The Impact of Cerebral Amyloid Angiopathy in Various Neurodegenerative Dementia Syndromes: A Neuropathological Study.

PURPOSE: The Boston criteria for cerebral amyloid angiopathy (CAA) have to be confirmed by postmortem examination. The present study investigates the incidence and the cerebrovascular impact of the severity of CAA in various neurodegenerative dementia diseases. MATERIAL AND METHODS: 208 patients underwent an autopsy. They consisted of 92 brains with Alzheimer's disease (AD), 46 with frontotemporal lobar degeneration (FTLD), 24 with progressive supranuclear palsy (PSP), 21 with Lewy body dementia (LBD), 5 with corticobasal degeneration (CBD), and 20 controls. In addition to the macroscopic examination, a whole coronal section of a cerebral hemisphere, at the level of the mamillary body, was taken for semiquantitative microscopic evaluation of the small cerebrovascular lesions. RESULTS: CAA is present in 2/3% of the AD brains of which half of them have a severe form, grade 3. Only the latter displays more cerebrovascular lesions. CAA is present in 45% of the LBD brains. Cortical microinfarcts are only more frequent in the CAA grade 3 group. In LBD additional AD pathology is present in 41% of the CAA grade 0, 83% in grade 1-2, and 100% in grade 3. In PSP only 21% had CAA grade 1-2. In FTLD, CBD, and normal controls no CAA pathology is observed. CONCLUSIONS: The present study shows that CAA is most frequently associated to AD but that only the severe form displays more cerebrovascular lesions. LBD is the second most frequent disease associated to CAA with a clear correlation between the incidence of the associated AD features and the increasing severity of the CAA. In PSP only 21% display mild CAA features. PSP, tau-FTLD, and CBD are part of the Pick complex diseases, who are known to have a favourable vascular profile which can explain their low incidence of cerebrovascular lesions, in contrast to AD and LBD brains.

Aging and cerebrovascular lesions in pure and in mixed neurodegenerative and vascular dementia brains: a neuropathological study.

INTRODUCTION: The prevalence of dementia is increasing in our aging population. Because of the complexity of disease pathology, dementia classifications remain controversial. The present post-mortem study investigates whether there are age differences between dementia brains with a single pure neurodegenerative or cerebrovascular disease and those with mixed pathological features. Also, the impact of these vascular lesions is compared. MATERIAL AND METHODS: A total of 132 dementia brains with a pure neurodegenerative or cerebrovascular disease and 84 with mixed features were examined. Main age and gender distribution were compared between the overall group of pure and of mixed dementia. Also, the most common subgroups were compared separately. In addition to the detection of macroscopic visible lesions, a whole coronal section of a cerebral hemisphere, at the level of the mamillary body, was taken for semi-quantitative microscopic evaluation of white matter changes (WMCs), cortical micro-bleeds (CoMBs), and cortical micro-infarcts (CoMIs). RESULTS: Overall, patients with mixed dementia were at death significantly older than those with pure dementia. According to the main diagnosis, the pure forms of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) were more common in the younger age groups while in the older ones the mixed form of Lewy body disease (LBD) predominated. Neuropathological examination revealed an increased severity of cerebral amyloid angiopathy (CAA), territorial infarcts, lobar haematomas, and CoMIs in the mixed AD group. In FTLD only CoMIs were increased in the mixed group, while in LBD no differences in severity of all cerebrovascular lesions were observed. Lacunar infarcts were more frequent in pure vascular dementia, while CAA predominated in the mixed one. CONCLUSIONS: Mixed dementia during the aging process is mainly due to the severity of AD and LBD pathologies combined with CAA-related cerebrovascular lesions.

Pathogenic variants in the ABCC6 gene are associated with an increased risk for ischemic stroke.

