Alzheimer‐Related Cerebrovascular Disease in Down Syndrome

Abstract

Objective: Adults with Down syndrome (DS) develop Alzheimer disease (AD) pathology by their 5th decade. Compared with the general population, traditional vascular risks in adults with DS are rare, allowing examination of cerebrovascular disease in this population and insight into its role in AD without the confound of vascular risk factors. We examined in vivo magnetic resonance imaging (MRI)-based biomarkers of cerebrovascular pathology in adults with DS, and determined their cross-sectional relationship with age, beta-amyloid pathology, and mild cognitive impairment or clinical AD diagnostic status. Methods: Participants from the Biomarkers of Alzheimer's Disease in Down Syndrome study (n = 138, 50 ± 7 years, 39% women) with MRI data and a subset (n = 90) with amyloid positron emission tomography (PET) were included. We derived MRI-based biomarkers of cerebrovascular pathology, including white matter hyperintensities (WMH), infarcts, cerebral microbleeds, and enlarged perivascular spaces (PVS), as well as PET-based biomarkers of amyloid burden. Participants were characterized as cognitively stable (CS), mild cognitive impairment-DS (MCI-DS), possible AD dementia, or definite AD dementia based on in-depth assessments of cognition, function, and health status. Results: There were detectable WMH, enlarged PVS, infarcts, and microbleeds as early as the 5th decade of life. There was a monotonic increase in WMH volume, enlarged PVS, and presence of infarcts across diagnostic groups (CS < MCI-DS < possible AD dementia < definite AD dementia). Higher amyloid burden was associated with a higher likelihood of an infarct. Interpretation: The findings highlight the prevalence of cerebrovascular disease in adults with DS and add to a growing body of evidence that implicates cerebrovascular disease as a core feature of AD and not simply a comorbidity.

Involvement of cerebrovascular abnormalities in the pathogenesis and progression of Alzheimer’s disease: an adrenergic approach

“…Increasing evidence has indicated the involvement of various alterations in cerebrovascular structure or functions, such as the cerebrovascular microstructure, blood-brain barrier (BBB) integrity, composition of neurovascular unit, cerebrovascular reactivity and cerebral blood flow (CBF), in AD pathophysiology and cognitive defects [ 5 , 6 ]. Recent findings further highlighted the prevalence of cerebrovascular disorders in Down syndrome patients and added to a growing body of evidence implicating cerebrovascular abnormalities as a core feature of AD rather than a simple comorbidity [ 7 ]. Moreover, adrenergic system, including α/β adrenergic receptors and their downstream molecular signaling process, might serve as the key approach to modulate these cerebrovascular abnormalities and progressive neurodegeneration [ 8 ].…”

Complexity Analysis of the Default Mode Network Using Resting-State fMRI in Down Syndrome: Relationships Highlighted by a Neuropsychological Assessment

“…Interest in neuropsychological and cognitive functions in people with DS has promoted the development of assessment tools specifically designed for this population, such as the TESDAD battery [ 10 ] and the Arizona Cognitive Test Battery (ACTB) [ 11 , 12 ]. Moreover, in recent years, there has been a growing interest in introducing neuroimaging techniques to study neuropsychological aspects in people with DS, mainly in studies related to Alzheimer’s disease and dementia [ 13 , 14 ].…”

Effects of chemerin and homocysteine levels and their associations with occurrence and development of ischemic cerebrovascular disease

“…Nowadays this condition is no doubt a tricky issue for public health [ 2 ]. Regarding the pathological basis of the disease, that ischemic necrosis of local brain tissue occurs following atherosclerosis, digital subtraction angiography has been considered as the gold standard for clinical diagnosis of ischemic cerebrovascular disease [ 3 ]. The technology is able to clearly show the degree of intracranial and extracranial artery stenosis and provide reliable reference for disease assessment [ 4 ].…”