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Background: Practice effects are a well‐known cognitive phenomenon that is reduced in patients with Alzheimer's disease (AD). We aimed to investigate whether cognitively unimpaired (CU) individuals within the Alzheimer's continuum (i.e., positive amyloid‐β biomarker) display decreased practice effects on serial neuropsychological testing. Methods: We included 310 CU from four Spanish research centers, classified into controls (n = 250) or Aβ+ (n = 60). In the main cohort (Cohort A; n = 209), participants underwent neuropsychological assessment at baseline and annually during a 2‐year follow‐up (FU1 and FU2). A "long‐term cohort" (Cohort B; n = 101) was employed to assess practice effects over longer time periods (i.e., two follow‐up sessions at years 3 and 6 from baseline). Practice effects were defined as simple discrepancy scores (SDS) by subtracting Z‐scores at FU2 from Z‐scores at baseline for each neuropsychological variable, and linear mixed effects models (LME) were run to assess the temporal evolution of practice effects according to the two groups. Results: There were no cross‐sectional differences between the control and Aβ+ groups in none of the neuropsychological scores at baseline (Fig. 1). The Aβ+ group displayed lower practice effects than the controls in terms of SDS in several neuropsychological outcomes (Fig. 2). In Cohort A, LME showed negative slopes by the Aβ+ group in verbal memory measures such as the free learning score (β = ‐0.37, SD = 0.12, p = 0.0034), delayed free recall (β = ‐0.43, SD = 0.15, p = 0.0047) and delayed total recall (β = ‐0.46, SD = 0.17, p = 0.0069) from the Free and Cued Selective Reminding Test; as well as in language tasks (Boston Naming Test; β = ‐0.26, SD = 0.087, p = 0.0025) and executive function measures (Trail Making Test; β = ‐0.33, SD = 0.12, p = 0.0094) (Fig. 3A). In Cohort B, similar findings were observed in visual memory measures, such as the Rey‐Osterrieth Complex Figure immediate (β = ‐0.80, SD = 0.35, p = 0.024) and delayed (β = ‐1.25, SD = 0.34, p = 0.00038) recall (Fig. 3B). Conclusions: Individuals with normal cognition who are in the Alzheimer's continuum show decreased practice effects over serial neuropsychological testing. Our findings suggest the reduction of practice effects, particularly in memory measures, as an indicator of subtle cognitive decline in the earliest phase of the Alzheimer's continuum and could be particularly relevant for the design and interpretation of primary prevention trials on disease‐modifying therapies. [ABSTRACT FROM AUTHOR]

