Basic Science and Pathogenesis.

Background: Vascular cognitive impairment/dementia (VD) is the second most prevalent cause of dementia following Alzheimer's disease (AD). VD is characterized by the progression of white matter hyperintensity burden (WMH) and associated neurodegeneration. GFAP, a biomarker for reactive astrogliosis, is associated with Aβ pathology and mediates tau-pathology in preclinical AD.

Basic Science and Pathogenesis.

Background: Dysregulation of cholesterol metabolism contributes to the increase of cerebral vascular diseases, favoring the development of dementia. In this sense, high levels of high-density lipoprotein (HDL) are considered protective against the outcomes associated with cardiovascular diseases. However, little is known about the effect of plasma HDL levels to alterations of cerebral volume in non-vascular AD and vascular AD individuals.

Basic Science and Pathogenesis.

Background: Excessive dietary fat is not only a risk factor for metabolic disorders but also for premature cognitive decline and Alzheimer's disease. Recent findings from our study revealed that even a few days of a high-fat diet (HFD) are sufficient to disrupt hippocampal bioenergetics, activate microglia, and induce cognitive decline in mice. We hypothesize that microglia, rather than merely responding to diet-induced damage, play a critical role in disrupting synaptic homeostasis.

Clinical Manifestations.

Background: Alzheimer's disease (AD) is classically viewed as a predominantly amnestic syndrome, with other cognitive and neuropsychiatric symptoms (NPS) being non-integral associations. Emerging Evidence suggests that within typical AD, these symptoms are core features from the onset.

Methods: We employed K-modes clustering on 2483 cognitively impaired (CI) individuals (CDR ≥ 0.

Clinical Manifestations.

Background: The newly proposed criteria by the AA working group incorporates both biological and clinical stages to characterize the progression of AD. In this study, we aim to evaluate the agreement between these two complementary systems.

Methods: Using 188 participants from McGill TRIAD and 139 from the HEAD cohorts, we categorized participants into biological (0-4) and clinical (0-4) stages using amyloid PET, tau PET(MK-6240), and clinical measures as described by the working group.