Awareness Of Cognitive Decline Research Articles

The natural history of subjective complaints, awareness and metacognition in AD

AbstractBackgroundSubjective cognitive decline (SCD) is the self‐reported experience of decrease in cognitive function in absence of cognitive impairment. This condition is common in elderly subjects and is a frequent reason for referral to memory clinics. SCD is often considered as a stage antedating objective impairment, and an at‐risk condition for subsequent dementia. Recent large‐scale studies, however, support an increased risk only in subjects positive for Alzheimer’s disease (AD) biomarkers, confirming that SCD can be due to multiple mechanisms, including functional cognitive disorders.MethodThis work have reviewed the current research on the awareness of cognitive decline (ACD), with a focus on metacognitive abilities and on assessment tools. The findings from studies of ACD during the course of AD are also reviewed for their possible impact on clinical management.ResultWe propose that, in presence of normal cognitive performance, a subjective overestimation of objective cognitive performance may be a negative prognostic marker, while subjective overestimation of cognitive decline may be compatible with healthy aging or the presence of a functional cognitive disorder.ConclusionLongitudinal studies are needed to test the usefulness of metacognition measures to select SCD subjects for biomarker assessment and/or metacognitive training.

Restless leg syndrome and risk of all-cause dementia: a nationwide retrospective cohort study

BackgroundRestless leg syndrome (RLS) is associated with poor sleep quality, depression or anxiety, poor dietary patterns, microvasculopathy, and hypoxia, all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia remains unclear. This retrospective cohort study aimed to explore the possibility that RLS could be deemed as a non-cognitive prodromal feature of dementia.MethodsThis was a retrospective cohort study using the Korean National Health Insurance Service-Elderly Cohort (aged ≥ 60). The subjects were observed for 12 years, from 2002 to 2013. Identifying patients with RLS and dementia was based on the 10th revised code of the International Classification of Diseases (ICD-10). We compared the risk of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) in 2501 subjects with newly diagnosed RLS and 9977 matched controls based on age, sex, and index date. The association between RLS and the risk of dementia was assessed using Cox regression hazard regression models. The effect of dopamine agonists on the risk of dementia among RLS patients was also explored.ResultsThe baseline mean age was 73.4, and the subjects were predominantly females (63.4%). The incidence of all-cause dementia was higher in the RLS group than that in the control group (10.4% vs 6.2%). A baseline diagnosis of RLS was associated with an increased risk of incident all-cause dementia (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.24–1.72). The risk of developing VaD (aHR 1.81, 95% CI 1.30–2.53) was higher than that of AD (aHR 1.38, 95% CI 1.11–1.72). The use of dopamine agonists was not associated with the risk of subsequent dementia among patients with RLS (aHR 1.00, 95% CI 0.76–1.32).ConclusionsThis retrospective cohort study suggests that RLS is associated with an increased risk of incident all-cause dementia in older adults, providing some evidence that requires confirmation through prospective studies in the future. Awareness of cognitive decline in patients with RLS may have clinical implications for the early detection of dementia.

Differential Patterns of Domain-Specific Cognitive Complaints and Awareness Across the Alzheimer's Disease Spectrum.

Background: Characterizing self- and informant-reported cognitive complaints, as well as awareness of cognitive decline (ACD), is useful for an early diagnosis of Alzheimer’s disease (AD). However, complaints and ACD related to cognitive functions other than memory are poorly studied. Furthermore, it remains unclear which source of information is the most useful to distinguish various groups on the AD spectrum.Methods: Self- and informant-reported complaints were measured with the Everyday Cognition questionnaire (ECog-Subject and ECog-StudyPartner) in four domains (memory, language, visuospatial, and executive). ACD was measured as the subject-informant discrepancy in the four ECog scores. We compared the ECog and ACD scores across cognitive domains between four groups: 71 amyloid-positive individuals with amnestic AD, 191 amnestic mild cognitive impairment (MCI), or 118 cognitively normal (CN), and 211 amyloid-negative CN controls, selected from the ADNI database. Receiver operating characteristic curves analysis was performed to evaluate the accuracy of the ECog and ACD scores in discriminating clinical groups.Results: Self- and informant-reported complaints were generally distributed as follows: memory, language, executive, and visuospatial (from the most severe to the least severe). Both groups of CN participants presented on average more memory and language complaints than their informant. MCI participants showed good agreement with their informants. AD participants presented anosognosia in all domains, but especially for the executive domain. The four ECog-StudyPartner sub-scores allowed excellent discrimination between groups in almost all classifications and performed significantly better than the other two classifiers considered. The ACD was excellent in distinguishing the participants with AD from the two groups of CN participants. The ECog-Subject was the least accurate in discriminating groups in four of the six classifications performed.Conclusion: In research, the study of complaint and anosognosia should not be reduced solely to the memory domain. In clinical practice, non-amnestic complaints could also be linked to Alzheimer’s disease. The presence of an informant also seems necessary given its accuracy as a source of information.

