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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.

Highlights The pEVs proteome revealed early molecular differences between EOMCI Aβ( +) and Aβ(-) subjects. Olink© neurology proteins from pEVs of EOMCI Aβ( +) patients exhibited a strong negative correlation with CSF p-tau181. The levels of pEVs and CSF Olink© proteins correlated with CSF p-tau181 levels and age. Brain MRI characteristics of EOMCI Aβ( +) patients correlated with pEVs protein levels. pEVs biomarkers only linked early signs of inflammation to brain atrophy in EOMCI Aβ( +) individuals. The correlation of cognitive status and pEVs biomarkers differed between EOMCI Aβ( +) and Aβ(-) patients.

Abstract Background FACEmemory® is the first computerized, self-administered verbal episodic memory test with voice recognition. It can be conducted under minimal supervision and contains an automatic scoring system to avoid administrator errors. Moreover, it is suitable for discriminating between cognitively healthy and amnestic mild cognitive impairment (MCI) individuals, and it is associated with Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers. This study aimed to determine whether FACEmemory scoring is related to performance on classical memory tests and to AD biomarkers of brain magnetic resonance imaging (MRI) and CSF in patients with early-onset MCI (EOMCI). Methods Ninety-four patients with EOMCI from the BIOFACE study completed FACEmemory, classical memory tests (the Spanish version of the Word Free and Cued Selective Reminding Test -FCSRT-, the Word List from the Wechsler Memory Scale, third edition, and the Spanish version of the Rey–Osterrieth Complex Figure Test), and a brain MRI. Eighty-two individuals also underwent a lumbar puncture. Results FACEmemory scoring was moderately correlated with FCSRT scoring. With regard to neuroimaging MRI results, worse execution on FACEmemory was associated with lower cortical volume in the right prefrontal and inferior parietal areas, along with the left temporal and associative occipital areas. Moreover, the total FACEmemory score correlated with CSF AD biomarkers (Aβ1-42/Aβ1-40 ratio, p181-tau, and Aβ1-42/p181-tau ratio). When performance on FACEmemory was compared among the ATN classification groups, significant differences between the AD group and normal and SNAP groups were found. Conclusions FACEmemory is a promising tool for detecting memory deficits sensitive to early-onset AD, but it also allows the detection of memory-impaired cases due to other etiologies. Our findings suggest that FACEmemory scoring can detect the AD endophenotype and that it is also associated with AD-related changes in MRI and CSF in patients with EOMCI. The computerized FACEmemory tool might be an opportunity to facilitate early detection of MCI in younger people than 65, who have a growing interest in new technologies.

Abstract Background Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer’s disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive decline (SCD) has been proposed as a risk factor for progression to AD. There is little data about retinal changes in preclinical AD and their correlation with amyloid-β (Aβ) uptake. Aims We investigated the association of retinal thickness quantified by OCT with Aβ accumulation and conversion to mild cognitive impairment (MCI) over 24 months in individuals with SCD. Methods One hundred twenty-nine individuals with SCD enrolled in Fundació ACE Healthy Brain Initiative underwent comprehensive neuropsychological testing, OCT scan of the retina and florbetaben (FBB) positron emission tomography (PET) at baseline (v0) and after 24 months (v2). We assessed the association of sixteen retinal thickness measurements at baseline with FBB-PET status (+/−) and global standardize uptake value ratio (SUVR) as a continuous measure at v0 and v2 and their predictive value on clinical status change (conversion to mild cognitive impairment (MCI)) at v2. Results Mean age of the sample was 64.72 ± 7.27 years; 62.8% were females. Fifteen participants were classified as FBB-PET+ at baseline and 22 at v2. Every 1 μm of increased thickness in the inner nasal macular region conferred 8% and 6% higher probability of presenting a FBB-PET+ status at v0 (OR = 1.08, 95% CI = 1.02–1.14, p = 0.007) and v2 (OR = 1.06, 95% CI = 1.02–1.11, p = 0.004), respectively. Inner nasal macular thickness also positively correlated with global SUVR (at v0: β = 0.23, p = 0.004; at v2: β = 0.26, p = 0.001). No retinal measurements were associated to conversion to MCI over 24 months. Conclusions Subtle retinal thickness changes in the macular region are already present in SCD and correlate with Aβ uptake.