Introduction: Synaptic damage, axonal neurodegeneration, and neuroinflammation are common features in Alzheimer's disease (AD), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD). Methods: Unicentric cohort of 353 participants included healthy control (HC) subjects, AD continuum stages, genetic AD and FTD, and FTD and CJD. We measured cerebrospinal fluid neurofilament light (NF-L), neurogranin (Ng), 14-3-3, and YKL-40 proteins.Results: Biomarkers showed differences in HC subjects versus AD, FTD, and CJD. Disease groups differed between them except AD versus FTD for YKL-40. Only NF-L differed between all stages within the AD continuum. AD and FTD symptomatic mutation carriers presented differences with respect to HC subjects. Applying the AT(N) system, 96% subjects were positive for neurodegeneration if 14-3-3 was used, 94% if NF-L was used, 62% if Ng was used, and 53% if YKL-40 was used.

Our results suggest that SCD-Q items related with language and executive decline may help in prediction algorithms to detect preAD. Validation in an independent population is needed.

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Introduction:The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) ε4 carriership, and neuropsychiatric symptoms with amyloid positivity. Results: Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE ε4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informantconfirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. Discussion: Next to age, setting, and APOE ε4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.

Background and purpose Several diagnostic biomarkers are currently available for clinical use in early‐onset cognitive impairment. The decision on which biomarker is used in each patient depends on several factors such as its predictive value or tolerability. Methods There were a total of 40 subjects with early‐onset cognitive complaints (<65 years of age): 26 with Alzheimer's disease (AD), five with frontotemporal dementia and nine with diagnostic suspicion of non‐neurodegenerative disorder. Clinical and neuropsychological evaluation, lumbar puncture for cerebrospinal fluid (CSF) AD core biochemical marker determination, medial temporal atrophy evaluation on magnetic resonance imaging, amyloid‐positron emission tomography (PET) and 18F‐fluorodeoxyglucose‐PET were performed. Neurologists provided pre‐ and post‐biomarker diagnosis, together with diagnostic confidence and clinical/therapeutic management. Patients scored the tolerability of each procedure. Results Cerebrospinal fluid biomarkers and amyloid‐PET increased diagnostic confidence in AD (77.4%–86.2% after CSF, 92.4% after amyloid‐PET, P < 0.01) and non‐neurodegenerative conditions (53.6%–75% after CSF, 95% after amyloid‐PET, P < 0.05). Biomarker results led to diagnostic (32.5%) and treatment (32.5%) changes. All tests were well tolerated. Conclusions Biomarker procedures are well tolerated and have an important diagnostic/therapeutic impact on early‐onset cognitive impairment.

NIA-AA diagnostic criteria include volumetric or visual rating measures of hippocampal atrophy (HA) as a diagnostic biomarker of Alzheimer's disease (AD). We aimed to determine its utility as a diagnostic biomarker for early onset Alzheimer's disease (EOAD) by assessing Medial Temporal Atrophy (MTA) and hippocampal volume (HV) determination. MTA score and HV quantified by FreeSurfer were assessed in 140 (aged ≤65) subjects with biomarker supported diagnosis: 38 amnesic (A-EOAD), 20 non-amnesic (NA-EOAD), 30 late onset AD (LOAD), 20 fronto-temporal dementia (FTD) and 32 healthy controls (HC). The results showed that the proportion of MTA ≥ 1.5 was higher on LOAD and FTD than EOAD and HC but none of the MTA thresholds (≥1, ≥1.5 and ≥ 2) showed acceptable diagnostic accuracy. LOAD had lower HV than the other groups. A-EOAD HV was lower than NA-EOAD and HC but equal to FTD. The 6258 mm3 cut-off showed good diagnostic accuracy between A-EOAD and HC. Both tools showed a moderate inverse correlation. In conclusion, MTA has a limited diagnostic utility as an EOAD biomarker as it does not discriminate AD from FTD or HC in initial symptomatic stages. HV may discriminate A-EOAD from HC but not from FTD.

Highlights Posterior cortices, hippocampus and amygdala track atrophy in EOAD over two years. The medial temporal cortex is unaltered in EOAD at early stages. EOAD exhibited a posterior-to-anterior gradient of cortical loss after two years. EOAD subcortical volume loss extends beyond hippocampus and amygdala after two years. Cerebrospinal fluid biomarkers might predict atrophy rates in EOAD.

Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early-onset AD (EOAD) and FTLD structural alterations and CSF biomarker levels. We included 138 subjects (64 EOAD, 26 FTLD, and 48 controls), all of them with a 3T MRI brain scan and CSF biomarkers available (the 42 amino acid-long form of the amyloid-beta protein [Aβ42], total-tau protein [Ttau], neurofilament light chain [NfL], neurogranin [Ng], and 14-3-3 levels). We used FreeSurfer and FSL to obtain cortical thickness (CTh) and fraction anisotropy (FA) maps. We studied group differences in CTh and FA and described the "AD signature" and "FTLD signature." We tested multiple regression models to find which CSFbiomarkers better explained each disease neuroimaging signature. CTh and FA maps Neus Falgàs, Mariona Ruiz-Peris, Albert Lladó, and Raquel Sánchez-Valle authors contributed equally to this work.