Journal Article

Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline

Jacobs, Heidi I. L., Aalten, Pauline, Verhey, Frans R., Hampel, Harald, Vos, Stephanie J. B., van der Flier, Wiesje M., Ramakers, Inez H.G.B., Bos, Isabelle, Freund-Levi, Yvonne, Verbeek, Marcel M., Wallin, Åsa K., Oleksik, Ania, Visser, Pieter Jelle, Tsolaki, Magda, van Buchem, Mark A., Soininen, Hilkka, Olde Rikkert, Marcel, Scheltens, Philip

2017

Overview

Background Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia. Methods We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort ( n  = 99) and the LeARN ( n  = 50) and DESCRIPA ( n  = 122) multicenter studies. CSF Aβ 1–42 and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Aβ and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (−) of Aβ and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics. Results MTA and t-tau were elevated in the Aβ − WMH+, Aβ + WMH−, and Aβ + WMH+ groups. MTA was most severe in the Aβ + WMH+ group compared with the groups with a single pathology. Both WMH and Aβ were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline. Conclusions In the present study, we found an additive association of Aβ and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Aged / Alzheimer’s disease / Amyloid / Amyloid beta-Peptides / Amyloid beta-Peptides - metabolism / Apolipoproteins E / Apolipoproteins E - genetics / Atrophy / Biomarkers / Biomarkers - cerebrospinal fluid / Biomedical and Life Sciences / Biomedicine / Brain / Brain - diagnostic imaging / Brain - metabolism / Cerebrospinal fluid / Cerebrovascular disease / Cerebrovascular Disorders / Cerebrovascular Disorders - diagnostic imaging / Cerebrovascular Disorders - genetics / Cerebrovascular Disorders - metabolism / Clinical Medicine / Cognition / Cognitive Dysfunction / Cognitive Dysfunction - diagnostic imaging / Cognitive Dysfunction - genetics / Cognitive Dysfunction - metabolism / Cohort Studies / Dementia / Dementia - diagnostic imaging / Dementia - genetics / Dementia - metabolism / Disease Progression / Female / Geriatric Psychiatry / Geriatrics/Gerontology / Glycoproteins / Humans / Klinisk medicin / Life Sciences / Magnetic Resonance Imaging / Male / Medial temporal lobe atrophy / Medical and Health Sciences / Medicin och hälsovetenskap / Mental Status and Dementia Tests / Middle Aged / MRI / Neurodegeneration / Neurologi / Neurology / Neurosciences / Phosphorylation / Psychological aspects / Tau / tau Proteins / tau Proteins - metabolism