Background: Blood‐based biomarkers have recently emerged as minimally‐invasive, accessible and relatively inexpensive diagnostic and prognostic tools for people with cognitive impairment. Before being routinely implemented in clinical practice, the diagnostic performance of distinct commercially available assays should be studied in real‐world cohorts. We aimed to study and compare the diagnostic accuracy of different plasma biomarkers measured using two different assay platforms in a memory clinic cohort. Method: Participants were selected from a prospective memory clinic cohort; all had Alzheimer's disease (AD) CSF biomarkers performed. Plasma p‐tau181, GFAP and NfL were measured using Simoa (Quanterix), while plasma p‐tau181, Aβ1‐40 and Aβ1‐42 were quantified using Lumipulse G (Fujirebio). Clinical diagnoses were made according to published criteria, blinded to plasma biomarkers. Aβ status (‐/+) was defined by CSF Aβ concentration using local cutoffs. Result: One hundred and ten participants were included (mean age [standard deviation] 66 [7.8] years, 56% women). Diagnostic categories included 10 cognitively unimpaired controls, 24 with suspected non‐neurodegenerative cause of cognitive impairment (SND), 53 AD, 9 Lewy body disease (LBD, 4 Aβ+) and 14 frontotemporal dementia (FTD, 1 Aβ+). Plasma p‐tau181Quanterix and Aβ1‐42/Aβ1‐40 had the highest diagnostic accuracy (Figure 1) to discriminate between SND and AD (AUC [CI] 0.94 [0.89‐0.99] and 0.94 [0.85‐1]), followed by GFAP (0.93 [0.87‐0.99]), p‐tau181Fujirebio (0.90 [0.82‐0.98]) and Aβ1‐42 (0.71 [0.58‐0.85]). Plasma NfL performed the best to differentiate FTD from SND and AD (AUC 0.95 [0.88‐1] and 0.85 [0.71‐0.99], respectively). For Aβ status discrimination (Figure 2), p‐tau181Quanterix had an AUC [CI] of 0.91 [0.85‐0.96], followed by p‐tau181Fujirebio (0.86 [0.79‐0.93]), Aβ1‐42/Aβ1‐40 (0.85 [0.76‐0.93]) and GFAP (0.84 [0.77‐0.92]) with no statistically significant differences in AUCs. Balanced (Youden index) cut‐offs were calculated to study diagnostic performance, resulting in sensitivities of 79‐83%, specificities of 74‐83% and accuracies of 76‐83%. No combination of plasma biomarkers resulted in a significantly increased discriminative accuracy for Aβ status. All plasma biomarkers were moderately correlated with p‐tau181Quanterix (ρ = 0.40‐0.75, Figure 3). Conclusion: In our cohort, p‐tau181Quanterix, p‐tau181Fujirebio, Aβ1‐42/Aβ1‐40 and GFAP had a high diagnostic performance to discriminate CSF‐defined Aβ status. Plasma NfL identified individuals with FTD. Further studies comparing different plasma biomarkers are needed before implementation in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Little is known about the influence of age at onset (AAO) on plasma biomarkers and their use as prognostic biomarkers in Alzheimer's disease (AD). Method: We selected patients with AD diagnosis with available neuropsychological testing (NPS) at time of diagnosis and two years later, and plasma biomarkers at baseline. NPS battery included Free and Cued Selective Reminding Test (FCSRT), Landscape test (visual memory), Boston Naming Test, Semantic Fluency, BDAE auditory comprehension, Constructional and Ideomotor Praxis, Visual Object and Space Perception (VOSP) Incomplete Letters and Number Location subtests, Trail Making Test (TMT) A and B, Phonemic Fluency, and Digit Span Forward and Backward. NPS scores were compared by AAO: early‐onset AD (EOAD; <65 years) vs. late onset AD (LOAD; >65y). We analyzed plasma biomarkers phosphorilated‐tau181 (p‐tau181), total tau (t‐tau), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin C‐terminal hydrolase L1 (UCHL‐1) using the Quanterix Simoa p‐tau181 Advantage V2 and Neurology 4‐Plex A assays. Group comparisons and linear regressions adjusted by years of education (YOE) were performed in Stata/IC 16.1. Result: Forty‐two participants were included, 23 LOAD and 19 EOAD. Plasma p‐tau181 and GFAP levels were higher in LOAD (Table 1). We did not find differences between LOAD and EOAD in NPS tests at baseline or +2 years (Table 2). Plasma ptau‐181 was associated with progression in MMSE globally, VOSP‐Incomplete letters globally and in EOAD. Plasma NfL were associated to Boston Naming test globally and in EOAD, Semantic fluency test globally, VOSP‐incomplete letters in EOAD, and Free and Total Learning of FCSRT in LOAD. Plasma GFAP was associated to MMSE globally and in EOAD, Free learning of FCSRT in LOAD and VOSP‐Incomplete letters and number location globally. Plasma UCHL‐1 was associated to Semantic fluency test in LOAD (Table 3). Praxis and attention and executive function tests loss were not associated to plasma biomarkers. Conclusion: Plasma p‐tau18, NfL, GFAP and UCHL‐1 were associated to pogression in memory, language and visual tests. They were predominantly associated to memory loss in LOAD and language and visual function loss in EOAD. Results need to be interpreted cautiously due to small sample size. [ABSTRACT FROM AUTHOR]

Background: Plasma Neurofilament light chain (pNfL) is a promising biomarker to discriminate Frontotemporal dementia (FTD) from other diagnoses such as Alzheimer's disease (AD) or psychiatric disorders. Currently, the diagnostic criteria for FTD syndromes are structured hierarchically into "Possible", "Probable" and "Definite" levels depending on the degree of confidence set by biomarkers. We aim to study the diagnostic and prognostic values of pNfL in the different confidence levels of FTD diagnosis. Method: Patients fulfilling criteria for FTD were classified as "Possible", "Probable" or "Definite" FTD based on the current diagnostic criteria. pNfL levels were determined with SiMoA, and then compared to Control and AD groups, as well as within the different levels of confidence in the FTD diagnosis. Result: 187 subjects were included: 37 controls, 79 AD and 71 FTD (11 Possible, 49 Probable and 11 Definite). The FTD group showed higher concentrations of pNfL than the Control (p < 0.001, AUC: 0.817) and the AD groups (p < 0.001, AUC: 0.677) (Figure 1A and 1B). Within the FTD group, pNfL levels differed across the different diagnostic confidence levels (Figure 1C). Subjects with Probable and Definite FTD showed higher levels of pNfL than subjects with Possible FTD (p < 0.001 and p < 0.01 respectively). By contrast, the Possible FTD group did not show differences in pNfL concentrations with the control group. In that sense, the diagnostic value of pNfL varied according to the different grades of diagnostic confidence (Figure 1D), with cases with probable or definite FTD exhibiting an excellent AUC to distinguish from controls (AUC 0.860 and 0.908 respectively), but with no discrimination between possible FTD and controls (AUC 0.583). pNfL presented an excellent performance in the differentiation of structural or functional impairment in the neuroimage (AUC 0.94, and AUC 0.86 respectively) (Figure 2). Finally, higher baseline pNfL levels were associated with worse clinical progression in FTD cases (Figure 3). Conclusion: pNfL were higher in FTD patients compared to controls or AD patients. However, we found significant variation across the different confidence levels of FTD diagnosis. Finally, pNfL predicted neuroimage alterations and a worse clinical progression in FTD patients. [ABSTRACT FROM AUTHOR]

