Prevalence of small cerebral bleeds in patients with a neurodegenerative dementia: A neuropathological study

doi:10.1016/j.jns.2010.09.031

Journal of the Neurological Sciences

Volume 300, Issues 1–2, 15 January 2011, Pages 63-66

https://doi.org/10.1016/j.jns.2010.09.031 Get rights and content

Abstract

Background

Small cerebral bleeds are frequently observed on magnetic resonance imaging in patients with Alzheimer dementia (AD). Histological confirmations in post-mortem brains are scarce. This study describes the prevalence of cerebrovascular lesions and the quantification of the “bleeding load” in post-mortem brains of patients with neurodegenerative dementias.

Patients and methods

Forty-five brains of AD patients, 8 of dementia with Lewy bodies (DLB) and 12 of fronto-temporal dementia (FTD) were compared to 10 controls. Histological examination was performed for the evaluation of cerebral amyloid angiopathy (CAA), white matter changes (WMCs), micro-infarcts, and cerebral micro- and mini-bleeds (MnBs). The latter were evaluated semi-quantitatively on a coronal section of a whole cerebral hemisphere and on a horizontal section through the pons and cerebellum.

Results

Arterial hypertension (AH) was the main vascular risk factor in the patients with AD and DLB (P < 0.05). MnBs, consisting of small perivascular bleeds, were significantly more frequent (P < 0.001) in AD brains. They were mainly and equally present in the cerebral cortex of AD and DLB brains (P = 0.04). Combined AD and DLB pathologies were present in 15%. CAA and WMCs occurred more frequently in AD brains (P < 0.001). Occasional MnBs were observed in 60% of the controls.

Conclusions

This neuropathological study confirms the frequent presence of MnBs and WMCs in AD brains. The relative high incidence of cortical MnBs in DLB brains is probably due to the high incidence of AH and the frequent association with AD and CAA.

Introduction

Magnetic resonance imaging (MRI) has shown a high incidence of small cerebral bleeds in patients with small-vessel diseases such as cerebral amyloid angiopathy (CAA) and lipohyalinosis [1], [2], [3]. Small cerebral bleeds are also found in asymptomatic patients and in those with arterial hypertension and white matter changes [4], [5], [6]. They are frequently observed in brains of patients suffering from Alzheimer dementia (AD) and are mainly related to CAA [7], [8].

The number of small cerebral bleeds detected depends on the MRI characteristics, such as pulse sequence, sequence parameters, spatial resolution, magnetic field strength and image post-processing [9].

However, there are only a few studies dealing with the direct comparison of the histology of small cerebral bleeds with post-mortem gradient-echo MRI [3], [10], [11], [12], [13] and none were performed in the setting of neurodegenerative dementias.

This neuropathological study aims to describe the prevalence and severity of cerebrovascular lesions, including hemorrhagic ones, in patients with AD, dementia with Lewy bodies (DLB) and fronto-temporal dementia (FTD).

Section snippets

Dementia population

Between 2000 and 2008, 65 consecutive patients with a clinical history of degenerative dementia were autopsied. Ten (15%) patients had been followed-up in a general hospital and detailed clinical data were not available. Fifty-five (85%) patients had been followed-up in the Memory Clinic of the Lille University Hospital.

Controls

During the same period of time, 10 brains from controls were available. The controls consisted of brains of elderly patients without evident signs of cognitive decline, who died

Results

The median age at death was 81 (interquartile range {IQR 74–86}) in the AD, 78 (IQR 76–85) in DLB, 69 (IQR 62–78) in FTD and 69 (IQR 62–78) years in the control group. The AD and the DLB patients were significantly older than the controls (P = 0.002) while those with FTD were of similar age. Female gender represented, respectively, 48.9%, 37.5%, 50.0% and 40.0%.

Three brains with AD had also some cortical Lewy bodies, while in 5 brains with DLB Alzheimer features, stadium I up to III according to

Discussion

The present postmortem study confirms the high incidence of small bleeds in brains of AD patients but also their presence in brains of patients with DLB. Both groups of patients had a frequent history of arterial hypertension.

Several MRI studies have demonstrated the high incidence of small cerebral bleeds in patients with AD [8], [9], [21], [22], [23]. Their presence is also considered as an independent predictor of cognitive impairment in different settings [24], [25], [26].

In the present

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Prevalence of small cerebral bleeds in patients with a neurodegenerative dementia: A neuropathological study

Abstract

Background

Patients and methods

Results

Conclusions

Introduction

Section snippets

Dementia population

Controls

Results

Discussion

Lancet Neurol

Arch Gerontol Geriatr

J Neuroradiol

MRI detection of new hemorrhages: potential marker of progression of amyloid angiopathy

Neurology

Frequency and location of microbleeds in patients with primary intracerebral hemmorhage

Stroke

Histopathologic analysis of foci of signal loss on gradient-echo T2*- weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds

Am J Neuroradiol

MRI evidence of past cerebral microbleeds in healthy elderly population

Neurology

Silent intracerebral microhemorrhages in patients with ischemic stroke. Amsterdam Vascular Medicine Group

Ann Neurol

Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting

Brain

Cerebral amyloid angiopathy in brains of patients with Alzheimer's disease: The CERAD experience, part XV

Neurology

Microbleeds in Alzheimer disease are more related to cerebral amyloid angiopathy than to cerebrovascular disease

Dement Geriatr Cogn Disord

Small chronic hemorrhages and ischemic lesions in association with spontaneous intracerebral hematomas

Stroke

Cerebral microbleeds in CADASIL. A gradient-echo magnetic resonance imaging and autopsy

Stroke

Postmortem MRI as a useful tool for investigation of cerebral microbleeds

Stroke

Direct comparison of histology of microbleeds with postmortem MR images: a case report

Cerebrovasc Dis

Evolution of neuronal changes in the course of Alzheimer's diease

J Neural Transm Suppl

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop

Neurology

Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium

Neurology

Fronto-temporal degenerative dementia. A modern neuropathologic approach

Bull Acad Natl Méd