Changes in the awareness of cognitive decline across the course of Alzheimer’s disease: Comparison of two assessment methods

AbstractBackgroundRecent studies have suggested that poor awareness of cognitive decline (ACD) could be an early indicator of Alzheimer's disease (AD). However, there is still no gold‐standard for ACD assessment. In this study, we describe longitudinal changes in ACD in subjects with biomarker‐defined AD (according to the A/T/N framework by Jack and colleagues), assessing ACD by two methods: a subject‐informant discrepancy and a subjective‐objective scores discrepancy.MethodWe included 334 amyloid‐ and tau‐positive (A+T+) subjects with normal cognition, MCI and dementia, and 137 cognitively‐normal A‐T‐ controls from the ADNI cohort, followed up for an average of 5 years. Using a statistical mixed‐effects model (Couronné & al., 2019, ISBI), we reconstructed the evolution of a composite memory score, self and informant’s assessments of cognitive functioning (E‐Cog) and two ACD measures: the ACD index (ACDI, i.e. the difference between E‐Cog‐Subject and E‐Cog‐Informant) and the Meta‐Memory Ratio (MMR, Gagliardi et al. 2019 ART, i.e. the comparison between the E‐Cog‐Subject and a composite memory score). After rescaling the scores, an abnormality threshold was calculated for each of them corresponding to the 95th percentile of the distribution of control subjects.ResultThe subject perceives, at the beginning of the disease, a cognitive decline that is not detected neither by the informant (Figure 1) nor by the tests (Figure 2). This condition can be called "hypernosognosia". The subjective cognitive decline increased slightly and became abnormal 2 years after the diagnosis of dementia. A clear anosognosia was visible starting from the MCI phase using both assessment methods. The MMR detected a reduction in ACD earlier than the ACDI: the subject passes from a hypernosognosia to a good match with the memory score between 64 and 69 years, and with the informant rating between 73 and 76 years on average.ConclusionHypernosognosia is associated with a risk of AD during a short period of time, when the disease is at a very early stage. Thereafter, the individual's ACD decreases. We will discuss the advantages and disadvantages of both assessment methods in both research and clinical practice, especially in relation to their usefulness for early detection of AD.

Awareness of cognitive decline through the continuum of Alzheimer’s disease and its association to APOE‐ε4 and amyloid load

AbstractBackgroundAnosognosia is a common symptom of Alzheimer’s disease (AD) dementia. However, the trajectory of the awareness of cognitive decline (ACD) across the predementia phases remains unclear. This study aimed to outline ACD changes through the entire course of AD, and study the impact of APOE‐ε4 genotype and amyloid load on the ACD evolution.MethodWe included 1280 subjects (7403 visits) from ADNI cohort, aged from 55 to 91 (M=73.7). They are progressors from cognitively‐normal and MCI stages, but also subjects with stable MCI and AD. ACD was measured as the subject‐informant discrepancy on the Everyday cognition (ECog). Using a non‐linear Bayesian mixed‐effects model (Schiratti et al., 2015, NIPS), we recombined the short‐term individual measurements into a long‐term progression of ACD. This allows to map the individual visits onto a common disease timeline, so that the real ages are reparametrized into comparable physiological ages. From each individual trajectory, we extracted the physiological age of (i) maximum hypernosognosia, (ii) accurate awareness, and (iii) anosognosia ‐ whose value corresponded to the upper 20th percentile cut‐off (normalized discrepancy of 0.3). These ages were correlated to the number of ε4 alleles and amyloid status (Aβ+ and Aβ‐) on PET or CSF.ResultAn early phase of hypernosognosia (subject's > informant's ECog) preceded a gradual decrease in ACD, eventually leading to a clear anosognosia (Figure 1, with 100 bootstrapped runs). Unawareness started on average 5 years before diagnosis. APOE‐ε4 carriers reached the peak of hypernosognosia and the anosognosia cut‐off earlier than the non‐carriers (all p<.001; Figure 2). Aβ+ subjects reached the peak of hypernosognosia later than Aβ‐, but their ACD started to decline earlier (all p<.05; Figure 3).ConclusionThe role of cognitive complaints and low ACD in AD is currently highly debated. Our study showed that both are associated with AD pathology, being two conditions that occur in temporal succession. This has strong implications in terms of timely and accurate diagnosis, and in patients’ treatment. Further analyses may study the longitudinal trajectory of ACD in relation to additional AD features, such as brain atrophy and metabolism, especially in the predementia phases.