Ischemic stroke causes a high mortality and morbidity worldwide. It results from a complex interplay of incompletely known environmental and genetic risk factors. We investigated the ABCC6 gene as a candidate risk factor for ischemic stroke because of the increased ischemic stroke incidence in the autosomal recessive disorder pseudoxanthoma elasticum, caused by biallelic pathogenic ABCC6 variants, the higher cardiovascular risk in heterozygous carriers and the established role of ABCC6 dysfunction in myocardial ischemia. We established segregation of a known pathogenic ABCC6 variant (p.[Arg1314Gln]) in 11/19 family members of an ischemic stroke patient in a large multigenerational family suffering from ischemic stroke and/or cardiovascular disease at a relatively young age. In an independent case-control study in 424 ischemic stroke patients and 250 healthy controls, pathogenic ABCC6 variants were 4.9 times more frequent (P = 0.036; 95% CI 1.11-21.33) in the ischemic stroke patient cohort. To study cellular consequences of ABCC6 deficiency in the brain, immunostaining of brain sections in Abcc6-deficient mice and wild-type controls were performed. An upregulation of Bmp4 and Eng and a downregulation of Alk2 was identified in Abcc6-/- mice, suggesting an increase in apoptosis and angiogenesis. As both of these processes are induced in ischemia, we propose that a pro-ischemic state may explain the higher risk to suffer from ischemic stroke in patients carrying a pathogenic ABCC6 variant, as this may lower the threshold to develop acute ischemic events in these patients. In conclusion, this study identified heterozygous ABCC6 variants as a risk factor for ischemic stroke. Further, dysregulation of Bmp (Bmp4, Alk2) and Tgfß (Eng) signaling in the brain of Abcc6-/- mice could lead to a pro-ischemic state, lowering the threshold to develop acute ischemic events. These data demonstrate the importance of a molecular analysis of the ABCC6 gene in patients diagnosed with cryptogenic ischemic stroke.

Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.

Motor evoked potentials in patients with chronic whiplash-associated disorder grade II.

BACKGROUND AND PURPOSE: It is common belief that psychological problems influence the persistence of complains in patients with so-called mild whiplash-associated disorders (WADs). The usefulness of motor evoked potentials (MEPs) is investigated in patients with grade II WAD and remaining complains for more than 6 months. PATIENTS AND METHODS: Twenty consecutive patients, aged between 24 and 58 years, with persistent neck pain for months after a car accident were included. All patients had a magnetic resonance imaging (MRI) of the cervical spine and cord. Central (CMCT) and peripheral motor conduction times (PMCT) were evaluated by registration in the biceps brachii muscle (C5-C6) and in the abductor digiti minimi muscle (C7-C8-Th1). RESULTS: Thirteen patients had prolonged CMCT or/and PMCT compared to 7 with normal values. On MRI discus bulging C5-C6, without abnormal signal changes in the cervical spinal cord was observed in 6 of the patients with disturbed MEPs compared to 3 without. Out of 7 patients, who had repeated MEPs after 6 months, 3 of them had an improvement of their conduction time. The patients with prolonged MEP conduction times were older than those with normal values (p=0.007). CONCLUSIONS: MEP examination has to be performed in all patients with persistent complains even in the absence of objective neurological signs and non-significant changes on imaging.

Cerebrovascular Lesions in Mixed Neurodegenerative Dementia: A Neuropathological and Magnetic Resonance Study.

BACKGROUND: In elderly brains of demented patients, Alzheimer and Lewy body pathology (LBP) are frequently associated. Cortical microinfarcts (CoMIs) are more observed in Lewy body disease, even in the absence of cerebral amyloid angiopathy (CAA). The present neuropathological and 7.0-tesla MRI studies investigate whether CoMIs are also more frequent in mixed neurodegenerative dementia syndromes. SUMMARY: Both examinations revealed that CoMIs are increased to different degrees in mixed dementia syndromes according to the severity of the LBP. They were mainly associated with a trend of older age and arterial hypertension in the patients with the most severe LBP. Messages: The increased number of CoMIs in mixed dementia syndromes with LBP is mainly due to the associated cerebrovascular pathology, even in the absence of CAA.

Frequency and topography of small cerebrovascular lesions in vascular and in mixed dementia: a post-mortem 7-tesla magnetic resonance imaging study with neuropathological correlates.