Background: In healthy ageing, there is evidence of sex differences in vulnerability of hippocampal subfields to volume loss. However, this has not been investigated in early‐onset Alzheimer's disease (<65 years; EOAD). Method: We included 106 subjects: 62 EOAD (A+T+N+, MMSE>15) and 44 healthy controls (HC; A‐T‐N‐) that underwent lumbar puncture for analysis of AD biomarkers, 3T‐MRI scan and neuropsychological assessment. Hippocampal subfield segmentation was performed using T1‐weighted images and Freesurfer 6.0. Volume was adjusted by intracranial volume. Adjusted linear models were used to analyze differences between EOAD and HC and differences between sexes. We calculated Cohen's d as a measure of the effect size of volume change by sex, restricted to volume differences between EOAD and HC. In EOAD, we used linear models adjusted by age and education to investigate the association of volume loss with 18 cognition z‐scores. Results were adjusted using Bonferroni correction for multiple comparisons. Result: There were no demographic differences across groups. APOEε4 carriers were higher in EOAD‐female/EOAD‐male than HC‐female. EOAD‐female showed higher T‐Tau and P‐Tau levels than EOAD‐male (all p<0.05; Table1). Comparing EOAD vs. HC, differences were found in volume of all subfields and hippocampus (p<0.05, Bonferroni corrected), except for bilateral parasubiculum and right cornu ammonis (CA) 2/3. No differences were found between EOAD‐female and EOAD‐male (p>0.05). When compared to HC of the same sex, EOAD‐female showed differences in the same regions as the whole sample, while EOAD‐male showed differences in bilateral hippocampal tail and left presubiculum and hippocampus (all p<0.05, Bonferroni corrected, Figure 1). We observed larger effect sizes than in women in these regions, except for left hippocampus (Figure 2). In EOAD, higher volume in left CA2/3 predicted higher memory z‐scores, including free and total learning and delayed total recall (p<0.05 Bonferroni corrected; Figure 3). No associations were found in EOAD‐female nor EOAD‐male. Conclusion: In EOAD, the pattern of volume loss in hippocampal subfields was similar between sexes. However, females showed more marked differences from HC, except for bilateral hippocampal tail and left presubiculum. Further studies are necessary to elucidate the existence of sex differences in EOAD and their implication for cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of early‐onset neurodegenerative dementias (<65 years) can represent a challenge due to their lower frequency respect to late‐onset dementias and atypical forms of presentation. Cognitive impairment has emerged as a frequent complaint after COVID‐19 infection. Method: We retrospectively reviewed (2016‐2021) the demographic and clinical data of the new referrals at our early onset dementia clinic (Hospital Clínic Barcelona). We used Fisher's Exact test and ANOVA in Stata/IC 16.1 to analyze differences between patients visited in 2021, 2020 and the period 2016‐2019. Result: We evaluated 296 patients in 2021, 104 in 2020 and 98 patients/year in 2016‐2019. In 2021, patients had an age at onset (AAO) of 50.1 years, lower than 2020 (53.4) and the period 2016‐2019 (53.0) (p<0.05). The percentage of women in 2021 (69.6%) was higher than 2020 (57.7) and 2016‐2019 (56.0) (p<0.05). Diagnostic delay was lower in 2021 (2.1 years) than 2020 (3.3) and 2016‐2019 (3.0) (p<0.05). No differences were found in Minimental (MMSE) scores (Table 1). In the period 2016‐2021, the number of neurodegenerative diseases (ND) remained steady, the number of subjective cognitive decline (SCD) decreased and the number of non neurodegenerative causes (NNC) experienced a large increase (Table 1), representing 77.7% of visits in 2021. We did not find differences in the type of ND diagnosis in each period (Figure 1A). ND subgroups did not show differences in AAO, sex or MMSE. In 2021, NND presented lower AAO, higher percentage of women, lower diagnostic delay (Figure 1B) and higher MMSE scores than previous years. No differences were found in the SCD group. Cognitive impairment after Covid‐19 accounted for 16.7% of NND in 2020 (n = 8, AAO 50.6 (11.8), 62.5% female, MMSE 26.8(2.3)) and 66.6% of NND in 2021 (n = 153, AAO 49,0 (10.0), 80.1% female, MMSE 27.8 (2.6)). Conclusion: In 2021 we visited approximately three times more patients than in 2016‐2020, among which we observed an increase in NND, mainly patients with cognitive impairment after Covid‐19. On contrast, we found a similar number of ND diagnosis and reduction in SCD. [ABSTRACT FROM AUTHOR]

