Abstract
Despite existing criteria, differential diagnosis of Vascular Dementia (VD) and Alzheimer's disease (AD) remains difficult. The aim of this study is to figure out cognitive and biomarker profiles that may help to distinguish between VD, AD and AD + Cerebral Small Vessel Disease (CSVD). We examined a cohort of patients with CSVD (n = 92). After stratification of cognitive impaired patients (n = 59) using the standard CSF beta-amyloid 42/40 ratio cut-off point of 0.975, we obtained two groups which differed with respect to several features: 32 patients with normal beta-amyloid 42/40 ratio (>0.975) showed markedly impaired blood-brain-barrier function as indicated by an elevated albumin ratio (median 8.35). They also differed in cognitive profiles when compared to 27 patients with AD typical beta-amyloid ratio and normal albumin ratio. We also enrolled an additional group of patients with AD (no significant CSVD on MRI, n = 27) which showed no impairment of the blood-brain-barrier. We showed a negative correlation between the albumin ratio and executive cognitive function (p = 0.016) and a negative correlation between memory function and typical AD markers like Tau (p = 0.004) and p181-Tau (p = 0.023) in our cohort. We suppose that the group of patients with normal beta-amyloid ratio represents VD while patients in the other groups represent AD+CSVD and pure AD. Our results support the idea that a dysfunction of the blood-brain-barrier might be contributing factor in the development of cognitive decline in CSVD as it seems to be of more importance than the severity of white matter lesions.
Highlights
There is an ongoing discussion on pathophysiology, diagnostic criteria and phenotypic diversity of vascular dementia (VD)
Mixed forms of Alzheimer’s disease (AD) and VD, especially dementia caused by CVSD, do not appear in most criteria and they are not considered in most studies [6]
Objectives of this study The main objective of this study is to identify parameters such as neuropsychological test profiles and/or CSF biomarkers which will allow the discrimination between patients with sole Cerebral Small Vessel Disease (CSVD) from those with AD+CSVD and pure AD
Summary
There is an ongoing discussion on pathophysiology, diagnostic criteria and phenotypic diversity of vascular dementia (VD). It is supposed to be the second leading cause of dementia after Alzheimer’s disease (AD) but its prevalence remains unclear since studies differ from 0.03-58% in autopsy series[1]. Criteria like NINDS-AIREN[2] refer to different entities of VD including the use of imaging (territorial or lacunar strokes), clinical features and causal relation with cerebral ischemic stroke. Over the last years many studies have reported that vascular risk factors contribute to both, VD and AD. Many cases of dementia are considered mixed VD and AD and vascular risk factors might play a major role [3]. Mixed forms of AD and VD, especially dementia caused by CVSD, do not appear in most criteria and they are not considered in most studies [6]
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