Introduction: Mixed dementia (MixD) refers to a combination of definite Alzheimer's disease (AD) and vascular encephalopathy. The existence of a "pure" type of vascular dementia (VaD) is controversial. There is a need to find magnetic resonance imaging (MRI) characteristics allowing the distinction between VaD and MixD. The present post-mortem 7.0-tesla MRI compares the frequency or severity and the topography of the small cerebrovascular lesions in brains of patients with VaD and with MixD. Material and methods: Based on neuropathological criteria, 14 brains were classified as VaD, 24 as MixD and 11 as controls. Three coronal sections of a cerebral hemisphere and a horizontal section of a cerebellar hemisphere underwent T2 and T2* 7.0-tesla MRI examination. The mean values and topographic distribution of white matter changes (WMCs), lacunar infarcts (LIs), cortical microbleeds (CoMBs) and cortical microinfarcts (CoMIs) were determined and compared between the different groups. Results: Compared to the controls, both VaD and MixD brains had significantly more severe WMCs and increased numbers of CoMBs and CoMIs. Lacunar infarcts predominated only in the VaD cases. On mutual comparison of VaD and MixD brains, CoMBs and CoMIs predominated in the frontal lobe and the cerebellum of VaD, while were mainly present in the occipital lobe of MixD. White matter changes predominated in the temporal lobe of MixD cases. Lacunar infarcts were significantly increased in the corona radiata and putamen of VaD patients. Conclusions: The present post-mortem MRI study shows clear differences in the distribution and the types of cerebrovascular lesions on high-field MRI, confirming that VaD and MixD are different diseases. .

Neuroimaging in vascular cognitive impairment: a state-of-the-art review.

Imaging is critical in the diagnosis and treatment of dementia, particularly in vascular cognitive impairment, due to the visualization of ischemic and hemorrhagic injury of gray and white matter. Magnetic resonance imaging (MRI) and positron emission tomography (PET) provide structural and functional information. Clinical MRI is both generally available and versatile - T2-weighted images show infarcts, FLAIR shows white matter changes and lacunar infarcts, and susceptibility-weighted images reveal microbleeds. Diffusion MRI adds another dimension by showing graded damage to white matter, making it more sensitive to white matter injury than FLAIR. Regions of neuroinflammatory disruption of the blood-brain barrier with increased permeability can be quantified and visualized with dynamic contrast-enhanced MRI. PET shows metabolism of glucose and accumulation of amyloid and tau, which is useful in showing abnormal metabolism in Alzheimer's disease. Combining MRI and PET allows identification of patients with mixed dementia, with MRI showing white matter injury and PET demonstrating regional impairment of glucose metabolism and deposition of amyloid. Excellent anatomical detail can be observed with 7.0-Tesla MRI. Imaging is the optimal method to follow the effect of treatments since changes in MRI scans are seen prior to those in cognition. This review describes the role of various imaging modalities in the diagnosis and treatment of vascular cognitive impairment.

Lobar intracerebral haematomas: Neuropathological and 7.0-tesla magnetic resonance imaging evaluation.

BACKGROUND AND PURPOSE: The Boston criteria for cerebral amyloid angiopathy (CAA) need validation by neuropathological examination in patients with lobar cerebral haematomas (LCHs). In "vivo" 1.5-tesla magnetic resonance imaging (MRI) is unreliable to detect the age-related signal changes in LCHs. This post-mortem study investigates the validity of the Boston criteria in brains with LCHs and the signal changes during their time course with 7.0-tesla MRI. MATERIALS AND METHODS: Seventeen CAA brains including 26 LCHs were compared to 13 non-CAA brains with 14 LCHs. The evolution of the signal changes with time was examined in 25 LCHs with T2 and T2* 7.0-tesla MRI. RESULTS: In the CAA group LCHs were predominantly located in the parieto-occipital lobes. Also white matter changes were more severe with more cortical microinfarcts and cortical microbleeds. On MRI there was a progressive shift of the intensity of the hyposignal from the haematoma core in the acute stage to the boundaries later on. During the residual stage the hyposignal mildly decreased in the boundaries with an increase of the superficial siderosis and haematoma core collapse. CONCLUSIONS: Our post-mortem study of LCHs confirms the validity of the Boston criteria for CAA. Also 7.0-tesla MRI allows staging the age of the LCHs.

Post-mortem assessment in vascular dementia: advances and aspirations.

BACKGROUND: Cerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease. DISCUSSION: Here, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue. CONCLUSION: Elucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses.

The Topography of Cortical Microinfarcts in Neurodegenerative Diseases and in Vascular Dementia: A Postmortem 7.0-Tesla Magnetic Resonance Imaging Study.

