Dietary vitamin D intake and changes in body composition over three years in older adults with metabolic syndrome.

Background: Adequate intake of vitamin D through diet may offer benefits in terms of body composition.

Objectives: We aimed to evaluate the longitudinal relationship between dietary vitamin D intake and changes in body composition in older adults over one and three years under the context of a weight loss and lifestyle behavioral intervention.

Design: Longitudinal study.

Plasma Biomarkers for Accelerated Cognitive Decline: A Tool for Targeted Clinical Trial Recruitment.

Background: Detecting Alzheimer's disease (AD) biological hallmarks before clinical symptoms emerge is now possible with available blood‐based biomarkers. However, the rate of cognitive decline varies among individuals at risk of AD, and accurate prognostic blood‐based biomarkers are lacking. Our goal is to identify plasma proteins predictive of fast cognitive decline in asymptomatic individuals at risk of AD.

Plasma biomarkers combinations for prescreening rapid amyloid accumulation in cognitively unimpaired individuals at‐risk of Alzheimer’s disease.

Background: Alzheimer’s disease (AD) blood biomarkers alone can detect amyloid‐β (Aβ) pathology in cognitively unimpaired (CU) individuals. We assessed whether combining different plasma biomarkers improves the detection of Aβ‐positivity and identifies rapid amyloid deposition in CU individuals.

Method: CU participants from the ALFA+ cohort were included.

Neurobiological correlates of grey matter morphometry changes in preclinical Alzheimer’s disease.

Background: The driving mechanisms of structural brain alterations in the earliest stages of Alzheimer's disease (AD) are not well understood. Previous heterogeneous findings in preclinical AD, including subtle atrophy and also increased grey matter (GM) volume, underscore the need for further exploration. This study uses an extensive fluid biomarkers panel to identify pathological drivers behind longitudinal GM changes in cognitively unimpaired (CU) adults.

Use of plasma p‐tau217 as a pre‐screening method for detecting amyloid‐PET positivity in cognitively unimpaired participants: A multicenter study.

Background: Recent results from clinical trials in Alzheimer’s disease (AD) emphasize the importance of treating early‐stage disease. However, recruitment of preclinical AD participants is difficult due to the lack of symptoms, and the costs and/or invasiveness of established CSF and PET tests. We aimed to investigate whether plasma p‐tau217 could be used to pre‐screen cognitively unimpaired (CU) potential participants for amyloid‐β (Aβ) pathology to improve the efficiency of clinical trial recruitment.

Development of a robust blood‐based multi‐pathway biomarker assay for early screening and classification of Alzheimer’s disease.

Background: Alzheimer's disease (AD) is a devastating neurodegenerative disease with delayed diagnosis until the manifestation of symptoms. Although the emergence of blood‐based biomarkers offers hope for easy detection of AD, existing AD‐associated blood biomarkers, known as the “blood ATN biomarkers”, mainly capture the pathological hallmarks of AD, overlooking other AD‐associated biological processes such as inflammation and vascular dysfunctions. Therefore, developing a blood‐based biomarker assay that captures dysregulation beyond the ATN biomarkers may help advance early detection and staging of AD, enabling a comprehensive examination of the disease status

Method: We leveraged ultrasensitive proteomic technology to develop a blood‐based, multiplex biomarker assay for AD.

APOE‐ε4 carriership modifies the association of CCL11 and sVCAM1 plasma protein levels with cognitive performance in individuals at risk of Alzheimer's disease.

Background: In murine models, peripheral blood factors have been identified as having either a brain rejuvenating or ageing effect. However, it is unclear whether these blood factors have similar effects in humans. We aimed at testing the association between these blood factors and cognitive performance in cognitively unimpaired (CU) individuals at risk of Alzheimer’s disease (AD).

Assessing the impact of fasting condition and storage time on plasma Amyloid‐β 42 and 40, pTau181, Nf‐L and GFAP measurements.

Background: Blood biomarkers are essential in identifying Alzheimer's disease (AD) pathology. To ensure their clinical use, it is crucial to understand pre‐analytical factors such as fasting conditions and long‐term storage at ‐80°C. This study evaluates the effect of these factors on plasma biomarker concentrations for detecting AD pathology and neurodegeneration.