Background: The application of blood‐based biomarkers for the identification of Alzheimer's disease (AD) and the development of novel digital technologies as cognitive screening tests are critical to moving toward a reliable, more accessible early diagnosis. Our aim was to evaluate the diagnostic performance of a machine learning‐based cognitive assessment known as Altoida's digital neuro‐signature (DNS) in patients with non‐degenerative mild cognitive impairment (ndMCI) and MCI due to AD (prodromal AD) and its association with CSF and plasma biomarkers. Method: Altoida's MCI‐DNS is a 10‐minute cognitive test battery evaluating activities of daily living via motoric and augmented reality tasks. The test consists of placing and finding virtual objects in a real environment and its final score is obtained by weighting multi‐modal digital data features, such as hands' micro‐movements, speed, reaction times, or navigation trajectories. We included 81 participants, classified according to their clinical status and CSF AD biomarker profile as: cognitively unimpaired controls, CTR (n = 10; age = 68.5±5.9; MMSE = 29.4±1.1), ndMCI (n = 25; age = 67.6±7.2; MMSE = 26.9±1.9) and prodromal AD (n = 46; age = 70.8±4.9; MMSE = 24.3±3.3). We further investigated a subsample of participants classified according to their plasma pTau181 levels as measured by SiMoA [cutoff = 1.37 pg/mL (Sarto et al., 2022)]: pTau181 negative (n = 27; age = 68.5±5.9; MMSE = 26.9±2.7) or pTau181 positive (n = 30; age = 70.3±5.5; MMSE = 24.1±3.7). Result: Significant differences were found in MCI‐DNS scores between CTR group and ndMCI (F = 23.5; p<0.001) and prodromal AD (F = 114.4; p<0.001) groups. Also, ndMCI showed higher MCI‐DNS scores than the prodromal AD group (F = 4.53; p<0.05, Fig. 1). ROC curves showed an excellent diagnostic accuracy of the MCI‐DNS in the discrimination between CTR vs. ndMCI (AUC = 0.879) and CTR vs. prodromal AD (AUC = 0.975) (Fig. 1). Further analyses showed differences in MCI‐DNS scores between CSF Aβ42 negative and CSF Aβ42 positive (F = 18.9; p<0.001; Fig. 2), as well as between plasma pTau181 negative and plasma pTau181 positive (F = 6.16; p<0.01; Fig. 2). Finally, MCI DNS scores significantly correlated with CSF Aβ42, CSF Aβ42/pTau ratio, CSF neurofilament‐light chain (NfL) and plasma pTau181 concentrations (Fig. 3). Conclusion: Altoida's MCI‐DNS test allows excellent discrimination between CTR and patients with MCI. MCI‐DNS scores significantly correlate with CSF AD core biomarkers, biomarkers of neurodegeneration and blood‐based biomarkers (i.e., plasma pTau181). [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms, including sleep‐wake disturbances, are more common in Early‐onset Alzheimer's disease (EOAD) than in Late‐onset AD (LOAD)(Falgàs, EurJNeurol2022). The pattern of tau‐related degeneration of wake and sleep‐promoting neurons determine sleep‐wake profiles in neurodegenerative disorders (Oh, JAMANeurol2022). We hypothesize that distinct patterns of noradrenergic (locus coeruleus‐LC) and orexigenic (hypothalamus‐HT) degeneration contribute for the differential sleep‐wake patterns between EOAD and LOAD. Method: A group of 21 participants (7 EOAD, 18 LOAD) with a diagnosis of AD confirmed by cerebrospinal fluid biomarkers (CSF) were recruited from Hospital Clínic de Barcelona. Participants underwent sleep questionnaires (Pittsburg Sleep Quality Inventory‐PSQI and Epworth Sleepiness Scale‐ESS), 2‐week actigraphy (MotionWatch8, CamnTech) and 3T‐neuromelanin‐sensitive MRI to measure locus coeruleus (LC) and hypothalamus (HT) volumes. Sleep, napping, and circadian parameters were obtained (MotionWare). Result: The preliminary results showed no differences in sex (71vs.61% women) or disease stage (CDR 0.5: 85% vs.72%). The amnestic phenotype was prevalent (100 vs.78%). EOAD had longer daytime napping (93.2±74 vs. 58.2±28min, p<0.05), later fell asleep times (0:42am vs. 11:30pm, p<0.05) and higher central phase measure (4.4±0.5 vs. 3.5±1 h, p<0.05, midpoint between fell asleep and wake‐up) than LOAD. Daytime napping correlated with ESS (r = 0.53, p<0.01). Other parameters such as actual sleep time, sleep efficiency, sleep latency, or fragmentation index showed no differences. PSQI did not correlate to any measures. LC‐volumes were lower in EOAD than in LOAD (24.4±7mm3 vs. 33.3±6 p<0.01). In contrast, HT‐ trended towards higher volumes in EOAD (416.8±38 vs. 392.9±36, p = 0.09), being inversely correlated to the age at onset (r = ‐0.47, p<0.05). The central phase measure was inversely correlated to LC‐volumes (r = ‐0.47, p<0.05) but not to HT. Further analyses with increased sample size, CSF noradrenaline and orexin will be performed. Conclusion: Greater daytime sleepiness and circadian dysfunction could be main differing traits regarding sleep‐wake patterns between EOAD and LOAD. An opposite pattern of degeneration within wake‐promoting systems consisting of higher degeneration of the LC‐noradrenergic system and relative preservation of the HT‐orexigenic in EOAD in contrast to LOAD might underlie differing sleep‐wake phenotypes. Age‐related hypothalamic volume loss can be adding to AD driven loss resulting in higher volumes in EOAD. [ABSTRACT FROM AUTHOR]

