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Abstract Background Optical coherence tomography (OCT) enables high-resolution imaging of ocular structures in health and disease. Choroid thickness (CT) is a key vascular retinal parameter that can be assessed by OCT and might be relevant in the evaluation of the vascular component of cognitive decline. We aimed to investigate CT changes in a large cohort of individuals cognitive unimpaired (CU), with mild cognitive impairment due to Alzheimer's (MCI-AD), mild cognitive impairment due to cerebrovascular disease (MCI-Va), Alzheimer’s disease dementia (ADD), and vascular dementia (VaD). Methods Clinical, demographical, ophthalmological and OCT data from the Neuro-ophthalmological Research at Fundació ACE (NORFACE) project were analyzed. CT was assessed in the macula across nine Early Treatment Diabetic Retinopathy Study (ETDRS) quadrants, average thickness, total volume, and subfoveal choroidal thickness. Differences of CT among the five diagnostic groups were assessed in a multivariate regression model, adjusting for demographic and cardiovascular risk factors and OCT image quality. A comparison between manual and automatic CT measurements in a subset of participants was also performed. Results The study cohort comprised 1,280 participants: 301 CU, 196 MCI-AD, 112 MCI-Va, 578 ADD, and 93 VaD. CT was significantly increased in individuals with cognitive impairment compared to those CU, particularly in the VaD and MCI-Va groups and in the peripheral ETDRS regions. No significant differences were found in inner superior, center and subfoveal choroidal thickness. The interaction of sex and diagnosis had no effect in differentiating CT. Mini-Mental State Examination (MMSE) scores were not correlated to CT. Manual and automated CT measurements showed good reliability. Discussion Our findings indicated that peripheral choroidal thickening, especially in patients with cerebrovascular disease, may serve as a potential choroidal biomarker for cognitive decline and suggest different pathogenic pathways in AD and VaD. Further research is required to explore CT as a reliable ocular biomarker for cognitive impairment.

Abstract Background Several studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer’s disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness assessed by OCT and exploring the relationships between the spectrum of cognitive decline (including AD and non-AD cases) and retinal thickness. Methods RNFL and GCIPL thickness at the macula were determined using two different OCT devices (Triton and Maestro). These determinations were tested for association with common single nucleotide polymorphism (SNPs) using adjusted linear regression models and combined using meta-analysis methods. Polygenic risk scores (PRSs) for retinal thickness and AD were generated. Results Several genetic loci affecting retinal thickness were identified across the genome in accordance with previous reports. The genetic overlap between retinal thickness and dementia, however, was weak and limited to the GCIPL layer; only those observable with all-type dementia cases were considered. Conclusions Our study does not support the existence of a genetic link between dementia and retinal thickness.

Abstract Introduction Optical coherence tomography angiography (OCT-A) is a novel tool that allows the detection of retinal vascular changes. We investigated the association of macular vessel density (VD) in the superficial plexus assessed by OCT-A with measures of cerebrovascular pathology and atrophy quantified by brain magnetic resonance imaging (MRI) in non-demented individuals. Methods Clinical, demographical, OCT-A, and brain MRI data from non-demented research participants were included. We analyzed the association of regional macular VD with brain vascular burden using the Fazekas scale assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) assessed in a multiple linear regression analysis. We also explored the associations of macular VD with hippocampal volume, ventricle volume and Alzheimer disease cortical signature (ADCS) thickness assessed in multiple linear regression analyses. All analyses were adjusted for age, sex, syndromic diagnosis and cardiovascular variables. Results The study cohort comprised 188 participants: 89 with subjective cognitive decline and 99 with mild cognitive impairment. No significant association of regional macular VD with the Fazekas categories (all, p > 0.111) and WMH volume (all, p > 0.051) were detected. VD in the nasal quadrant was associated to hippocampal volume (p = 0.007), but no other associations of macular VD with brain atrophy measures were detected (all, p > 0.05). Discussion Retinal vascular measures were not a proxy of cerebrovascular damage in non-demented individuals, while VD in the nasal quadrant was associated with hippocampal atrophy independently of the amyloid status.

Despite the central role attributed to neuroinflammation in the etiology and pathobiology of Alzheimer's disease (AD), the direct link between levels of inflammatory mediators in blood and cerebrospinal fluid (CSF) compartments, as well as their potential implications for AD diagnosis and progression, remains inconclusive. Moreover, there is debate on whether inflammation has a protective or detrimental effect on disease onset and progression. Indeed, distinct immunological mechanisms may govern protective and damaging effects at early and late stages, respectively.This study aims to (i) identify inflammatory mediators demonstrating robust correlations between peripheral and central nervous system (CNS) compartments by means of plasma and CSF analysis, respectively, and (ii) assess their potential significance in the context of AD and disease progression from mild cognitive impairment (MCI) to dementia. To achieve this, we have examined the inflammatory profile of a well-defined subcohort comprising 485 individuals from the Ace Alzheimer Center Barcelona (ACE). Employing a hierarchical clustering approach, we thoroughly evaluated the intercompartmental correlations of 63 distinct inflammation mediators, quantified in paired CSF and plasma samples, using advanced SOMAscan technology. Of the array of mediators investigated, only six mediators (CRP, IL1RAP, ILRL1, IL6RA, PDGFRB, and YKL-40) exhibited robust correlations between the central and peripheral compartments (proximity scores 1.3, p

Abstract Background Advancement in screening tools accessible to the general population for the early detection of Alzheimer’s disease (AD) and prediction of its progression is essential for achieving timely therapeutic interventions and conducting decentralized clinical trials. This study delves into the application of Machine Learning (ML) techniques by leveraging paralinguistic features extracted directly from a brief spontaneous speech (SS) protocol. We aimed to explore the capability of ML techniques to discriminate between different degrees of cognitive impairment based on SS. Furthermore, for the first time, this study investigates the relationship between paralinguistic features from SS and cognitive function within the AD spectrum. Methods Physical-acoustic features were extracted from voice recordings of patients evaluated in a memory unit who underwent a SS protocol. We implemented several ML models evaluated via cross-validation to identify individuals without cognitive impairment (subjective cognitive decline, SCD), with mild cognitive impairment (MCI), and with dementia due to AD (ADD). In addition, we established models capable of predicting cognitive domain performance based on a comprehensive neuropsychological battery from Fundació Ace (NBACE) using SS-derived information. Results The results of this study showed that, based on a paralinguistic analysis of sound, it is possible to identify individuals with ADD (F1 = 0.92) and MCI (F1 = 0.84). Furthermore, our models, based on physical acoustic information, exhibited correlations greater than 0.5 for predicting the cognitive domains of attention, memory, executive functions, language, and visuospatial ability. Conclusions In this study, we show the potential of a brief and cost-effective SS protocol in distinguishing between different degrees of cognitive impairment and forecasting performance in cognitive domains commonly affected within the AD spectrum. Our results demonstrate a high correspondence with protocols traditionally used to assess cognitive function. Overall, it opens up novel prospects for developing screening tools and remote disease monitoring.