bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of baseline and longitudinal cognitive reserve on memory ageing in middle and older age adults over a 12‐year period
Authors: Anstey Kaarin J. , Eramudugolla Ranmalee , Zheng Lidan , Brady Brooke , Kootar Scherazad , Wilson Nikki‐Anne , Mortby Moyra E , Chidiac Ben , Cherbuin Nicolas , Leung Yvonne , Andel Ross , Huque Hamidul 
Published: December 2023

AbstractBackground‘Cognitive reserve’ (CR) refers to a model of active protection against cognitive decline conferred by the adaptability of one’s cognitive processes. Research on life‐course accumulation of reserve and impact of factors like gender is limited. We examined long‐term effects of CR on episodic memory in two population‐based cohorts.MethodsParticipants consists of two cohorts from the PATH Through Life project with 12 years (4 waves) of follow‐up, with had an average of 14.6 and 13.9 years of education. The mid‐life cohort (MA) was aged 40‐44 at baseline (mean age 42.6, 52.7% self‐reported female;47.3% male, 0% other gender, N = 2513) and the older cohort (OA) was aged 60‐64 at baseline (mean age 62.5, 48.1% female, 49.9% male, 0% other gender, N = 2403). A baseline composite CR measure included education, occupational complexity, and cognitive and social engagement measured by the RIASEC scales. Episodic memory (Immediate and delayed recall) was assessed with a 16‐word list. Multilevel models adjusting for baseline age, self‐reported gender, race, APOE and non‐English speaking background; evaluated the effect of both baseline and longitudinal change in CR on the longitudinal change in episodic memory.ResultsOn average, women performed better than men on the episodic memory tasks. Compared with participants in the top tertile of CR, those middle and lowest tertiles had larger decline in episodic memory in both MA and OA. Interactions with APOE were not significant, but among those with medium (model derived beta weights 95% CI: 0.35 (0.01‐0.69)) and high (0.48(0.07‐0.90)) CR, women showed less decline than men. Each component of CR (education, occupational complexity, and RIASEC) was protective against decline in immediate and delayed recall. Increase in RIASEC score over time was protective (MA (0.05, (0.04‐0.07); OA 0.13, (0.11‐0.16)) with a larger effect seen in OA.ConclusionThe current study demonstrated protective effects against cognitive decline for all types of CR measured in both middle and older‐age groups. Increases in CR over time were also protective. The benefits of CR were highest for older women who comprise the age and gender group at most risk of Alzheimer’s disease, indicating the need for CR interventions.
Early life factors and individual differences in the brain through the human lifespan – association of intercept or change?
Authors: Walhovd Kristine B 
Published: December 2023

AbstractBackgroundHuman fetal development has been associated with brain health at later stages. In this presentation, I review results of analyses by the center for Lifespan Changes in Brain and cognition (LCBC), on whether and how consistently factors present in utero, including genetics (APOE4; polygenic risk for Alzheimer´s Disease; AD), prenatal drug exposure and, especially, growth in utero, as indexed by birth weight (BW), relates to lifespan brain characteristics and changes.MethodWe investigated associations between BW and cortical surface area, thickness and volume as derived from MRIs, across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4‐82 years of age, w/ 386 monozygotic (MZ) twins, followed for up to 8.3 years w/12,088 brain MRIs).ResultsAssociations of BW and structural brain characteristics appear to be identifiable through the lifespan, with largely topographically consistent effects across samples of varying age. In developmental (ABCD), older adult and aging (UKB) and lifespan (LCBC) longitudinal samples, positive associations between BW and cortical surface area and volume were remarkably stable within and across samples of different age and origin, with spatial correlations in the range r = .51‐.79. In contrast, there was modest and no consistent effect of BW on brain changes. Effects of BW discordance in the twin subsample indicated the effects were partly environmental. This stable effect of an early life factor (BW), is similar to effects through the lifespan of genetic risk for AD, and persistent effects of prenatal opioid and ‐polydrug exposure in childhood and young adulthood.ConclusionThe influence of these early life factors, as here shown for BW, on brain topography, appear in part stable through the lifespan, being reliably seen in development, adulthood, and aging, as an intercept effect. These findings support early life influence on the brain through the lifespan according to a threshold model of brain reserve, rather than a maintenance model. To test experimentally whether early life factors may still influence slopes of brain and cognitive change, a navigation training neuroimaging study of twins with known extent of discordance in BW has been conducted, preliminary data from which is also presented.
Chicken vs. Egg? A Lifespan Perspective on Education and IQ in Cognitive Reserve Research
Authors: Kremen William S. , Elman Jeremy A. , Boyle Rory , Panizzon Matthew S. , Franz Carol E 
Published: December 2023

