCLUSION: Previously established themes were found to be feasible for conversion into a semistructured interview. Several complaint phenotypes were confirmed and previous themes significantly expanded by providing first evidence for a qualitatively different complaint profile in MDD compared with CC. Future investigations may benefit from better characterizing the phenomenologic and qualitative characteristics of AD-related complaints.

Face-Name Associative Recognition Deficits in Subjective Cognitive Decline and Mild Cognitive Impairment.

BACKGROUND: There is a need for more sensitive neuropsychological tests to detect subtle cognitive deficits emerging in the preclinical stage of Alzheimer's disease (AD). Associative memory is a cognitive function supported by the hippocampus and affected early in the process of AD. OBJECTIVE: We developed a short computerized face-name associative recognition test (FNART) and tested whether it would detect memory impairment in memory clinic patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). METHODS: We recruited 61 elderly patients with either SCD (n = 32) or MCI (n = 29) and 28 healthy controls (HC) and compared performance on FNART, self-reported cognitive deterioration in different domains (ECog-39), and, in a reduced sample (n = 46), performance on the visual Paired Associates Learning of the CANTAB battery. RESULTS: A significant effect of group on FNART test performance in the total sample was found (p < 0.001). Planned contrasts indicated a significantly lower associative memory performance in the SCD (p = 0.001, d = 0.82) and MCI group (p < 0.001, d = 1.54), as compared to HCs, respectively. The CANTAB-PAL discriminated only between HC and MCI, possibly because of reduced statistical power. Adjusted for depression, performance on FNART was significantly related to ECog-39 Memory in SCD patients (p = 0.024) but not in MCI patients. CONCLUSIONS: Associative memory is substantially impaired in memory clinic patients with SCD and correlates specifically with memory complaints at this putative preclinical stage of AD. Further studies will need to examine the predictive validity of the FNART in SCD patients with regard to longitudinal (i.e., conversion to MCI/AD) and biomarker outcomes.

Subjective Cognitive Decline from a Phenomenological Perspective: A Review of the Qualitative Literature.

BACKGROUND: Subjective cognitive decline is related to greater risk of dementia and biological markers of Alzheimer's disease (AD), but researchers are yet to characterize the phenomenological perspective of cognitive decline in those with and without a diagnosis of AD. OBJECTIVE: To collate and synthesize studies measuring the subjective experience of cognitive change or decline in healthy older adults and those with mild cognitive impairment and AD. METHODS: We reviewed 58 peer-reviewed articles that were found to directly or indirectly refer to the subjective experience of cognitive decline. RESULTS: We extracted eight central themes, dealing with cognitive changes experienced by each diagnostic group, and also related to issues of changing self-identity, the causal attribution of cognitive decline, the anxiety and concern related to perceived decline, the negative perceptions attached to a diagnosis of dementia, changing levels of insight, and perception of well-being in aging. CONCLUSION: This review is the first step toward characterizing phenomenological profiles of cognitive change in both non-demented and demented older adults. Developing a clearer understanding of subjective cognitive decline, particularly at the earliest stages of AD, will augment the sensitivity of detection of individuals at greater risk of future dementia.

Feature Binding Deficits in Subjective Cognitive Decline and in Mild Cognitive Impairment.

BACKGROUND: Feature binding is a sensitive and specific cognitive marker for Alzheimer's disease (AD). Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are clinical categories associated with an increased risk for AD. OBJECTIVE: To investigate whether the SCD and MCI group are impaired with regard to feature binding. METHODS: The feature binding test was administered to memory clinic patients with either SCD (n = 19, mean MMSE: 29.2) or with MCI (n = 23, mean MMSE: 26.5), and to a group of healthy controls (HC, n = 23, mean MMSE: 29.0). Participants were assessed with the CERAD Plus neuropsychological test battery. Cognitive performance of the three groups was compared by ANCOVA with age, gender and education as covariates and planned contrasts. RESULTS: Groups differed in the binding condition. Planned contrasts showed significant differences in adjusted means between HC and SCD (p = 0.003), as well as between HC and MCI (p <  0.0001). DISCUSSION: The feature binding task detects subtle cognitive impairments in participants with SCD, who are unimpaired in traditional neuropsychological testing. This corroborates the use of feature binding tests in preclinical AD studies and suggests that specific cognitive deficits can be found in SCD. Future studies incorporating AD biomarkers and longitudinal follow-up are needed to further establish the clinical utility of feature binding.

[Neuropsychological Functioning as a Predictor of Treatment Response to Psychoeducational, Cognitive Behavioral Therapy in People at Clinical High Risk of First Episode Psychosis]. / Neuropsychologische Funktionen als Prädiktoren des Therapieerfolgs von psychoedukativer, kognitiv verhaltenstherapeutischer Therapie bei Personen mit erhöhtem Psychoserisiko.

OBJECTIVE: Investigate whether treatment response in people at clinical high risk of psychosis (CHR) is predicted by their cognitive performance. METHOD: 128 CHR outpatients were randomized into two treatment groups, one receiving integrated psychological intervention (IPI), including psychoeducation, the other receiving supportive counselling (SC) for 12 months. Multiple regression analysis was used to identify neurocognitive predictors of treatment response in a subgroup of n = 105, measured by symptomatic and functional improvement at 1-year follow-up. RESULTS: In the IPI, treatment response was associated with performance of executive control and processing speed (R²â€Š= 0.27, p = 0.002). In both treatment groups, performance of working memory/attention was a significant predictor (IPI: R²â€Š= 0.15, p = 0.039, SC: R²â€Š= 0.19, p = 0.012). CONCLUSION: Cognitive performance is associated with treatment response in CHR people. The enhancement of cognitive performance is a useful target of early intervention.

Predisposing and precipitating factors of delirium after cardiac surgery: a prospective observational cohort study.

OBJECTIVE: To comprehensively assess pre-, intra-, and postoperative delirium risk factors as potential targets for intervention. BACKGROUND: Delirium after cardiac surgery is associated with longer intensive care unit (ICU) stay, and poorer functional and cognitive outcomes. Reports on delirium risk factors so far did not cover the full range of patients' presurgical conditions, intraoperative factors, and postoperative course. METHODS: After written informed consent, 221 consecutive patients ≥ 50 years scheduled for cardiac surgery were assessed for preoperative cognitive performance, and functional and physical status. Clinical and biochemical data were systematically recorded perioperatively. RESULTS: Of the 215 patients remaining for analysis, 31% developed delirium in the intensive care unit. Using logistic regression models, older age [73.3 (71.2-75.4) vs 68.5 (67.0-70.0); P = 0.016], higher Charlson's comorbidity index [3.0 (1.5-4.0) vs 2.0 (1.0-3.0) points; P = 0.009], lower Mini-Mental State Examination (MMSE) score (MMSE, [27 (23-29) vs 28 (27-30) points; P = 0.021], length of cardiopulmonary bypass (CPB) [CPB; 133 (112-163) vs 119 (99-143) min; P = 0.004], and systemic inflammatory response syndrome in the intensive care unit [25 (36.2%) vs 13 (8.9%); P = 0.001] were independently associated with delirium. Combining age, MMSE score, Charlson's comorbidity index, and length of CPB in a regression equation allowed for a prediction of postoperative delirium with a sensitivity of 71.19% and a specificity of 76.26% (receiver operating analysis, area under the curve: 0.791; 95% confidence interval: 0.727-0.845). CONCLUSIONS: Further research will evaluate if modification of these risk factors prevents delirium and improves outcomes.