Background: Currently used biomarkers for the differential diagnosis of cognitive impairment are expensive and/or relatively invasive, limiting their availability to the general population. Blood protein biomarkers have showed promising results for screening, differential diagnosis, and prognosis. We aimed to study the diagnostic performance of plasma p‐tau181 in a daily clinical practice, prospective memory clinic cohort. Method: All patients referred for a first clinical evaluation with suspected cognitive impairment between January 1st, 2020 and March 30th, 2021, were invited to participate in the study. Plasma p‐tau181 was measured using SIMOA technology (Quanterix). Clinical diagnoses were made following current diagnostic criteria and blinded to plasma p‐tau181 results. Result: A total of 232 participants were recruited (mean age 69y, mean MMSE 24), including 25 cognitively unimpaired (CU) controls (mean age 67y, MMSE 28). Clinical diagnoses were AD (82 subjects, 43 of them with prodromal AD [CDR = 0.5]), 83 non‐neurodegenerative cognitive impairment (non‐ND, 75 of them CDR = 0.5), 22 frontotemporal dementia (FTD) and 20 Lewy body disease (LBD). Plasma p‐tau181 levels were statistically higher in AD (mean 2.39 pg/mL) compared with CU (mean 1.09 pg/mL), non‐ND (mean 1.43 pg/mL), FTD (mean 1.69 pg/mL) and LBD (mean 1.64 pg/mL) with a relatively good diagnostic performance for the differential diagnosis between AD and CU, non‐ND, LBD and FTD (AUC of 0.89, 0.80, 0.73 and 0.71, respectively). 128 subjects (55% of the cohort) had specific AD biomarkers (CSF or PET) available. In this subgroup, p‐tau181 differentiated AD from CU and non‐ND (AUC 0.91 and 0.92, respectively) and prodromal AD from CDR = 0.5 non‐ND participants (2.32 vs 1.02 pg/mL, p<0.001, AUC 0.90). Plasma p‐tau181 discriminated between a positive and negative amyloid beta status (defined by CSF/PET) with an AUC of 0.87 and AD subjects from those with a clinical diagnosis of LBD and FTD who had a negative amyloid beta status (AUC of 0.94 and 0.86, respectively). Plasma p‐tau181 correlated with CSF p‐tau181 (rs = 0.48, p<0.001). Conclusion: In our cohort of everyday clinical practice, plasma p‐tau181 is an accurate biomarker for predicting the AD pathophysiological process and discriminating AD from other neurodegenerative and non‐neurodegenerative causes of cognitive impairment. [ABSTRACT FROM AUTHOR]