AbstractBackgroundInferences about cognitive reserve and related constructs may be subject to reverse causation, but too often the possibility of reverse causation is not addressed in research on reserve and resilience. A lifespan perspective can shed light on the relationships among education, IQ, and related constructs and what can be concluded about causality with respect to late‐life cognitive and dementia outcomes.MethodWe use general cognitive ability (GCA) to refer to IQ or IQ‐like measures. We provide examples from the literature plus some new findings examining the effect of cognitive reserve on late‐life outcomes and how modifiable factors may impact reserve and resilience effects. Some of the data presented are from genetically‐informative studies that help to clarify issues related to causality.ResultThere is a bidirectional relationship between education and GCA, but the directional influences change across the lifespan. The relationship is not unidirectional in childhood and adolescence, but during that period more education does increase GCA. The effect reaches an asymptote, and in late adolescence and early adulthood, the causal direction shifts toward GCA driving educational attainment. When both education and GCA are in the same model, both longitudinal phenotypic and Mendelian randomization studies show that GCA is a stronger driver of late‐life cognitive and dementia outcomes than education. Appropriately designed studies often support the idea that occupational complexity and engagement in enriching activities are not directly causal, but are downstream effects of GCA. Finally, earlier lifestyle factors can moderate associations between cognitive reserve and late‐life outcomes. For example, favorable early midlife social/health behaviors can offset advanced brain aging in individuals with lower cognitive reserve (i.e., lower young adult GCA).ConclusionThe results have implications regarding interventions to improve cognitive reserve and resilience, and what the balance should be when it comes to resources for early‐ versus late‐life interventions. The primary direction of causal effects raises questions about how and, importantly, when during the lifespan, increased education, cognitive enrichment/training programs (which may be thought of as a type of education), or other lifestyle factors are likely to increase reserve or resilience, thereby improving cognitive function and reducing dementia risk.
Posterior cortical atrophy in clinical practice
Authors: Maure‐Blesa Lucía , Agüero Pablo , Sainz María José , Téllez Raquel , Lorda‐Sánchez Isabel , Ávila‐Fernández Almudena , Gallego‐Merlo Jesús , Pérez‐Pérez Julián , Gómez‐Tortosa Estrella 
Published: December 2023

AbstractBackgroundA consensus classification framework for posterior cortical atrophy (PCA) was proposed in 2017 to define the core clinico‐pathological syndrome. Main features include a variety of visuospatial deficits associated with posterior cortex dysfunction, together with predominant posterior cortical atrophy. Additional neurological symptoms may be present in what is termed PCA‐plus. Several proteinopathies could be the underlying neuropathology, though in vivo biomarkers only allow for identification of Alzheimer’s disease (AD).MethodWe described the clinical phenotype and biomarkers in a series of patients diagnosed at our memory clinic of PCA (n = 13). Retrospective review of age at onset, family history, cognitive symptoms, neurological deficits, patterns of brain atrophy in MRI, AD biomarkers in CSF, and available genetic analyses.ResultThere were eight women and five men; five had a family history of dementia (Goldman score 3.5) while eight were apparently sporadic cases. Age at onset of symptoms ranged from 30 to 75 years (median 66) and first neurological consultation was 1 to 2 years later, though both psychiatrists and ophthalmologists had already evaluated 46% of the cases. Diagnosis of PCA was established between 5 months and 5 years (mean 2 years) of first assessment. Brain atrophy was parieto‐occipital in 11 cases and temporo‐parietal in two (bilateral in seven, left predominant in four and right in two). Three cases had a PCA‐plus syndrome, one with parkinsonism an another two with CBD features. Five cases (including one with CBD) had AD CSF biomarkers studied, all with an A+T+N+ pattern. APOE was available in eight cases, five carried ε3/ε3 and three ε3/ε4 alleles. The patient with younger onset carried a PSEN1 pathogenic mutation (p.Pro436Gln). Three cases had C9orf72 expansion and plasma progranulin levels analyzed with negative results. Most cases were dependent for activities of daily living after five years of evolution.ConclusionThis series further contributes to the characterization of the clinical heterogeneity of PCA. Anxiety and depression are common in early stages of the disease. Biomarkers are usually consistent with AD.
MONOCYTE‐DERIVED CELLS INVADE AMYLOID PLAQUES IN HUMAN ALZHEIMER’S DISEASE HIPPOCAMPUS
Authors: Mejias‐Ortega Marina , Muñoz‐Castro Clara , Sanchez‐Mejias Elisabeth , Jimenez Sebastian , Trujillo‐Estrada Laura , Vizuete Marisa , Vitorica Javier , Gutierrez Antonia 
Published: December 2023

