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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.

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.

Aims: We investigated the performance in scene categorization of patients with Alzheimer's disease (AD) using a saccadic choice task. Method: 24 patients with mild AD, 28 age-matched controls and 26 young people participated in the study. The participants were presented pairs of coloured photographs and were asked to make a saccadic eye movement to the picture corresponding to the target scene (natural vs. urban, indoor vs. outdoor). Results: The patients' performance did not differ from chance for natural scenes. Differences between young and older controls and patients with AD were found in accuracy but not saccadic latency. Conclusions: The results are interpreted in terms of cerebral reorganization in the prefrontal and temporo-occipital cortex of patients with AD, but also in terms of impaired processing of visual global properties of scenes.

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.

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.

Background: Superficial siderosis (SS) is a rare finding on T2*-weighted magnetic resonance imaging (MRI), regarded as a radiological marker of cerebral amyloid angiopathy (CAA). The present study investigates with 7.0-tesla MRI the prevalence of SS and its underlying pathological substrate in a consecutive series of post-mortem brains of elderly patients with various neurodegenerative and cerebrovascular lesions. Materials and Methods: The prevalence of SS and associated lesions was screened using 7.0-tesla MRI and their neuropathological correlates in 120 post-mortem brains of patients with various neurodegenerative and cerebrovascular diseases. Results: Eighty-three separate zones of SS were detected in 45 brains (37.5%), including 25 areas of disseminated SS (dSS) and 58 areas of focal SS (fSS), restricted to less than 3 sulci. dSS was spatially related to sequels of 14 lobar haematomas and 11 cerebral infarcts, while fSS was connected to 19 microbleeds and 39 micro-infarcts (p < 0.001). Comparison of the 15 CAA to the 30 non-CAA brains showed that dSS was due to an old lobar haematoma in 53% of the former group compared to 3% of the latter group (p = 0.003). fSS was due to a microbleed in 7% of the CAA brains and to 40% of the non-CAA brains (p = 0.03). Conclusions: SS is associated with both haemorrhagic and ischaemic underlying lesions. It is frequently observed on T2*-weighted 7.0-tesla MRI, and two types of SS may be described. Clinicians should keep in mind that SS may be found in other settings than CAA.

Background: Cerebrovascular lesions are frequently observed in Alzheimer brains. Not all of them are due to cerebral amyloid angiopathy. Some of them are related to the severity of the degenerative process itself, implying additional vascular factors in the pathogenesis of Alzheimer’s dementia. The aim of the study was to investigate the impact of cerebrovascular pathology on brains with frontotemporal lobar degeneration (FTLD). Patients and Methods: Twenty-two brains with autopsy-proven FTLD were compared to 15 brains of age-matched patients without evident cognitive decline, who died from an illness not related to a brain disease. The prevalence and the severity of small ischaemic and haemorrhagic lesions were determined. Vascular risk factors and the use of antithrombotic agents were also recorded. Results: The patients with FTLD were heterogeneous concerning age of onset, disease duration, clinical presentation, genetic background and neuropathological typing. Cerebrovascular risk factors and lesions were overall rare in FTLD brains without differences in their prevalence and severity compared to the controls. Only white matter changes were more prevalent in the FTLD group (p = 0.04) and showed a trend to greater severity (p = 0.08). Conclusions: Cerebrovascular pathology is not contributing to the evolution of the disease process of patients with FTLD. The isolated prevalence of white matter changes should not be considered as a vascular indicator.