Integrated crop–livestock systems that intercrop forage crops with grain crops are effective for increasing forage production and improving nutrient cycling and soil health. However, the potential for root competition when maize (Zea mays L.) and sorghum [Sorghum bicolor (L.) Moench] are intercropped with forages in sandy soils is unknown. The objectives of this study were (a) to evaluate the root growth and production characteristics of maize and sorghum intercropped with forage grasses and (b) quantify above‐ and belowground biomass in a tropical integrated cropping system. Two 3‐yr experiments were conducted in which maize and sorghum were intercropped with forage grasses: guineagrass (Panicum maximum Jacq.), ruzigrass [Urochloa ruziziensis (Germ. & Evrard) Crins], palisade grass [Urochloa brizantha (Hochst ex A. Rich.) R. Webster], or an Urochloa hybrid. Monocropped maize and sorghum were used as controls. Fine roots (≤3 mm) were sampled in the monocropped and intercropped systems at soil depths of 1.0 m. Intercropping guineagrass and palisade grass with maize and sorghum resulted in 40% greater dry matter production than intercropping with ruzigrass and the Urochloa hybrid. The positive effect of intercropping forage grasses in the low‐fertility sandy soil was greater for sorghum than for maize because of lower root growth competition. On average, intercropping maize and sorghum with forages increased the total above‐ and belowground biomass by 30 and 50%, respectively, compared with monocropping. In summary, intercropping maize and sorghum with forage grasses is a viable option to enhance biomass during the off‐season in tropical integrated crop–livestock systems. Core Ideas: Intercropping sorghum and maize with grasses is viable for enhancing off‐season biomass.Sorghum production characteristics are not influenced by intercropping with grasses.Competition with grass is stronger for the root system of maize than of sorghum. [ABSTRACT FROM AUTHOR]

Background: Lewy Body Dementia (LBD) is the second most common neurodegenerative dementia. To date, no validated biochemical marker is available to support clinical diagnosis. The development of the Real‐Time Quaking‐Induced Conversion (RT‐QuIC) assay for detecting alpha‐synuclein (aSyn) seeds in biological samples can be a sensitive biomarker specific for the diagnosis easily applicable in a clinical setting. We aimed to describe the diagnostic performance of RT‐QuIC aSyn assay in cerebrospinal fluid (CSF) to diagnose LBD in a clinical cohort with cognitive impairment. Method: A cohort of subjects with cognitive impairment (neurodegenerative and non‐neurodegenerative) with available CSF sample at the moment of first evaluation was selected by convenience sample in our database. Subjects had clinical follow‐ups ranging from 6 months to 12 years and current clinical diagnosis according to established consensus criteria. The diagnostic performance of RT‐QuIC aSyn for the diagnosis of LBD were evaluated. Result: The test was evaluated in 155 subjects (age 65 years (SD 11), MMSE 24 (SD 4.5), 56% male) with the following clinical diagnoses: LBD (n = 40), Alzheimer's disease (AD) (n = 73)(all with compatible CSF profile), frontotemporal dementia (FTD) (n = 7), non‐neurodegenerative mild cognitive impairment (MCI) (n = 21), other neurodegenerative diagnoses (n = 12) and healthy controls (n = 2). aSyn was detected in 33/40 (83%) LBD patients, 7/73 (10%) AD, 0/7 FTD patients, 0/21 MCI patients, 0/12 patients with other neurodegenerative diseases and 0/2 healthy controls. Only 3/7 (42%) LBD subjects with a negative RT‐QuIC asyn fulfilled criteria for LBD (established or prodromal) at the moment of first evaluation as compared with 23/33 (69%) of LBD with positive RTQuIC suggesting a more initial disease in the negative group at the moment of CSF sampling. The sensitivity and specificity of the assay were 83% and 94% respectively for the diagnosis of LBD, with a PPV of 83% and a NPV of 94%. Conclusion: Detection of αSyn seeds by RT‐QuIC has a good performance in identifying patients with LBD in a clinical cohort of cognitively impaired subjects. The test also identifies aSyn co‐pathology in a subgroup of subjects diagnosed with AD. [ABSTRACT FROM AUTHOR]