AbstractBackgroundMicroglia, the brain‐resident myeloid cells, play a major role in the immune responses of the nervous system and in the pathogenesis of Alzheimer’s disease (AD). However, the presence of peripheral myeloid cells in the AD brains, and their contribution to disease progression, remain to be demonstrated.MethodCellular (immunostainings and image analysis) and molecular (qPCR and western blots) approaches have been carried out in post‐mortem hippocampal samples from patients with AD (Braak V‐VI) and age‐matched controls without neurological symptoms (Braak II).ResultsOur study provides evidence that circulating monocytes infiltrate the AD brains. Our findings showed that a high proportion of demented individuals was associated with up‐regulation of genes rarely expressed by microglial cells and abundant in monocytes‐derived cells (MDC), among which stands the scavenger receptor Cd163. These Cd163‐positive MDC invaded the brain parenchyma, acquired a microglial‐like morphology, and were located in close proximity to blood vessels. These cells infiltrated the nearby amyloid plaques contributing to plaque‐associated myeloid cell heterogeneity. Besides, control individuals with high amyloid pathology, showed no signs of MDC brain infiltration or plaque invasion. The MDC infiltration was associated with the progression and severity of AD pathology.ConclusionThese results reveal the co‐existence of distinct myeloid populations associated with amyloid plaques during disease progression, as well their region‐specific contribution to neuroimmune protection. The recruitment of monocytes could be a consequence rather than the cause of the severity of the disease. Whether monocyte infiltration is beneficial or detrimental to AD pathology remains to be fully elucidated. These findings open the opportunity to design targeted therapies, not only to microglia, but also to peripheral immune cell population to modulate amyloid pathology and provide a better understanding of the immunological mechanisms underlying AD progression.Supported by ISCiii grants(PI21‐0915 (to AG),PI21‐00914 (to JV) co‐financed by FEDER funds from European Union, by Junta de Andalucia grants P18‐RT‐2233 (to AG) and US‐1262734 (to JV) co‐financed by Programa Operativo FEDER 2014‐2020, and by grant PPIT.UMA.B1‐2019‐07 (to ESM).
The proteomic profile of Von Economo neurons supports their selective vulnerability in bvFTD
Authors: Gami‐Patel Priya , Li Ka Wan , Hondius David , Paliukhovic Iryna , Rozemuller Annemieke J.M. , Pijnenburg Yolande A.L. , Hoozemans Jeroen , Smit August B. , Dijkstra Anke A. 
Published: December 2023