Background/Aims: Our purpose was to analyze consultations with primary- and secondary-care physicians by demented people and identify factors that hamper or facilitate consultation. Methods: In total, 498 demented subjects were evaluated within the Three-City Study, a population-based cohort of individuals aged ≧65 years.Primary- and secondary-care consultations (consultation with a specialist and/or treatment with anti-dementia drugs) were assessed by a neurologist or geriatrician. Results: Thirty-five percent of the demented subjects did not seek advice for their cognitive problems and only 31% consulted a specialist. Consultation for primary care was principally dependent on the subjects’ own awareness of the cognitive disorder and on their age. Factors associated with consultation for secondary care were younger age, higher education level, higher instrumental activities of daily living disability and awareness of the cognitive disorder by the subject, all of which predicted more frequent consultation. The level of cognitive performance had only a slight influence on primary care and none on secondary care. Conclusion: The failure to see a physician due to dementia, especially secondary-care practitioners, is frequent in the community, particularly in the oldest subjects.

Frontotemporal dementia (FTD) is a neurodegenerative disease characterised by behavioural disorders that suggest abnormalities of emotional processing. In a previous study, we showed that patients with Alzheimer’s disease (AD) and with FTD were equally able to distinguish a face displaying affect from one not displaying affect. However, recognition of emotion was worse in patients with FTD than in patients with AD who did not differ significantly from controls. The aim of this study was to follow up the perception of emotions on faces in these patients. The poor perception of emotion could worsen differently in AD and in FTD, with the progression of atrophy of the amygdala, the anterior temporal cortex and the orbital frontal cortex, structures that are components of the brain’s emotional processing systems. Methods: Patients with AD or with FTD had to recognise and point out the name of one of seven basic emotions (anger, disgust, happiness, fear, sadness, surprise and contempt) on a set of 28 faces presented on slides at the first visit and 3 years later. Results: Thirty-seven patients (AD = 19, FTD = 18) performed the tests initially. The two patient groups did not differ for age, sex and duration of the disease. During the follow-up, 12 patients died, 4 patients refused to perform the tests and 8 could not be tested because of the severity of the disease. Finally, 7 patients with AD and 6 patients with FTD performed the two tests at a mean delay of 40 months. All patients with AD had worse results at follow-up on the perception of emotion despite the prescription of inhibitors of cholinesterase in all patients and of selective serotonin reuptake inhibitors (SSRIs) in 4 patients. As a whole, patients with FTD had better results in the second than in the first assessment (however, 3 of them had worse results) independently of the prescription of trazodone (n = 2), other SSRIs (n = 2), or the absence of treatment (n = 2), and of possible cognitive change. Conclusions: Recognition of emotion on faces in AD decreases with the progression of dementia and could be related to the progression of the degeneration of the structures implicated in emotional processing systems. Inconsistency of the results in FTD may be related to impulsiveness, lack of consistency of the patients and to heterogeneity of the progression of the lesions.

Introduction: Frontotemporal dementia (FTD) is a more common cause of dementia than previously recognised. Few data are available regarding the natural course of FTD in terms of survival, nursing home admission and causes of death. Methods: An observational study of all consecutive patients referred to the memory centre of Lille, France, between 1995 and 1999, and examined at least twice in this centre, with a diagnosis of FTD (frontal or behavioural variant) or of Alzheimer’s disease (AD) was performed. Kaplan-Meyer analysis allowing for delayed entry was used to compare the survival functions in FTD and AD. Results: 552 patients were included, of whom 49 (8.9%) were lost to follow-up at 3 years. FTD patients were younger (mean age at onset 59 years), had more often a family history of psychiatric disorders (20%), had a longer delay between first symptoms and first visit (5.9 years) and a higher Mini-Mental State Examination (MMSE) score at first visit (24.5) than patients with AD (19.9). The mean annual MMSE score decline was 0.9 point in FTD vs. 2.0 points in AD (p < 0.0004). Fewer patients with FTD than with AD entered an institution (RR: 0.20, 95% CI 0.05–0.81). After adjustment for sex, age at first visit, level of education and MMSE score at first visit, survival rates in FTD and AD did not differ significantly. Patients with FTD often had a sudden death, the cause of which could not be found. The earlier the first visit after onset, the longer the survival rate, whatever the diagnosis (RR: 0.76, 95% CI 0.67–0.86, p < 0.0001 per year of earlier first visit). Conclusion: This large study showed that the mean duration of FTD was 2 years longer than that of AD, but the risk of death after adjustment for age and sex was similar in FTD and in AD. Sudden and unexplained causes of death were frequent and need further study. Early management increases the life span of demented patients.