Background: Early‐onset Alzheimer's Disease presentations (EOAD, under 65) frequently present with atypical phenotypes and a more aggressive disease course with a higher burden of neuropsychiatric symptoms than late‐onset AD (LOAD). Current treatments for sleep and behavioral disturbances are still non‐specific, causing side effects (e.g., sedation, falls). Identifying the underlying changes driving behavioral differences between EOAD and LOAD is crucial to developing tailored treatment avenues. The noradrenergic locus coeruleus (LC), one of the first sites of tau deposition in AD, has been implicated in sleep‐wake patterns and mood regulation. We aim to test the hypothesis that the LC is more affected in EOAD than LOAD by comparing LC volume (neuromelanin‐sensitive MRI) and sleep‐behavioral symptoms in biomarker‐confirmed EOAD and LOAD cohorts. Method: Fifty‐four subjects with AD biomarker‐based diagnosis (20 EOAD, 34 LOAD) were recruited at the Hospital Clínic de Barcelona. All participants and informants completed the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Neuropsychiatric Inventory (NPI) questionnaires to assess the severity of sleep‐wake alterations and neuropsychiatric symptoms. In addition, they underwent a 3T turbospin‐echo MRI to measure LC volume. We compared mean values of LC volume, ESS, PSQI, and NPI between EOAD and LOAD. Furthermore, linear regression models controlling by cognitive status (MMSE) were performed. Result: EOAD and LOAD had similar cognition (MMSE 21.3±5 vs. 22.6±4, respectively), functional status (CDR 0.92±0.1 vs. 0.68±0.1), and prevalence of amnestic phenotype (57 vs. 70%). EOAD compared to LOAD, trended towards higher scores for ESS (7.4±1 vs. 5.1±1, respectively), PSQI (7.3±2 vs. 5.6±1), NPI (21.6±8 vs. 14.6±8), and caregiver distress (9.4±3 vs. 4.7±3). LC volume was lower in EOAD according to preliminary MRI data [n=18, 9 EOAD (21.8±3 mm3), 9 LOAD (29.5±3 mm3)]. Linear regression models showed that MMSE did not influence the EOAD/LOAD effect on LC volume (coef. 7.7, p=0.032). Conclusion: The current preliminary study suggests that LC degeneration is greater in EOAD than LOAD. This difference may explain the EOAD‐associated worse sleep‐wake dysfunction and neuropsychiatric symptoms. Deep phenotyping/comparison of EOAD and LOAD can inform tailored treatment strategies for these behavioral symptoms. [ABSTRACT FROM AUTHOR]

Agricultural management systems are needed to simultaneously enhance production, and improve soil quality. We investigated the effects of intercropped grass on production of corn (Zea mays L.) harvested for silage at 0.20 and 0.45 m height in the summer, as well as on production of subsequent forage, silage soybean [Glycine max (L.) Merr.], and soil responses on a Typic Haplorthox in Botucatu, SP, Brazil. Palisade grass [Urochloa brizantha (Hochst. ex A. Rich.) R. Webster 'Marandu'] was the introduced companion crop with corn (Years 1 and 2), while signal grass [Urochloa decumbens (Stapf) R. Webster 'Basilisk'] was the residual weedy species in comparison. Guinea grass [Urochloa maxima (Jacq.) R. Webster 'Aruãna'] was the introduced companion crop with soybean (Year 3), with only a residual effect of crop systems from the previous 2 yr. When cut at 0.45 m compared with 0.20 m height, corn intercropped with palisade grass had greater leaf nutrient concentrations, agronomic characteristics, forage mass of pasture for grazing by lambs (Ovis aries), greater surface mulch produced, and greater quantity of N, P, and K returned to soil. Greater soil organic matter, P, K, and Mg concentration, and base saturation in the surface soil depth and lower soil penetration resistance at all depths occurred at 0.45 m than at 0.20 m corn silage cutting height intercropped with palisade grass. Analyzing the system as a whole, harvesting corn silage crop with palisade grass intercrop at 0.45 m height was the most viable option in this integrated crop-livestock system (ICLS). [ABSTRACT FROM AUTHOR]

Introduction Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. Methods We conducted a prospective study on 7444 community-dwelling women (aged 65–80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995–2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. Results We found a statistically significant ( P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. Discussion In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors. [ABSTRACT FROM AUTHOR]

There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first International Consensus Conference on this topic. The consensus was a continuous international internet-based process with a final meeting on 28 June 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons, and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting, and ranking. Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic β-blockade, early aspirin therapy, the use of pre-operative intra-aortic balloon counterpulsation, and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. This International Consensus Conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic β-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality. [ABSTRACT FROM AUTHOR]

Background: Early onset Alzheimer disease (EOAD) (age at onset < 65 years) represents an important cause of early‐onset dementia. EOAD has some clinical, pathologic and neuroimaging differences compared to the late onset form of the disease that makes this subset of patients more difficult to diagnose and manage. Our objectives are to describe the clinical‐pathological correlation of a cohort of pathology‐confirmed EOAD, and to compare the findings with our antecedent EOAD cohort. Method: Clinical and neuropathological data of subjects from the Neurological Tissue Bank‐Hospital Clínic/IDIBAPS (Barcelona, Spain, 2010‐2017) with postmortem confirmation of AD and age of onset before 60 years were collected retrospectively and analyzed. Patients with PSEN1, PSEN2 and APP mutations or insufficient clinical data were excluded. The findings were compared with those of our previously reported EOAD cohort (n = 40, 1994‐2009). Result: A total of 36 new patients (44% women) were included. The mean age at onset was 55 years (SD ± 3.5), the mean of diagnostic delay was 2.8 years (SD ± 1.8) and the mean duration of disease was 10.4 years (SD ± 4.2). An onset with typical/episodic memory impairment was observed in 83% of the subjects. There was a lack of clinico‐pathological correlation on initial and final clinical diagnosis in 11% and 8%, respectively. Initial misdiagnoses were frontotemporal dementia (n = 1) and non‐neurodegenerative causes (n = 3), while final misdiagnoses were dementia with Lewy bodies (n = 1), frontotemporal dementia (n = 1) and progressive supranuclear palsy (n = 1). Three patients underwent AD biomarker analysis (3 CSF, 1 amyloid PET), and were consistent with AD profile. The former cohort had less typical/amnestic presentations (χ2 = 4.1, p = 0.04), a trend towards higher percentage of misdiagnoses (23% on initial diagnosis and 20% on final diagnosis, p non‐significant) and a similar diagnostic delay (3.1 years). Neuropathology showed, in addition to AD‐pathology, cerebral amyloid angiopathy in 94% and Lewy‐body copathology in half of patients; these data was similar to the previous cohort. Conclusion: There is a trend towards diagnostic improvement in EOAD, that might be explained by improved diagnostic criteria, increasing experience on EOAD, a higher number of typical presentations and the beginning of use of biomarkers, although diagnostic delay and neuropathological findings remain similar. [ABSTRACT FROM AUTHOR]

