Normal ageing of the brain: Histological and biological aspects.

All the hallmarks of ageing are observed in the brain, and its cells, especially neurons, are characterized by their remarkably long lifetime. Like any organ or system, the brain is exposed to ageing processes which affect molecules, cells, blood vessels, gross morphology and, uniquely for this organ, cognition. The preponderant cerebral structures are characterized by the cellular processes of neurons and glial cells and while the quantity of cerebral interstitial fluid is limited, it is now recognized as playing a crucial role in maintaining cerebral homeostasis. Most of our current knowledge of the ageing brain derives from studies of neurodegenerative disorders. It is interesting to note that common features of these disorders, like Tau, phosphoTau and amyloid peptide accumulation, can begin relatively early in life as a result of physiological ageing and are present in subclinical cases while also being used as early-stage markers of neurodegenerative diseases in progression. In this article, we review tissue and cellular modifications in the ageing brain. Commonly described macroscopic, microscopic and vascular changes that in the ageing brain are contrasted with those seen in neurodegenerative contexts. We also review the molecular changes that occur with age in the brain, such as modifications in gene expression, insulin/insulin-like growth factor 1 signalling dysfunction, post-translational protein modifications, mitochondrial dysfunction, autophagy and calcium conductance changes.

Alcohol and psychotropic drugs: risk factors for orthostatic hypotension in elderly fallers.

We assess orthostatic hypotension (OH) prevalence in elderly fallers and determine OH-associated risk factors in this patient population. A monocentric prospective study at Lille University Hospital Falls Clinic included 833 consecutive patients who had fallen or were at high risk of falls and who were assessed for the presence of OH. Among 833 patients aged 80.4±7.4 years, OH was found in 199 subjects (23.9% of cases). Multivariate analysis showed that selective serotonin reuptake inhibitors (odds ratio (OR) 2.42, 95% confidence interval (CI): 1.56-3.75), serotonin-norepinephrine reuptake inhibitors (OR 5.37, 95% CI: 1.93-14.97), Parkinsonian syndrome (OR 2.54, 95% CI: 1.54-4.19), excessive alcohol consumption (OR 2.17, 95% CI: 1.32-3.56), meprobamate (OR 2.65, 95% CI: 1.12-6.25) and calcium channel blockers (OR 1.79, 95% CI: 1.16-2.76) were all risk factors for OH. In contrast, angiotensin receptor blockers (OR 0.52, 95% CI: 0.30-0.91) appeared to be protective factors against OH. This study demonstrates that a systematic investigation should be made in all elderly fallers and those at high risk of falls to detect the presence of OH. In OH patients, in addition to the usual predisposing factors, excessive alcohol consumption and psychotropic drug intake-in particular, the intake of serotonergic antidepressants-should be taken into account as potential risk factors.

The topography of cortical microbleeds in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance study.

INTRODUCTION: Cerebrovascular lesions are rare in frontotemporal lobar degeneration (FTLD), in contrast to other neurodegenerative diseases. Cortical microbleeds (CoMBs) are frequent in Alzheimer's disease, in particular in cases associated with cerebral amyloid angiopathy. The present study investigates the gyral topographic distribution of CoMBs in post-mortem FTLD brains with 7.0-tesla magnetic resonance imaging. MATERIAL AND METHODS: The distribution of CoMBs in 11 post-mortem FTLD brains and in 12 control brains was compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean values of CoMBs were determined in twenty-two different gyri. The findings were correlated to those separately observed on neuropathological examination. RESULTS: As a whole there was a trend of more CoMBs in the prefrontal section of FTLD as well as of the control brains. CoMBs were significantly increased in the superior frontal gyrus and the insular cortex (p ≤ 0.001) and also in the inferior frontal gyrus and the superior temporal gyrus (p ≤ 0.01). CONCLUSIONS: CoMBs in FTLD are only increased in the regions mainly affected by the neurodegenerative lesions. They probably do not reflect additional cerebrovascular disease.

Topography of Cortical Microbleeds in Alzheimer's Disease with and without Cerebral Amyloid Angiopathy: A Post-Mortem 7.0-Tesla MRI Study.