AbstractBackgroundVon Economo neurons (VENs) are long‐range projection neurons embedded in Layer 5 of the anterior cingulate gyrus (ACC) and frontoinsular cortex. VENs are selectively vulnerable in a number of diseases, most notably in those associated with behavioural, social, and cognitive changes, including the behavioural variant frontotemporal dementia (bvFTD). In particular, VENs of bvFTD donors with TDP43 or FUS pathology appear to be more vulnerable compared to donors with tau pathology. Unravelling the characteristics of VENs and the cause of their vulnerability in specific subtypes of FTD, will provide invaluable insight into disease mechanisms and potential avenues for drug therapeutics.MethodSingle‐cell laser capture microdissection (LCM) in combination with proteomics was used to analyse the proteome of VENs compared to neighbouring Layer 5 pyramidal neurons of the ACC (ACC‐PYR) and the superior frontal gyrus (SFG‐PYR), a region adjacent to the ACC. Immunohistochemistry (IHC) was performed on 10µm thick fresh frozen sections of the ACC and SFG from four neurologically healthy control donors with the neurofilament marker, SMI32. 1000 VENs and three times 1000 ACC‐PYR, and SFG‐PYR were then delineated and captured using LCM. After protein separation, all samples were analysed by label‐free mass spectrometry (LC‐MS/MS) in a data independent manner.ResultAn average 2660 proteins were detected per sample, which accumulated in a total detection of 4718 different proteins over all samples. 69 proteins had a significant change in abundance between VENs and SFG‐PYR, and 36 proteins when VENs were paired against ACC‐PYR. A number of proteins were validated with IHC. GO‐pathway analysis revealed RNA processing and splicing, neurofilament bundle assembly and cytoskeleton organization to be among top deregulated pathways, with many proteins localised to the ribonucleoprotein complex.ConclusionWe show a number proteins involved in RNA processing to be differentially expressed in VENs compared to neighbouring pyramidal neurons. Since TDP43 and FUS proteins are also involved in RNA processing we hypothesise that the selective vulnerability of VENs in specific FTD subtypes is through altered RNA metabolism.
Adherence to healthy lifestyles during a multidomain lifestyle intervention and extended follow‐up among at‐risk population ‐ the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)
Authors: Lehtisalo Jenni , Ngandu Tiia , Laatikainen Tiina , Strandberg Timo , Antikainen Riitta , Tuomilehto Jaakko , Soininen Hilkka , Kivipelto Miia 
Published: December 2023

AbstractBackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a 2‐year multidomain lifestyle intervention to prevent cognitive decline. We have earlier reported that lifestyles improved during the original intervention period, both as participation in the intervention during the 2‐year period and adherence to goals of the intervention. Our aim was to study how these lifestyle changes are maintained during the long‐term period following the active intervention.MethodTotal of 1259 older adults aged 60‐77 participated in the FINGER trial and were randomized into multidomain intervention (n = 631) or control groups (n = 628). A multidomain lifestyle index (MHLI) was calculated based on self‐reported questionnaire using 12 items to obtain a total score representing all four domains of the intervention: diet, physical activity, cognitive activity, and cardiovascular risk factors (range 0 to 24). The questionnaire was repeated annually during the active intervention period and three times thereafter, total of 6 assessments over 11 years. Mixed‐effects regression analyses were executed.ResultAmong the 1259 participants 1117 (88%) completed the original study period and preliminary data were available for 484 at the 11‐year visit (38% of the original cohort; 58% of those invited). Mean MHLI was 13.5 at baseline and lower MHLI score predicted drop‐out during the post‐intervention follow‐up. In the intervention group the MHLI improved during the active period and maintained higher up to 7 years (within‐group change and difference compared with the control group p <0.05 for each year) but no longer at the 11‐year follow‐up. There were no changes in the control group. Age, education, sex, and baseline cognition were all associated with MHLI but did not modify the intervention effect.ConclusionA multidomain lifestyle intervention among at‐risk older adults can have an impact on multidomain healthy lifestyle up to 5 years after the active intervention. Interestingly, average lifestyle did not decrease in the control group either, which would have been expected due to aging. Ongoing detailed analyses will show if this is explained by selective dropout or if participation in the control group may have had some benefits from the participation as well.
Impairment of the locus coeruleus‐transentorhinal cortex pathway in persons at risk of Alzheimer’s disease.
Authors: Quattrini Giulia , Saglia Silvia , Marizzoni Moira , Mega Anna , D'Aprile Ilari , Cattaneo Annamaria , Gasparotti Roberto , Bortoletto Marta , Pievani Michela 
Published: December 2023