Reduced awareness of cognitive decline is associated with brain amyloid load in asymptomatic elderly individuals at risk for AD: A longitudinal study

AbstractBackgroundIt has recently been proposed that the awareness of cognitive decline (ACD) may already be slightly reduced in the preclinical phase of AD, in the presence of subtle cognitive changes. This is a recent field of research, and the few studies available do not allow to appreciate the actual evolution of ACD in the pre‐dementia phases of AD. The present study describes the longitudinal trajectory of an index of ACD (ACDI) over 3 years in a cohort of cognitively‐normal elderly, its association to AD biomarkers, as well as its impact on cognitive scores’ evolution.Method314 elderly memory complainers, as just as many study‐partners, were followed‐up for 3 years. Brain glucose metabolism and amyloid load were assessed at baseline; screening cognitive tests were performed every 6 months, and a comprehensive neuropsychological evaluation every 12 months. The ACDI was based on the subject‐informant discrepancy on a questionnaire evaluating the subject’s cognitive decline. We performed a Latent Class Linear Mixed Model (LCLMM) to identify different trends of evolution of the ACDI over time, and Generalized Linear Mixed Models to analyse the impact of the baseline ACDI on the evolution of cognitive scores.ResultThe LCLMM identified three classes of subjects sharing similar longitudinal trajectories of the ACDI. Most subjects (76.8%) have accurate ACD (Class 2), and have been considered as the reference group. 18.95% of subjects showed heightened ACD (“worried‐well” individuals). They were comparable to subjects with accurate ACD in terms of AD biomarkers. 4.25% of the sample showing low ACD had higher amyloid burden than the reference group, and were mostly men. The GLMM found no overall effect of baseline ACDI on the evolution of the cognitive scores.ConclusionThe study of ACD in AD, its evolution and correlates is a topic of growing interest, as it is, notably, a piece of the larger understanding of the pre‐dementia phases of AD. This can be useful for a timely diagnosis of AD, and for the selection of populations to be included in clinical trials.

Awareness of cognitive decline and CSF‐biomarkers in memory clinic patients: Results from the DELCODE‐study

AbstractBackgroundDecreased awareness of cognitive deficits is a common symptom of dementia. Less is known about the evolution of decreased awareness in earlier stages of Alzheimer’s Disease (AD). Recent studies using the discrepancy between self‐ and informant report found reduced awareness in many patients with mild cognitive impairment (MCI), but generally heightened awareness in cognitively normal individuals with Amyloid pathology. In memory clinic samples, patient and caregiver ratings of cognitive decline were associated with AD‐biomarkers. We investigated in the relationship between CSF‐biomarkers, informant ratings and reduced self‐awareness in a large memory‐clinic sample.MethodsWe analyzed data from n=323 patients with available CSF‐biomarkers (age=71.17; SD=5.71) from the DELCODE‐study (n=211 SCD‐patients; n=112 MCI‐patients). Cognitive complaints in five different domains were assessed using a self‐ and informant rated interview form (Miebach et al. 2019). Reduced self‐awareness was calculated using a self‐/informant discrepancy score. The relationship with CSF‐biomarker was examined using linear regression, controlling for demographic variables and objective memory performance. Participants were classified using the ATN‐system for the diagnosis of preclinical AD.ResultsAll patients reported a cognitive decline in at least 3 domains. On average, SCD participants had positive self‐awareness scores (M=1.20; SD=1.87), indicating more self‐ than informant reported decline, while this significantly reversed in MCI (M=‐.514; SD=1.67). In the total sample, the discrepancy was associated with CSF‐Aß‐42 (ß=.213; p<.000), CSF‐t‐Tau (ß=‐.163; p<.005) and CSF‐Aß/tau‐ratio (ß=.232; p<.001). This association was similar in SCD and MCI. Regarding Biomarker profiles, n=66 participants were classified as A+/T+, n=38 as A+/T‐; n=139 participants were classified as A‐T‐N‐ and n=80 as non‐AD‐pathologic change. Participants with an AD‐typical Biomarker profile (A+/T+) had significantly higher informant than self‐ratings of cognitive decline (p<.001) and reduced awareness (p<.003).ConclusionIn memory clinic patients, lower awareness (i.e. relatively less self‐ than informant rated complaints) was associated with CSF‐Aß‐42, t‐Tau and the Aß/tau‐ratio. The relationship with CSF‐Aß42 and Aß/tau ratio was independent from objective memory impairment, showing that in the absence of objective impairment (i.e. SCD stage) informant ratings of cognitive decline are particularly informative. Results support the use of informant ratings in memory clinic samples, and the inclusion of an informant confirmation in the SCD‐plus criteria, specifying which features increase the likelihood of AD‐pathology in SCD.