An abstract of the article "Atrial fibrillation is independently associated with more severe heart failure. Data from the GISSI Heart Failure Study," by A.P. Maggioni and colleagues is presented.

Background Papillary muscles (PMs) abnormalities may be associated with ECG repolarization abnormalities. We aimed to evaluate the relation between lateral T-wave inversion (TWI) and PMs characteristics in a cohort of athletes with no clinically demonstrable cardiac disease. Methods and Results We included 53 athletes (median age, 20 years; 87% men) with lateral TWI and no evidence of heart disease on clinical and cardiac magnetic resonance evaluation. A group of healthy athletes with normal ECG served as controls. We evaluated the PMs dimensions, such as diameters, area, volume, mass, and ratio between PMs and left ventricular mass, and the prevalence of PMs apical displacement. Compared with controls, athletes with TWI showed PMs hypertrophy with significantly increased PMs diameters, area, volume, and mass. The ratio between PMs and left ventricular mass was 4.4% in athletes with TWI and 3.0% in controls ( P <0.001). A PMs/left ventricular mass ratio >3.5% showed 85% sensitivity and 76% specificity for differentiating between athletes with TWI and controls. Apical displacement of PMs was found in 25 (47%) athletes with TWI versus 9 (17%) controls ( P =0.001). At multivariable analysis, PMs/left ventricular mass ratio and apical displacement remained independent predictors of TWI. Clinical outcome of the athletes with TWI and PMs abnormalities was uneventful despite continuation of their sports activity. Conclusions PMs hypertrophy and apical displacement may underlie otherwise unexplained lateral TWI in the athlete. Lateral TWI associated with PMs abnormalities appears as a distinct anatomo-clinical condition characterized by a favorable outcome.

Background In athletes with ventricular arrhythmias (VA) and otherwise unremarkable clinical findings, cardiac magnetic resonance (CMR) may reveal concealed pathological substrates. The aim of this multicenter study was to evaluate which VA characteristics predicted CMR abnormalities. Methods and Results We enrolled 251 consecutive competitive athletes (74% males, median age 25 [17-39] years) who underwent CMR for evaluation of VA. We included athletes with >100 premature ventricular beats/24 h or ≥1 repetitive VA (couplets, triplets, or nonsustained ventricular tachycardia) on 12-lead 24-hour ambulatory ECG monitoring and negative family history, ECG, and echocardiogram. Features of VA that were evaluated included number, morphology, repetitivity, and response to exercise testing. Left-ventricular late gadolinium-enhancement was documented by CMR in 28 (11%) athletes, mostly (n=25) with a subepicardial/midmyocardial stria pattern. On 24-hour ECG monitoring, premature ventricular beats with multiple morphologies or with right-bundle-branch-block and intermediate/superior axis configuration were documented in 25 (89%) athletes with versus 58 (26%) without late gadolinium-enhancement ( P <0.001). More than 3300 premature ventricular beats were recorded in 4 (14%) athletes with versus 117 (53%) without positive CMR ( P <0.001). At exercise testing, nonsustained ventricular tachycardia occurred at peak of exercise in 8 (29%) athletes with late gadolinium-enhancement (polymorphic in 6/8, 75%) versus 17 athletes (8%) without late gadolinium-enhancement ( P =0.002), ( P <0.0001). At multivariable analysis, all 3 parameters independently correlated with CMR abnormalities. Conclusions In athletes with apparently idiopathic VA, simple characteristics such as number and morphology of premature ventricular beats on 12-lead 24-hour ambulatory ECG monitoring and response to exercise testing predicted the presence of concealed myocardial abnormalities on CMR. These findings may help cost-effective CMR prescription.