BACKGROUND: Cortical microinfarcts (CoMIs) are considered as barely visible lesions in clinical-neuroradiological correlation studies. On postmortem 7.0-tesla MRI, however, CoMIs of different size are easily detected. SUMMARY: The present MRI study investigates 84 postmortem brains with different neurodegenerative diseases and vascular dementia (VaD) for their topographic distribution and the prevalence of CoMIs. The mean numbers of CoMIs were determined on 6 hemispheric coronal sections and in 22 different gyri with a 7.0-tesla MRI Bruker BioSpin SA. A large coronal section at the level of the mammillary body was also used for neuropathological evaluation. CoMIs were predominantly observed in the prefrontal and postcentral sections of VaD brains. The mean number of CoMIs was significantly increased in the inferior frontal and in the cingulate gyri of VaD brains compared to the controls. No topographic differences were observed in the neurodegenerative diseases. KEY MESSAGES: As the inferior frontal and the cingulated gyri are areas frequently involved in VaD, CoMIs in those strategic locations must have an impact on the evolution of the vascular cognitive decline in those patients.

The incidence of post-mortem neurodegenerative and cerebrovascular pathology in mixed dementia.

BACKGROUND: The clinical picture of dementia in most aged patients is due to a combination of different neurodegenerative processes and frequently associated to cerebrovascular lesions. They are called mixed dementia (MixD) cases, to be differentiated from those with pure vascular dementia (VaD) and those with Alzheimer's dementia (AD). The present study compares the frequency of different associated lesions in these disease groups. MATERIALS AND METHODS: Out of a series of 252 autopsied patients 36 with MixD, 20 with VaD and 64 with AD disease were compared concerning the frequency of the associated lesions. Small cerebrovascular lesions were evaluated on a large coronal section of a cerebral hemisphere. Mean values of frequency and severity were compared between the 3 groups. RESULTS: Of the 120 examined brains 30% were classified as MixD, 17% as VaD and 53% as AD. In 20% of the AD patients Lewy body pathology (LBP) was observed with a low incidence of cerebrovascular lesions, except for cerebral amyloid angiopathy (CAA). The MixD patients had more severe CAA and were significantly older than those with VaD and AD. Lacunar infarcts, on the other hand, were significantly more frequent in the VaD patients. DISCUSSION: The most responsible vascular lesions in MixD and VaD are different. There is an inverse correlation between the presence of LBP and vascular pathology. MixD has to be considered as the end stage of AD.

Topographic distribution of white matter changes and lacunar infarcts in neurodegenerative and vascular dementia syndromes: A post-mortem 7.0-tesla magnetic resonance imaging study.

BACKGROUND: White matter changes and lacunar infarcts are regarded as linked to the same underlying small-vessel pathology. On magnetic resonance imaging, white matter changes are frequently observed, while the number of lacunar infarcts is probably underestimated. The present study post-mortem 7.0-tesla magnetic resonance imaging study compares the severity and the distribution of white matter changes and lacunar infarcts in different neurodegenerative and vascular dementia syndromes in order to determine their impact on the disease evolution. PATIENTS AND METHODS: Eighty-four post-mortem brains consisting of 15 patients with pure Alzheimer's disease and 12 with associated cerebral amyloid angiopathy, 14 patients with frontotemporal lobar degeneration, 7 with Lewy body dementia, 10 with progressive supranuclear palsy, 14 with vascular dementia and 12 control brains were examined. Six hemispheric coronal sections of each brain underwent 7.0-tesla magnetic resonance imaging. Location and severity of white matter changes and lacunar infarcts were evaluated semi-quantitatively in each section separately. RESULTS: White matter changes predominated in the prefrontal and frontal sections of frontotemporal lobar degeneration and in the post-central section of associated cerebral amyloid angiopathy brains, while overall increased in vascular dementia cases. Lacunar infarcts were more frequent in the vascular dementia brains and mainly increased in the centrum semiovale. CONCLUSIONS: White matter changes have a different topographic distribution in neurodegenerative diseases and are most severe and extended in vascular dementia. Lacunar infarcts predominate in the deep white matter of vascular dementia compared to the neurodegenerative diseases. Vascular cognitive impairment is mainly linked to white matter changes due to chronic ischaemia as well as to lacunar infarcts due to small-vessel occlusion.