Awareness of cognitive decline trajectories in asymptomatic individuals at risk for AD

BackgroundLack of awareness of cognitive decline (ACD) is common in late-stage Alzheimer’s disease (AD). Recent studies showed that ACD can also be reduced in the early stages.MethodsWe described different trends of evolution of ACD over 3 years in a cohort of memory-complainers and their association to amyloid burden and brain metabolism. We studied the impact of ACD at baseline on cognitive scores’ evolution and the association between longitudinal changes in ACD and in cognitive score.Results76.8% of subjects constantly had an accurate ACD (reference class). 18.95% showed a steadily heightened ACD and were comparable to those with accurate ACD in terms of demographic characteristics and AD biomarkers. 4.25% constantly showed low ACD, had significantly higher amyloid burden than the reference class, and were mostly men. We found no overall effect of baseline ACD on cognitive scores’ evolution and no association between longitudinal changes in ACD and in cognitive scores.ConclusionsACD begins to decrease during the preclinical phase in a group of individuals, who are of great interest and need to be further characterized.Trial registrationThe present study was conducted as part of the INSIGHT-PreAD study. The identification number of INSIGHT-PreAD study (ID-RCB) is 2012-A01731-42.

The meta-memory ratio: a new cohort-independent way to measure cognitive awareness in asymptomatic individuals at risk for Alzheimer\u2019s disease

BackgroundLack of awareness of cognitive decline (ACD) has been described at the preclinical and prodromal stages of Alzheimer’s disease (AD). In this study, we introduced a meta-memory ratio (MMR) and explored how it is associated with neuroimaging AD biomarkers in asymptomatic individuals at risk for AD.MethodFour hundred forty-eight cognitively healthy participants from two cohorts of subjective memory complainers (INSIGHT-PreAD and ADNI) were included. Regression models were used to assess the impact of AD biomarkers on the MMR.ResultIn both cohorts, there was a significant quadratic effect of cerebral amyloidosis on the MMR value. In particular, participants had a high ACD up to the amyloid positivity threshold, above which a decrease of ACD was eventually observed as the amyloid load increased.ConclusionThis nonlinear evolution of ACD in very early AD must be taken into account in clinical care and for trial enrollment as well.

P2‐465: DIFFERENTIAL PATTERNS OF DOMAIN‐SPECIFIC NOSOGNOSIA ACROSS THE ALZHEIMER'S DISEASE SPECTRUM

While anosognosia is common in patients with Alzheimer's disease (AD), there is a lack of consensus regarding the awareness of cognitive decline in earlier stages of the disease. Furthermore, studies of anosognosia in these populations have largely focussed on global disease awareness or memory symptoms awareness. Therefore, the aim of this study was to assess patterns of nosognosia in various cognitive domains across the complete AD spectrum. A total of 817 subjects (178 cognitively normal, 96 significant memory concern (SMC), 274 early MCI (E-MCI), 146 late MCI (L-MCI) and 123 AD) from the ADNI database was included. The Everyday Cognition (Ecog) questionnaire was administered to all subjects as well as to their study partners. This tool evaluates the decrease of performance in six cognitive domains (memory, language, visuospatial, planning, organization and attention) over the last ten years. A mixed ANOVA was conducted to identify cognitive domains in which subjects and study partner's ratings of performance changes were significantly different, in each group. Then, in groups in which anosognosia was found, we computed and compared domain-specific nosognosia scores (difference between the partner rating and the subject rating) to identify cognitive domains in which anosognosia was more important. CTRL, SMC and E-MCI patients reported significantly more decreases in performance on most cognitive domains, in comparison to their study partners. L-MCI patients reported significantly less decreases in performance regarding their executive functioning (organization and planning). Finally, AD patients reported less decreases in performance on all cognitive domains, although anosognosia for language was significantly lower in comparison to all other cognitive domains (even when only considering patients with language impairments according to the study partner). This study unveils the evolution of nosognosia on the AD spectrum, from hypernosognosia presented in CTRL, SMC and E-MCI, to the mild domain-specific anosognosia presented in L-MCI and finally, the more severe global anosognosia in AD patients. Awareness for decline in language seems to be better preserved in AD patients, relatively to other domains. These results have important clinical implications, since it has been shown that nosognosia can impact the reliability of symptoms’ self-report, risk-taking behaviors and caregiver burden.

CLINICAL PREDICTORS OF SOMATIC AND PSYCHOLOGICAL SYMPTOMS OF DEPRESSION IN ALZHEIMER'S DISEASE

The Hamilton Rating Scale for Depression was employed to assess the severity of somatic and psychological symptoms of depression in 42 outpatients with dementia of the Alzheimer type. The severity of somatic symptoms increased in the more severe stages of dementia whereas the severity of psychological symptoms did not vary. Psychological symptoms were more severe in female patients and in patients with a better awareness of cognitive decline. In contrast, the degree of cognitive dysfunction was the only significant predictor of the severity of somatic symptoms. These results suggest that, in Alzheimer's disease, somatic symptoms are secondary to dementia rather than manifestations of a coexistent depressive disorder and point to the limited value of the Hamilton scale for detecting depression in demented patients.