Cerebral microbleeds in early Alzheimer’s disease

Abstract

We hypothesize that cerebral microbleeds (CMB) in patients with different neuropsychological profiles (amnestic or non-amnestic) and MRI features of vascular damage could provide important information on the underlying pathological process in early Alzheimer's disease. The study was performed at two trial sites. We studied 136 outpatients with cognitive decline. MRI was performed using a magnetic field of 1.5 and 3 T. Neuropsychological assessment included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Addenbrooke's Cognitive Examination (ACE-R), Cambridge Cognitive Examination battery (CAMCOG) (Part 3), Clock Drawing Test, fluency test and the visual memory test (SCT). CSF was examined for standard parameters such as tau, phosphorylated tau, amyloid-β 1-40 and 42 and Qalbumin, in accordance with established protocols and genotype. In 61 patients (45 %), at least 1 CMB was found. Most of the CMBs were described in the amnestic profile (67 %). In 86 % of the cases, multiple CMB were observed. The ratio of Aβ1-40/42 in non-amnestic patients with CMB was significantly lower (mean 0.6) than in patients without CMB (mean 1.2). A notable difference in the albumin ratio as an indicator of the BBB was observed between groups with and without CMB. In the CMP-positive group, the E2 genotype was observed more frequently, and the E4 genotype less frequently, than in the CMB-negative group. Based on the cerebrospinal fluid-serum albumin ratio, we were able to show that patients with CMB present several features of BBB dysfunction. According to logistic regression, the predictive factors for CMB in patients with cognitive decline were age, WMHs score and albumin ratio. We found a significant reduction in the Aβ-amyloid ratio in the non-amnestic profile group with CMB (particularly in the cortical region) in comparison to those without CMB. While this is an interesting finding, its significance needs to be assessed in a prospective follow-up.

Blood-Brain Barrier Dysfunction in Small Vessel Disease Related Intracerebral Hemorrhage

“…AD patients without CMBs ( n = 99) ( 48 ). The eighth study showed increased BBB dysfunction in the form of an increased CSF/serum albumin ratio in patients with cognitive decline with CMBs ( n = 15) compared with patients with cognitive decline but no CMBs ( n = 13) ( 50 ). In contrast, the last study could not identify any difference in BBB dysfunction measured as CSF/serum albumin ratios between AD patients with CMBs ( n = 26) and AD patients without CMBs ( n = 26) ( 52 ).…”

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

“…Damage to blood vessels can lead to pronounced BBB breakdown manifested as cerebral microbleeds (microhaemorrhages), which is frequently seen in AD 86–93 , MCI 94 , and in APOE*ε4 individuals who have increased genetic risk of AD 94 . CAA is one of the main causes of vascular degeneration and lobar microbleeds in AD, and contributes to BBB breakdown, infarcts, white matter changes and cognitive impairment 26 .…”

“…Amyloid deposition in the brain, as detected by 18 F-florbetapir PET, is positively associated with the number of microbleeds in individuals with MCI and AD 99 . Several studies that reported a high prevalence of microbleeds in patients with AD 86–93 or MCI 94 did not perform amyloid-PET imaging 86–93 , however, precluding a direct comparison of microbleeds and CAA severity.…”

Metabolic Risk Factors of Alzheimer’s Disease, Dementia with Lewy Bodies, and Normal Elderly: A Population-Based Study

“…The gradual spreading of the intracellular aggregation of hyperphosphorylated tau (P-tau) in the brain is associated with AD progression [ 1 ]. Studies also reveal the association between cerebral microbleeds and P-tau [ 33 , 34 ]. Interestingly, our data did not reveal increased hemorrhagic stroke in both AD and DLB patients when compared to NC individuals.…”