Detection of Cortical Microbleeds in Postmortem Brains of Patients with Lewy Body Dementia: A 7.0-Tesla Magnetic Resonance Imaging Study with Neuropathological Correlates.

BACKGROUND: It is unclear whether associated cerebrovascular pathology contributes to the clinical spectrum of Lewy body dementia (LBD). SUMMARY: The present postmortem 7.0-tesla MRI study investigates the anatomical distribution of cortical microbleeds (CoMBs) in LBD brains with and without associated Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). CoMBs predominated in the frontal section of the LBD brains and were associated to severe white matter lesions. No differences were observed when LBD brains with and without AD and CAA were compared. KEY MESSAGES: In LBD, there is a specific distribution of CoMBs that is different from that in other neurodegenerative diseases. The increase of frontal CoMBs is not due to the frequently associated AD and CAA features but due to the LBD itself.

The significance of cortical cerebellar microbleeds and microinfarcts in neurodegenerative and cerebrovascular diseases. A post-mortem 7.0-tesla magnetic resonance study with neuropathological correlates.

BACKGROUND: As cortical microbleeds and microinfarcts in neurodegenerative and cerebrovascular diseases have been studied predominantly at the level of the cerebral hemispheres and linked to the presence of cerebral amyloid angiopathy (CAA), we aimed at determining with 7.0-tesla magnetic resonance imaging (MRI) whether the causes and the frequency of cortical cerebellar microbleeds (CCeMBs) and microinfarcts (CCeMIs) are the same. MATERIALS AND METHODS: Hundred and four postmortem brains, composed of 29 with pure Alzheimer's disease (AD), 9 with AD associated to CAA, 10 with frontotemporal lobar degeneration, 9 with amyotrophic lateral sclerosis, 10 with Lewy body disease, 12 with progressive supranuclear palsy, 9 with vascular dementia (VaD), and 16 controls, were examined. On a horizontal section of a cerebellar hemisphere examined with 7.0-tesla MRI, the number CCeMBs and CCeMIs were compared between the different disease groups and the control group. The MRI findings were also compared with the corresponding mean values observed on histological examination of a separate standard horizontal section of a cerebellar hemisphere, used for diagnostic purpose. RESULTS: CCeMBs and CCeMIs were only significantly increased in the VaD group. When comparing the diseased patients with and without CAA mutually and with those with arterial hypertension and severe atherosclerotic cerebrovascular disease, only in the latter an increase of CCeMBs and CCeMIs was observed. There was an excellent correlation between the MRI and the neuropathological findings. CONCLUSIONS: CCeMBs and CCeMIs are mainly due to atherosclerotic cerebrovascular disease and not due to CAA. Their increased presence cannot be included to the Boston diagnostic criteria for CAA.

Prevalence of small cerebral bleeds in patients with progressive supranuclear palsy: a neuropathological study with 7.0-Tesla magnetic resonance imaging correlates.

INTRODUCTION: Progressive supranuclear palsy (PSP) is a degenerative disease affecting mainly the brain stem, basal ganglia and cerebellum. Associated cerebrovascular lesions, mainly small cerebral bleeds, are frequently observed in some neurodegenerative diseases such as Alzheimer dementia and rare in others such as frontotemporal lobar degeneration. The present post-mortem study investigates the prevalence and distribution of small cerebral bleeds in PSP brains. MATERIAL AND METHODS: Nineteen brains of PSP patients were compared to 12 age-matched controls. The prevalence and distribution of mini-bleeds were investigated on a coronal section of a cerebral hemisphere at the level of the mamillary bodies and on a horizontal section through the pons and cerebellum. In addition, out of these series T2*-weighted gradient-echo 7.0-Tesla magnetic resonance imaging (MRI) of 3 coronal sections of a cerebral hemisphere and of a brain stem and cerebellum was performed in 14 PSP and 11 control brains. RESULTS: Although the total number of mini-bleeds was the same on neuropathological examination of both groups, they prevailed around the dentate nucleus of the cerebellum (p = 0.05) and in the tegmentum pontis (p = 0.05) of the PSP brains. On MRI the small bleeds were also more frequent around the dentate nucleus of the cerebellum (p = 0.02) and in the pons (p = 0.04) of PSP brains. DISCUSSION: In PSP brains, mini-bleeds only prevail in the regions affected by the neurodegenerative process, similarly to what happens in frontotemporal lobar degeneration. They should be considered as the result of increased angiogenesis and microglial activation, leading to associated disturbances of the blood-brain barrier in the most affected regions of PSP. They are not indicative of cerebrovascular disease.