PENSA study, results of a 12‐month personalized intensive multimodal lifestyle intervention complemented with epigallocatechin gallate (EGCG) to prevent cognitive decline in ‐ ɛ4 carriers with Subjective Cognitive Decline: a randomized, double‐blinded clinical trial.

Background: Lifestyle interventions targeting multiple Alzheimer’s disease (AD) risk factors are effective strategies to prevent cognitive decline. Emerging evidence suggests synergistic effects between various intervention components, including lifestyle modifications, supplements, and pharmacological approaches. The PENSA study, part of the World‐Wide FINGERs network, is a randomized, double‐blind clinical trial following the Finger 2.

Aberrant resting‐state functional connectivity of the default‐mode network relates to cognitive decline in the earliest Alzheimer's continuum.

Background: Amyloid‐β (Aβ) pathology affects resting state functional connectivity (RSFC), even in cognitively unimpaired (CU) individuals. However, the impact of such an aberrant RSFC on cognitive decline is yet to be determined. Moreover, most prior research focused on fibrillary Aβ deposition to predict RSFC, while early Aβ dysmetabolism as reflected by cerebrospinal fluid (CSF) concentrations has received less attention.

Plasma biomarkers discrimination accuracy of biologically defined Alzheimer’s disease in a memory clinic setting.

Background: Blood‐based biomarkers offer a non‐invasive and cost‐effective means for Alzheimer's disease (AD) detection. In this study, we performed a direct comparison of these novel biomarkers in a memory clinic population to facilitate their implementation into clinical practice.

Method: We included a total of 208 patients with cognitive complaints from the BIODEGMAR cohort at Hospital del Mar (Barcelona, Spain).

Aberrant resting‐state functional connectivity of the default‐mode network relates to cognitive decline in the earliest Alzheimer’s continuum.

Background: Amyloid‐ß (Aß) pathology affects resting state functional connectivity (RSFC), even in cognitively unimpaired (CU) individuals. However, the impact of such an aberrant RSFC on cognitive decline is yet to be determined. Moreover, most prior research focused on fibrillary Aß deposition to predict RSFC, while early Aß dysmetabolism as reflected by cerebrospinal fluid (CSF) concentrations has received less attention.

Neurobiological correlates of grey matter morphometry changes in preclinical Alzheimer's disease.

Background: The driving mechanisms of structural brain alterations in the earliest stages of Alzheimer's disease (AD) are not well understood. Previous heterogeneous findings in preclinical AD, including subtle atrophy and also increased grey matter (GM) volume, underscore the need for further exploration. This study uses an extensive fluid biomarkers panel to identify pathological drivers behind longitudinal GM changes in cognitively unimpaired (CU) adults.

Performance of plasma NTK biomarkers to detect amyloid‐β pathology in cognitively unimpaired individuals at risk of Alzheimer’s disease.

Background: Alzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amyloid and tau) changes, is less understood. We aimed to determine the ability of baseline and longitudinal plasma amyloid‐β (Aβ)42/40, p‐tau181, GFAP and NfL to detect primary pathology in CU individuals at risk of AD.

Unmasking early cerebral blood flow alterations with time‐encoded ASL in Alzheimer's continuum.

Background: Arterial spin labelling (ASL) is a non‐invasive MRI technique for quantifying cerebral blood flow (CBF), used for monitoring changes over the course of a disease or treatment. A crucial parameter in ASL is the post‐labelling delay (PLD), determined by the time it takes for blood to travel from the labeling location to the tissue under investigation. Time‐encoded ASL (te‐ASL) utilizes multiple PLDs for more accurate quantification.

Cognitive reserve is associated with the recruitment of compensatory brain networks in individuals at risk for Alzheimer’s disease.

Background: Cognitive Reserve (CR) refers to the brain's ability to maintain optimal cognitive function despite damage or pathology. The neural implementation of CR is a major research focus, and resting‐state functional connectivity (RSFC) has emerged as a promising imaging correlate of CR. We assessed RSFC as a function of two different proxy measures of CR and further assessed the impact of these brain networks on longitudinal cognitive performance in a sample of cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD).

Genetic predisposition to AD and inflammation determine vulnerable brain regions to air pollution.

