Biomarkers.

Background: Alpha-synuclein pathology underlies Lewy body diseases and can also occur comorbid to other neurodegenerative pathologies. The lack of an in vivo measure for alpha-synuclein pathology until recently has limited thorough characterization of its brain atrophy pattern, especially during early disease stages. We therefore aimed to assess the association of alpha-synuclein pathology in cerebrospinal fluid (CSF) with magnetic resonance image (MRI) structural measures in three independent cohorts, and separately in clinically unimpaired (CU) and cognitively impaired (CI) individuals, the latter reflecting a memory clinic population.

Biomarkers.

Background: Patterns of regional atrophy and hypometabolism have been observed in dementia with Lewy bodies (DLB). However, determinants of regional vulnerability to structural and functional neurodegeneration remain largely unexplored. First, we investigated the association between regional gene expression and grey matter volumes in probable DLB patients.

Biomarkers.

Background: Alzheimer's disease (AD) is the most common form of dementia, predominantly manifesting as amnestic impairment. However, atypical presentations such as logopenic variant of primary progressive aphasia (lvPPA), posterior cortical atrophy (PCA), corticobasal syndrome (CBS) and frontal AD pose diagnostic challenges. This study presents preliminary data from a retrospective analysis investigating brain functional differences between typical and atypical AD forms.

Biomarkers.

Background: Alzheimer's disease dementia (ADD) is the most common neurodegenerative dementing disorder, explaining about 60-70% of 50 million patients worldwide (www.who.int).

Biomarkers.

Background: The measurement of serum and cerebrospinal fluid (CSF) neurofilaments light chain (NfLs) has been proven promising in differentiating the behavioral variant frontotemporal dementia (bvFTD) from non-neurodegenerative mimics, including primary psychiatric disorders and non-progressive cognitive/behavioral changes. However, studies on this topic are based on clinical diagnosis, which remains challenging and potentially confounded by the overlapping clinical phenotypes. We investigated the role of NfLs in this field by classifying patients based on the presence/absence of pathological longitudinal brain volume changes.

Biomarkers.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly (50-75%) and the causes of the sporadic form are not yet clear. The genetic predisposition is relevant (60-80%), but alone is not sufficient to trigger those initial processes that lead to neurodegeneration and to the slowly atrophy of the brain. Several public datasets containing multimodal data centered on AD have emerged since the beginning of 2004 when ADNI come out.

Biomarkers.

Background: Right temporal variant frontotemporal dementia (rtvFTD), a new recognized entity among the FTD-spectrum, is characterized by right anterior temporal lobe (rATL) atrophy and a peculiar clinical presentation, involving face and emotions recognition, memory, and naming deficits and behavioral disturbances. Clinical diagnosis is challenging, since rtvFTD shares features with both the behavioral variant FTD (bvFTD) and the semantic variant primary progressive aphasia (svPPA), and there is no consensus yet on its designation and characterization. Although rATL neurodegeneration is a hallmark of this syndrome, only a few studies investigated patterns of gray matter (GM) atrophy.

Biomarkers.

Background: Investigating age-related changes in MEG brain networks offers significant potential for comprehending aging trajectories and unveiling anomalous patterns associated with neurodegenerative disorders, such as Alzheimer's disease. In this study, we extended a deep learning model called Fully Hyperbolic Neural Network (FHNN) to embed MEG brain connectivity graphs into a Lorentz Hyperboloid model for hyperbolic space. Through these embeddings, we then explored the impact of aging on brain functional connectivity across multiple decades.

Biomarkers.

Background: The impact of white matter hyperintensities (WMH) on cognitive performance is uncertain due to inconsistent findings. The thalamus is of particular interest given its susceptibility to vascular damage. To test how different vascular risks (Deep/Periventricular WMH and Vascular Scores (VS)) affect thalamic subregional volumes and whether that has any mediating effect on different cognitive domains in healthy controls, mild cognitive impairment (MCI) and AD.

Biomarkers.

Background: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 having the greatest utility. Increased and simplified access to blood biomarkers is crucial for early diagnosis, proper patient management and prompt initiation of disease-modifying treatments. The DROP-AD project investigates the capability of finger-prick collection to accurately measure p-tau217, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).

Biomarkers.

Background: Vigilance and sleep disturbances in Alzheimer's and related diseases, even at the stage of mild cognitive impairment (MCI), have been extensively documented, showing abnormal daytime naps and alterations in the sleep-wake cycle. However, the EEG correlates of the transition from wakefulness to light sleep have not yet been compared between MCI patients due to Alzheimer's vs. other neurodegenerative diseases.

Biomarkers.

