Ten histologic sections were sampled from similar cortical regions in each of 84 autopsy brains removed from patients aged 60 to 97 years. The sections were stained by the Congo-red method and examined under polarized light for the presence of cortical (parenchymal) cerebral amyloid angiopathy (CAA). Some degree of CAA was found in 36% of all brains examined, with a higher proportion of patients affected in each successive decade of life. Angiopathy was seen most frequently and was of greater severity in the parietal and occipital gray matter. Overall, it was often a patchy and asymmetric lesion. There was sparing of subcortical white matter and the hippocampi. CAA was most severe in cases of Alzheimer's disease, but occurred in the absence of this condition.

Cerebral microbleeds (CMB) may be indicative of a hemorrhage-prone microangiopathy.To determine if increased numbers of these lesions are predictive of intracerebral hemorrhage (ICH), especially in terms of a distributional association.The authors examined consecutively 227 patients with acute stroke. CMB were counted using T2*-weighted gradient echo MRI data, and old lacunes and leukoaraiosis were also evaluated. The associations between the vascular risk factors and ICH were analyzed. With use of multivariate logistic regression analysis, the locations of the CMB or the old lacunes, which were categorized as being in the corticosubcortical area, the deep gray matter area, or the infratentorial area, were examined with regard to their relationships to the locations of the ICH.The degrees of the CMB (r = 0.43, p < 0.01) and leukoaraiosis (r = 0.20, p < 0.01) were well correlated with the presence of ICH. Multivariate analysis revealed that the grades of the CMB were associated with the presence of ICH (p < 0.01, odds ratio [OR] = 2.67). CMB in the corticosubcortical area (p < 0.01, OR = 5.50) or deep gray matter (p < 0.01, OR = 2.55) were strongly associated with the presence of ICH in the same area, but no such association was observed in the case of CMB in the infratentorial area or in the case of old lacunes in any area.Cerebral microbleeds are strongly associated with the presence of intracerebral hemorrhage, and the distributional associations are also quite strong.

Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular deposition of the amyloid beta-peptide, leading to intracerebral hemorrhage in severe cases. Other than rare familial cases, the only identified risks for CAA are advancing age and accompanying Alzheimer's disease. We tested whether the apolipoprotein E epsilon 4 (apoE epsilon 4) allele was associated with CAA and hemorrhage and whether this association was independent of Alzheimer's disease. The apoE epsilon 4 genotype was determined without knowledge of the pathology for 93 postmortem cases systematically graded for severity of CAA and for 15 patients with CAA-associated intracerebral hemorrhage. We found a significant and independent effect of the apoE genotype in both cohorts. Among the postmortem cases, the presence of apoE epsilon 4 increased the odds ratio for moderate or severe CAA by 2.9-fold, relative to cases without epsilon 4; two copies of epsilon 4 increased the odds ratio 13.1-fold. In the cohort of CAA-associated cerebral hemorrhages, the apoE epsilon 4 allele frequency was 0.40, significantly greater than the control frequency of 0.14. The increase in CAA remained even after controlling for the presence of Alzheimer's disease, suggesting that apoE epsilon 4 is a risk factor for CAA and CAA-related hemorrhage, independent of its association with Alzheimer's disease.

According to the 2018 NIA-AA research framework, Alzheimer's disease (AD) is not defined by the clinical consequences of the disease, but by its underlying pathology, measured by biomarkers. Evidence of both amyloid-β (Aβ) and phosphorylated tau protein (p-tau) deposition-assessed interchangeably with amyloid-positron emission tomography (PET) and/or cerebrospinal fluid (CSF) analysis-is needed to diagnose AD in a living person. Our aim was to test the new NIA-AA research framework in a large cohort of cognitively impaired patients to evaluate correspondence between the clinical syndromes and the underlying pathologic process testified by biomarkers.We retrospectively analysed 628 subjects referred to our centre in suspicion of dementia, who underwent CSF analysis, together with neuropsychological assessment and neuroimaging, and were diagnosed with different neurodegenerative dementias according to current criteria, or as cognitively unimpaired. Subjects were classified considering CSF biomarkers, and the prevalence of normal, AD-continuum and non-AD profiles in each clinical syndrome was calculated. The positivity threshold of each CSF biomarker was first assessed by receiver operating characteristic analysis, using Aβ-positive/negative status as determined by amyloid-PET visual reads. The agreement between CSF and amyloid-PET data was also evaluated.Among patients with a clinical diagnosis of AD, 94.1% were in the AD-continuum, whereas 5.5% were classified as non-AD and 0.4% were normal. The AD-continuum profile was found also in 26.2% of frontotemporal dementia, 48.6% of Lewy body dementia, 25% of atypical parkinsonism and 44.7% of vascular dementia. Biomarkers' profile did not differ in amnestic and not amnestic mild cognitive impairment. CSF Aβ levels and amyloid-PET tracer binding negatively correlated, and the concordance between the two Aβ biomarkers was 89%.The examination of the 2018 NIA-AA research framework in our clinical setting revealed a good, but incomplete, correspondence between the clinical syndromes and the underlying pathologic process measured by CSF biomarkers. The AD-continuum profile resulted to be a sensitive, but non-specific biomarker with regard to the clinical AD diagnosis. CSF and PET Aβ biomarkers were found to be not perfectly interchangeable to quantify the Aβ burden, possibly because they measure different aspects of AD pathology.