AbstractBackgroundRecent studies reported microstructural alterations in the locus coeruleus ‐ transentorhinal cortex (LC‐TEC) pathway in patients with Alzheimer’s disease (AD) but data in subjects at risk of AD (i.e., cognitively intact APOEε4 carriers) are missing. In this study, we apply in‐vivo diffusion weighted images (DWI) to study the effect of APOEε4 on the LC‐TEC pathway in cognitively unimpaired subjects.MethodForty‐five participants (14 APOEε4 carriers: age = 68±7 years, 45% females, MMSE score = 29±0.9; 31 non‐carriers: age = 68±6 years, 57% females, MMSE score = 30±0.6) underwent multimodal 3T MRI and multidomain neuropsychological exams. DWI were corrected for distortions with topup and eddy tools (part of FMRIB’s Software Library – FSL). Microstructural measures as fractional anisotropy (FA), mean (MD), axial (AxD), and radial (RD) diffusivities maps were estimated using the FMRIB’s Diffusion Toolbox (part of FSL) after the exclusion of cerebrospinal fluid voxels. Microstructural integrity of LC‐TEC was assessed using a thresholded probabilistic atlas non‐linearly warped on native maps with FNIRT (part of FSL). A Bonferroni multivariate generalized linear model, corrected for age and sex, was conducted to compare the diffusivity indexes between APOEε4 carriers and non‐carriers. Association with memory functioning (immediate and delayed recall) was also tested using Spearman’s rank correlations test.ResultAPOEε4 carriers and non‐carriers were comparable for cognitive performance (p>.246). Compared to non‐carriers, APOEε4 carriers showed lower FA (p = 0.048) and higher RD (p = 0.036) in the left LC‐TEC. In APOEε4 carriers, left RD negatively correlated with both immediate (rho = ‐0.808, p<0.001) and delayed (rho = ‐0.673, p = 0.025) memory recall.ConclusionMicrostructural alterations of the LC‐TEC pathway are detectable in subjects at‐risk for AD and correlate with lower memory performance. These preliminary results support the view that LC‐TEC impairment may play a role in AD pathophysiology since its early stages.
Cognitive impairment acceleration after late‐life depression in a model of Alzheimer´s disease
Authors: Vegas‐Gomez Laura , Lopez‐Castillo Ines , Fernandez‐Valenzuela Juan Jose , Gutierrez Antonia , Moreno‐Gonzalez Ines 
Published: December 2023

AbstractBackgroundClinical studies suggest that depressive symptoms could be considered an important risk factor for the future development of cognitive impairment and even Alzheimer’s disease (AD). In fact, there is a strong association between depression in later life and AD. The age of onset of AD has been shown to be accelerated in patients with mild cognitive impairment (MCI) with a history of depression, and women appear to be particularly more vulnerable to this condition. In addition, individuals with MCI who present with depressive symptoms have an elevated burden of amyloid‐beta (Aβ), the main toxic protein associated with Alzheimer’s pathology, and a higher risk of developing AD compared to non‐depressed MCI patients. However, it is unknown whether depression can be considered a risk factor for the development of AD. Although it has been described that some transgenic models of AD can develop signs similar to depression in advanced stages, the induction of Alzheimer’s pathology due to a depressive process has not been studied under experimental conditions to emulate late‐life depression as a risk factor for AD.MethodIn this study, we induced chronic unpredictable mild stress (CUMS) in P301S tau transgenic mice to determine whether depression is a cause, rather than a consequence, of the development of AD.ResultThe results of our study indicate that the induction of CUMS in transgenic animals of the disease give rise to changes in depressive state of the animals.ConclusionThe findings generated in this project could provide evidence of depression as a risk factor for AD, its mechanisms of action, use as early biomarkers, as well as the discovery of new therapies for AD.The objectives proposed in this research have specific funding from the Brain and Behavior Research Foundation (27565 2018 NARSAD), the B1‐2019_06 of the Own Plan of the University of Malaga, and the UMA20‐FEDERJA‐ 104FEDER Operational Program Andalusia 2014‐2020, as well as the Ramón y Cajal Program (RYC‐2017‐21879), all awarded to Dr. Inés Moreno.