Since the recognition of white matter changes on CT (leukoaraiosis), rating scales for the location and severity of white matter changes have been developed, mainly for research purposes, to investigate factors such as the relation with cognition, risk factors, and pathology. The main purpose of rating scales is to provide scores that can be used in statistical analyses. The development of the NINDS-AIREN criteria for vascular dementia have introduced a new application for these rating scales in investigating and delineating the amount of white matter changes on CT/MRI sufficient to fulfill the criteria. Furthermore, in Alzheimer’s disease, recognition of white matter changes may serve to delineate homogeneous groups and help to identify patients with different symptomatology. We reviewed the existing rating scales for CT and MRI and judged their properties and reliability. The ideal rating scale does not yet exist, but different rating scales may serve different purposes, for which some recommendations are made.

In our memory clinic experience, memory impairment differs widely in patients with frontotemporal dementia (FTD). We searched for a correlation between explicit memory disturbance assessed with the Grober and Buschke test and medial temporal atrophy on CT scan in 22 consecutive patients with FTD. Five of the 22 patients had a medial temporal lobe (MTL) atrophy. There was no significant difference between the two groups for the demographic characteristics. Free recall, cued recall and the learning curve were significantly better in patients without MTL atrophy. The patients with MTL atrophy made more intrusions. We found a positive correlation between total recall and cued recall and the mean of medial temporal lobe measurement. These results are in agreement with the role of the hippocampal formation in the memory process. In our group, the ratio of patients with MTL atrophy is similar to the ratio of Pick’s disease in frontotemporal dementia. In histological series more severe hippocampal atrophy are reported in Pick’s disease. Therefore MTL atrophy on CT scan could be a marker of Pick’s disease in FTD.

A double-blind, placebo-controlled, parallel-group, multicentre study was conducted to evaluate the efficacy of pentoxifylline (Trental) in patients with multi-infarct dementia (MID) according to DSM-III-R criteria. Men and women aged 45 years or older, with a Hachinski Ischemia Scale scoreor = 7 and a Mini Mental State Examination (MMSE) score of 10-25 at entry, and computed tomographic evidence of vascular disease were enrolled. A total of 289 patients were randomised to receive either oral pentoxifylline 400 mg t.i.d. or placebo for 9 months, and efficacy was assessed every 3 months. The primary outcome variable was the difference in scores between the two treatment groups, as measured on the Gottfries, Bråne, Steen (GBS) scale. Secondary outcome variables included the scores achieved on the Sandoz Clinical Assessment Geriatric (SCAG) scale and MMSE, and a battery of psychological and other tests. The intention-to-treat analysis for patients completing the study (n = 239) showed a statistically significant difference in the total GBS score in favour of pentoxifylline (improvement of 3.5 points, p = 0.028). A significant difference in the total GBS score in favour of pentoxifylline was even almost achieved in the intention-to-treat analysis for all evaluable patients (n = 269, improvement of 2.1 points, p = 0.065). It is concluded that treatment with pentoxifylline is beneficial for patients with MID, the global results of the GBS and SCAG scales being reinforced by significant improvements in those subscales specific for intellectual and cognitive function.

Capgras' delusion (CD) may be secondary to a neurologic lesion, particularly in the right frontal or occipital regions. A 40-year-old woman with multiple sclerosis underwent SPECT during and after an episode of CD. Analysis during delusion showed an uptake defect in the right parietal cortex with an 11% index of asymmetry (normal:or = 4%). Post-delusion SPECT showed decreased bifrontal and biparietal cortical uptake indices but a normal index of asymmetry. Functional brain imaging may provide clues to the psychopathology of CD.