Cedrés, Nira

Abstract Background Subjective cognitive decline (SCD) has gained recent interest as a potential harbinger of neurodegenerative diseases such as Alzheimer’s disease (AD) and cerebrovascular disease (CVD). In addition, SCD can be related to depressive symptomatology. However, the association between AD and CVD biomarkers, depressive symptomatology, and SCD is still unclear. We investigated the association of AD and CVD biomarkers and depressive symptomatology with SCD in individuals with subjective memory complaints (SCD-memory group) and individuals with subjective concentration complaints (SCD-concentration group). Methods We recruited a population-based cohort of 217 individuals (all aged 70 years, 53% female participants, 119 SCD-memory individuals, 23 SCD-concentration individuals, and 89 controls). AD and CVD were assessed through cerebrospinal fluid levels of the Aβ42/40 ratio and phosphorylated tau, and white matter signal abnormalities on magnetic resonance imaging, respectively. Associations between biomarkers, depressive symptomatology, and SCD were tested via logistic regression and correlation analyses. Results We found a significant association between depressive symptomatology with SCD-memory and SCD-concentration. Depressive symptomatology was not associated with AD and CVD biomarkers. Both the phosphorylated tau biomarker and depressive symptomatology predicted SCD-memory, and the Aβ42/40 ratio and depressive symptomatology predicted SCD-concentration. Conclusions The role of depressive symptomatology in SCD may differ depending on the stage within the spectrum of preclinical AD (as determined by amyloid-beta and tau positivity), and does not seem to reflect AD pathology. Our findings contribute to the emerging field of subclinical depressive symptomatology in SCD and clarify the association of different types of subjective complaints with distinct syndromic and biomarker profiles.

AbstractBackgroundSubjective cognitive decline (SCD) is topic of mayor interest when identifying individuals at risk for future cognitive impairment and dementia. The degeneration of the cholinergic system is linked to the onset of cognitive symptoms in mild cognitive impairment (MCI) and dementia. Yet, it is uncertain whether the neurodegeneration of the cholinergic system is already present in SCD individuals. This review is the first to synthetize the available data on the association of SCD with multiple markers of degeneration in the cholinergic system.MethodFollowing the PRISMA guidelines, original articles focused on the association of SCD and the cholinergic system were extracted from three databases: Pubmed, WOS and Scopus, in November 2021. Two researchers reviewed the studies independently in a 2‐stepwise approach. The quality of the studies and risk of bias were assessed using FLC 3.0, that allows to systematically evaluate the studies and summarize them easily.ResultAmong 119 studies found in our systematic search, 11 were included in the current review. Seven were cross‐sectional and 4 had a longitudinal design. Most of the studies operationalized SCD based on amnestic cognitive complaints (n = 9, 82%). The cholinergic system measures were based on neuroimaging markers for volume of the basal forebrain and/or functional connectivity, transcranial magnetic stimulation, or biofluid markers (i.e. cerebrospinal fluid (CSF) and plasma). The studies focused on association of SCD with basal brain atrophy, 75% reported reduce volumes in SCD; From those focused on functional connectivity of the cholinergic system, 33% reported poorer connectivity in SCD.ConclusionBased on scientific evidence, neurodegeneration of the cholinergic system is already evident during SCD. Using multiple cholinergic biomarkers, degeneration of cholinergic system in SCD seems to occur with significant structural and functional degeneration of cholinergic nuclei in the basal forebrain and their connections with other brain areas. These findings have implications on identifying individuals with increased vulnerability to cognitive impairment and for targeting individuals that might benefit from cholinergic‐target treatments. Further research is needed to elucidate potential contributors to the cholinergic degeneration in SCD and its impact on cognition and clinical progression.

AbstractBackgroundSubjective cognitive decline (SCD) implies self‐reported cognitive complaints in absence of objective cognitive impairment. SCD has been postulated as an early marker of Alzheimer’s Disease (AD). However, longitudinal studies have linked SCD to future vascular dementia. Thus, we conducted a systematic review and meta‐analysis aiming to synthesise and analyse the available data on the association between SCD and the presence of underlying cerebrovascular pathology measured by MRI.MethodOur study was performed following the PRISMA statement. The search strategy included terms for “subjective cognitive decline” and “white matter signal abnormalities”. It was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin by December 8th, 2021. Two authors screened the studies in a 2‐stepwise approach. Primary studies including cognitively unimpaired adults with subjective cognitive complaints meeting the SCD‐I criteria for SCD that evaluated cerebrovascular pathology based on white matter signal abnormalities (WMSA) on MR images were selected. Study quality was assessed using the FLC 3.0 tool. Meta‐analysis comparing case‐control mean difference of WMSA was performed.ResultOf 240 articles identified, 16 research articles were selected. Of those, 8 case‐control studies were selected for the meta‐analysis. The sample size of the SCD group across the studies ranged from 8 to 906 participants, with age ranged from 40 to 84 years. All eight studies comprised a total of 2.637 SCD individuals. Study quality was deemed moderate (n=6) to high (n=10). The meta‐analysis showed a significant overall effect‐size between the mean WMSA burden of SCD and the controls, that was not significantly heterogeneous (Q(gl=7)=14.20; p=0,04; I2=42,5%). SCD was significantly associated with higher CVP burden based on neuroimaging measures.ConclusionThis is the first study to synthesise and analyse the current evidence on the association between SCD and WMSA. Our findings show the usefulness of SCD as a marker of underlying cerebrovascular pathology. Thus, the potential role of SCD as a preclinical stage of vascular cognitive impairment needs further investigation. Changes in lifestyle (e.g. exercise, diet, smoking cessation), cognitive stimulation or pharmacotherapy may be key to avoid an evolution towards cognitive deterioration in SCD.

AbstractBackgroundSubjective cognitive decline (SCD) in cognitively normal individuals is a relevant predictor of future cognitive decline, dementia, and neurodegeneration. Previous studies showed that the cognitive decline cannot be captured by objective neuropsychological testing in SCD. However, whether sophisticated multivariate approaches such as graph theory can potentially capture subtle cognitive abnormalities in SCD individuals is unknown. This study aimed to assess the cognitive connectome in a relatively large cohort of SCD individuals, in comparison with healthy controls (HC), and assess whether such a connectome differs in SCD across age groups.MethodWe included a total of 390 individuals, of which 211 fulfilled the core SCD criteria proposed by the international SCD Initiative (SCD‐I), and 179 individuals were classified as healthy controls. Participants were stratified into early middle‐age (37–50 years, n = 125), late‐middle‐age (51–64 years, n = 119), and elderly (65–78 years, n = 146) groups. We built cognitive networks from 47 cognitive variables separately for each age and study group using graph theory and compared the groups using global measures of average strength, average global efficiency, average local efficiency, and transitivity.ResultSCD individuals had more segregated networks in all age groups, but more prominently in the late‐middle‐age group. We observed lower within‐module connectivity in SCD individuals, in verbal memory and executive—premotor functions compared with HC. The late middle‐age SCD group showed a pattern of connectivity similar to the elderly HC group. The late‐middle‐age SCD group also showed reduced transitivity compared with the HC. We did not observe significant differences in the rest of the graph measures and in the other groups.ConclusionUsing a sophisticated multivariate approach, we demonstrate that a segregated pattern of cognitive connectivity seems to underlie SCD, particularly in individuals in the age range 51 to 64 years. After the age of 65 years, this pattern tends to be less segregated, contrary to an efficient dedifferentiation process in aging. This, together with subtle signs of brain pathology and other risk factors identified in SCD may increase the likelihood of future cognitive impairment and dementia.