Microbleeds in postmortem brains of patients with Alzheimer disease: a T2*-weighted gradient-echo 7.0 T magnetic resonance imaging study.

This study aims to determine the distribution and to quantify microbleeds (MBs) in postmortem brains of patients with Alzheimer disease (AD) on T2*-weighted gradient-echo 7.0 T magnetic resonance imaging. Twenty-eight AD brains were compared with 5 controls. The AD brains were subdivided further: 18 without and 10 with additional severe cerebral amyloid angiopathy (AD-CAA). The distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central, and the occipital level of a cerebral hemisphere. MBs prevailed in the central sections (P=0.005) of AD brains without CAA, whereas in AD-CAA brains, they were more frequent in all coronal sections (P≤0.002). They prevailed in the deep cortical layers of the AD brains and of the controls (P≤0.03). They were significantly increased in all cortical layers of the AD-CAA brains (P≤0.04), compared with the controls. MBs prevalence in brains of AD patients had a different topographic distribution according to the absence or presence of severe CAA.

Prevalence of cerebrovascular lesions in patients with Lewy body dementia: a neuropathological study.

BACKGROUND: The co-existence of vascular pathology in patients with Lewy body dementia (LBD) is still a matter of debate. This study analyses the prevalence and the severity of cerebrovascular lesions in post-mortem brains of patients with LBD. PATIENTS AND METHODS: Twenty brains of demented patients with autopsy-proven Lewy body disease were compared to 14 brains of age-matched controls. RESULTS: Associated Alzheimer disease (AD) features, stages I-IV, were present in 70% of the LBD brains and in 7% of the controls (P<0.001). Cerebral amyloid angiopathy (CAA) was only present in 30% and lipohyalinosis in 10%. A semi-quantitative analysis, performed on a coronal section of a whole cerebral hemisphere and on a horizontal section through the pons and the cerebellum, revealed significantly more mini-bleeds in the LBD brains (P=0.007), predominantly in the cerebral cortex (P=0.03). Other cerebrovascular lesions were only rarely observed. Comparison of the LDB brains, with and without moderate AD features and CAA, showed no difference in the severity of the cerebrovascular lesions including mini-bleeds. CONCLUSIONS: The prevalence of mini-bleeds in LBD brains appears to be independent from the co-existence of moderate AD pathology and CAA. It is more probably due to disturbances of the blood-brain barrier, related to the neurodegenerative process itself.

The significance of small cerebral bleeds in neurodegenerative dementia syndromes.

Small cerebral bleeds are frequently observed in brains of patients with Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). However, they are also observed in patients with other neurodegenerative dementias and in persons without cognitive impairment. The aim of this survey is to compare the bleeding load in brains with different dementia syndromes and in age-matched controls. Hundred sixty-five brains were examined. The prevalence and the severity of the different cerebrovascular lesions were examined. Quantification of the number of mini-bleeds allowed to determinate the bleeding load in different cerebral regions. Micro-bleeds were considered as small macroscopically visible lesions while mini-bleeds were defined as small perivascular accumulations of red blood cells or siderophages only visible on microscopic examination. Several types of cerebrovascular lesions prevailed in AD brains with CAA, compared to the controls. White matter changes prevailed in frontotemporal lobar degeneration. Mini-bleeds were significantly more frequent in the cerebral cortex of AD and Lewy body dementia brains. They also prevailed around the dentate nucleus of the cerebellum and in the tegmentum pontis of patients with progressive supranuclear palsy. On the other hand the bleeding load in frontotemporal lobar degeneration and in corticobasal degeneration was similar to that in age-matched control brains. Cerebrovascular lesions, including micro-bleeds, predominated in AD brains with CAA. Mini-bleeds, on the other hand, were more related to the neurodegenerative process itself and reflected associated disruption of the blood-brain barrier.