Background: With no effective therapy targeting the pathology of genetic frontotemporal lobar degeneration (FTLD), there is a need for easily accessible biomarkers enabling the development of therapeutic agents and for clinical diagnostics. Thus, we aimed to investigate the proteomic changes in plasma of progranulin (GRN) mutation carriers using a novel ultrasensitive antibody-based platform.

Methods: We cross-sectionally evaluated carriers of pathogenic GRN mutations (GRN+) and age- and sex-matched cognitively healthy non-carriers (GRN-) from the University of Brescia.

Biomarkers.

Background: Hippocampal atrophy is an established biomarker of neurodegeneration in Alzheimer's disease, affecting specific subfields (De Flores, La Joie and Chételat, 2015). In this study, we used 7T MRI and advanced diffusion MRI (dMRI) to investigate the relationship between hippocampal subfield volumes and microstructure and assess their sensitivity to cognitive impairment.

Method: Seventeen cognitively impaired (CI; age: 69±8, M/F: 12/5, MMSE: 28) and 22 cognitively unimpaired subjects (CU; age: 62±10, M/F: 6/16) were recruited in the context of the COSCODE project (Ribaldi et al.

Biomarkers.

Background: In clinical settings, the prognosis of patients with subtle cognitive complaints and no imaging evidence of neurodegeneration is often challenging, especially in conditions unrelated to Alzheimer's Disease (AD). We aimed to identify which baseline indicators can help in the clinical decision-making process of patients with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) without AD pathology, by identifying those with faster brain atrophy for their age.

Method: Young-onset SCD and MCI patients (symptoms ≤65yo) were recruited.

Biomarkers.

Background: The Cardiovascular risk factors, aging, and dementia (CAIDE) risk score is a validated tool estimating dementia risk. We investigated the association of CAIDE score with 12 markers of glucose and lipid metabolism, in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) participants.

Methods: The FINGER trial had 1260 participants, aged 60-77 years, with a CAIDE score ≥6, without substantial cognitive impairment.

Effective Management Strategies for Primary Lymphedema of the Lower Extremities: Integrating Conservative and Surgical Therapies in Early and Late Stages.

Introduction: Lymphedema, a debilitating characterized by localized fluid retention and tissue swelling, results from abnormalities in the lymphatic system. In the case of primary lymphedema, this condition is attributed to malformations in lymphatic vessels or nodes, and it is marked by a relentless progression leading to irreversible tissue fibrosis after repetitive inflammation. Many questions regarding its treatment, such as the choice of the type of intervention and the timing, still remain unanswered.

Public Health.

Background: High-income countries (HICs) are over-represented in current global dementia incidence rates, skewing estimates. Variance in diagnostic methods between HICs and low- and middle-income countries (LMICs) is speculated to contribute to the regional differences in rates. Cohort Studies of Memory in an International Consortium (COSMIC) offers a unique opportunity to address these research inequalities by harmonising data from international studies, including representation from LMICs.

Public Health.

Background: Resilience, the ability to maintain normal cognition (cognitive resilience, CR) or brain integrity (brain resilience, BR) despite neuropathological burden, is often quantified using the residual approach. This method calculates residuals from a linear regression where the dependent variable is brain volume or cognition, and the independent variable is neuropathology. Residuals can be corrected to render them independent from the dependent variable, but comparative analyses of residual correction methods within memory clinic populations are scarce.

Public Health.

Background: It is known that cardiometabolic diseases are related to Alzheimer´s Disease.

Method: We included 23 residents of Jalisco with at least one first-degree relative with ADAD (ADADG). We rated the participants using the Clinical Dementia Rating (CDR) as CDR = 0 (n = 20, 87%), CDR = 0.

Public Health.

Background: Sexual minority older adults (SMOAs) report subjective cognitive decline (SCD) more than heterosexual older adults (HOAs). Inconsistent findings have emerged about the risk of cognitive decline in SMOAs. This study aimed to compare the impact of multiple psycho-social risk factors on both objectively assessed and subjectively reported cognitive decline between HOAs and SMOAs.

Public Health.

Background: To estimate the additive associations of cardiometabolic multimorbidity (CMM) and depression on long-term cognitive trajectory in multi-regional cohorts and validate the generalizability of the findings in varying clinical settings.

Method: Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies of Memory in an International Consortium (COSMIC) group, spanning North America, South America, Europe, Africa, Asia, and Australia. Three external validation studies with distinct settings were employed to assess generalizability.

Public Health.

Background: Several clinical guidelines and recommendations have been developed to improve the diagnostic process of patients with dementia, with the aim of optimising patient care and fostering a cost-effective use of resources. However, patient characteristics and organizational factors in clinical practice can lead physicians to deviate from recommendations. In this context, process mining (PM) is a powerful technique for evaluating the compliance of actual to ideal diagnostic pathways, but has never been used in the cognitive field.