Background: The detrimental effects of air pollution on health are well‐documented, yet its impact on brain structure in the early asymptomatic stages of Alzheimer’s disease (AD) remains under‐explored. This study investigated the relationship between air pollution and brain imaging features, focusing on the moderating role of genetic factors associated with AD and inflammation.

Methods: A total of 1,153 individuals from the ALFA cohort, many within the Alzheimer’s continuum, with available genotyping, air pollution estimation and magnetic resonance imaging were included (62.

Early amyloid accumulation and APOE‐ε4 are associated with reduced non‐rapid eye movement slow‐wave activity in cognitively unimpaired adults.

Background: Poor sleep is associated with cognitive decline, and ∼45% of Alzheimer’s disease (AD) patients experience sleep disturbances. Emerging evidence suggests that reduced non‐rapid eye movement (NREM) slow wave sleep (SWS) is linked to amyloid accumulation and APOE ε4‐related genetic vulnerability to AD. Here, we investigate the effects of amyloid and status on SWS, and their interaction, in a cohort of cognitively unimpaired (CU) individuals at higher risk of AD.

Psychological effects of personalized dementia risk disclosure: The Barcelonaβeta Dementia Prevention Research Clinic study.

Background: Approximately 35‐40% of new patients at memory clinics are cognitively intact individuals concerned about their dementia risk. The demand for personalized risk profiling and preventive strategies for those at higher dementia risk is in need of innovative infrastructures. However, disclosing dementia risk estimates raises concerns about potential negative emotional impacts.

Genetic predisposition to clinical AD and AD pathology is differentially associated with baseline and 3‐year period change for specific AD‐related markers.

Background: Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by early changes in brain structure and cognitive function before the age of onset. This study investigated whether the genetic load for clinical AD and AD pathology predicts AD‐related brain and cognitive changes over a 3‐year period, targeting the preclinical phase in cognitively unimpaired (CU) middle‐aged individuals.

Method: The sample of the study was defined by 429 CU middle‐aged participants at risk of AD from the ALFA+ nested cohort with available information on genetics, brain imaging markers and cognitive data [Table 1].

Synaptic dysfunction mediates the association between the CSF t‐tau and PACC change among cognitively unimpaired multiparous women.

Background: CSF t‐tau is considered a marker of neuronal injury in AD and strongly correlates with cognitive impairment. Evidence suggests that women accumulate more tau pathology early in AD than men. However, how pregnancy influences this relationship is unclear.

Longer leukocyte telomere length is associated with lower markers of early Alzheimer's disease pathology, astrocytic reactivity, and synaptic dysfunction.

Background: Leukocyte telomere length (LTL) serves as a proxy for tissue‐specific TL and peripheral immune aging. Its association with aging‐related brain endophenotypes, cognitive functioning, and Alzheimer's disease (AD) risk is established, but the underlying molecular mechanisms remain elusive. Investigating LTL's association with AD biomarkers is crucial for identifying its role in brain resilience and disease progression.

Cognitive reserve is associated with the recruitment of compensatory brain networks in individuals at risk for Alzheimer’s disease.

Background: Cognitive Reserve (CR) refers to the brain’s ability to maintain optimal cognitive function despite damage or pathology. The neural implementation of CR is a major research focus, and resting‐state functional connectivity (RSFC) has emerged as a promising imaging correlate of CR. We assessed RSFC as a function of two different proxy measures of CR and further assessed the impact of these brain networks on longitudinal cognitive performance in a sample of cognitively unimpaired (CU) individuals at risk of Alzheimer’s disease (AD).

Effect of an intensive lifestyle intervention on cystatin C-based kidney function in adults with overweight and obesity: From the PREDIMED-Plus trial.

Background: Large-scale trials evaluating a multicomponent lifestyle intervention aimed at weight loss on kidney function are lacking.

Methods: This was a post hoc analysis of the "PREvención con DIeta MEDiterránea-Plus" (PREDIMED-Plus) randomized controlled trial, including patients with overweight/obesity and metabolic syndrome, measured cystatin C and creatinine. Participants were randomly assigned (1:1) to an intensive weight loss lifestyle intervention (intervention group [IG]) consisting of an energy-restricted Mediterranean diet (MedDiet), physical activity promotion and behavioral support, or a control group (CG) receiving ad libitum MedDiet recommendations.