Cortical microbleeds (CMBs) detected on T2*-weighted gradient-echo (GRE) magnetic resonance imaging (MRI) are considered as a possible hallmark of cerebral amyloid angiopathy (CAA). The present post-mortem 7.0-tesla MRI study investigates whether topographic differences exist in Alzheimer's brains without (AD) and with CAA (AD-CAA). The distribution of CMBs in thirty-two post-mortem brains, consisting of 12 AD, 8 AD-CAA and 12 controls, was mutually compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean numbers of CMBs were determined in twenty-two different gyri. As a whole there was a trend of more CMBs on GRE MRI in the prefrontal section of the AD, the AD-CAA as well as of the control brains. Compared to controls AD brains had significantly more CMBs in the superior frontal, the inferior temporal, the rectus and the cinguli gyrus, and in the insular cortex. In AD-CAA brains CMBs were increased in all gyri with exception of the medial parietal gyrus and the hippocampus. AD-CAA brains showed a highly significant increase of CMBs in the inferior parietal gyrus (p value: 0.001) and a significant increase in the precuneus and the cuneus (p value: 0.01) compared to the AD brains. The differences in topographic distribution of CMBs between AD and AD-CAA brains should be further investigated on MRI in clinically suspected patients.

Brain Magnetic Susceptibility Changes in Patients with Natalizumab-Associated Progressive Multifocal Leukoencephalopathy.

We investigated the brain magnetic susceptibility changes induced by natalizumab-associated progressive multifocal leukoencephalopathy. We retrospectively included 12 patients with natalizumab-progressive multifocal leukoencephalopathy, 5 with progressive multifocal leukoencephalopathy from other causes, and 55 patients with MS without progressive multifocal leukoencephalopathy for comparison. MR imaging examinations included T2* or SWI sequences in patients with progressive multifocal leukoencephalopathy (86 examinations) and SWI in all patients with MS without progressive multifocal leukoencephalopathy. Signal abnormalities on T2* and SWI were defined as low signal intensity within the cortex and/or U-fibers and the basal ganglia. We observed T2* or SWI signal abnormalities at the chronic stage in all patients with progressive multifocal leukoencephalopathy, whereas no area of low SWI signal intensity was detected in patients without progressive multifocal leukoencephalopathy. Among the 8 patients with asymptomatic natalizumab-progressive multifocal leukoencephalopathy, susceptibility changes were observed in 6 (75%). The basal ganglia adjacent to progressive multifocal leukoencephalopathy lesions systematically appeared hypointense by using T2* and/or SWI. Brain magnetic susceptibility changes may be explained by the increased iron deposition and constitute a useful tool for the diagnosis of progressive multifocal leukoencephalopathy.

Post-mortem 7.0-tesla magnetic resonance study of cortical microinfarcts in neurodegenerative diseases and vascular dementia with neuropathological correlates.

BACKGROUND: Until recently cortical microinfarcts (CMIs) were considered as the invisible lesions in clinical-radiological correlation studies that rely on conventional structural magnetic resonance imaging. The present study investigates the presence of CMIs on 7.0-T magnetic resonance imaging (MRI) in post-mortem brains with different neurodegenerative and cerebrovascular diseases. MATERIALS AND METHODS: One hundred-seventy five post-mortem brains, composed of 37 with pure Alzheimer's disease (AD), 12 with AD associated to cerebral amyloid angiopathy (AD-CAA), 38 with frontotemporal lobar degeneration, 12 with amyotrophic lateral sclerosis, 16 with Lewy body disease (LBD), 21 with progressive supranuclear palsy, 18 with vascular dementia (VaD) and 21 controls were examined. According to their size several types of CMIs were detected on 3 coronal sections of a cerebral hemisphere with 7.0-T MRI and compared to the mean CMI load observed on histological examination of one standard separate coronal section of a cerebral hemisphere at the level of the mamillary body. RESULTS: Overall CMIs were significantly prevalent in those brains with neurodegenerative and cerebrovascular diseases associated to CAA compared to those without CAA. VaD, AD-CAA and LBD brains had significantly more CMIs compared to the controls. While all types of CMIs were increased in VaD and AD-CAA brains, a predominance of the smallest ones was observed in the LBD brains. CONCLUSIONS: The present study shows that 7.0-T MRI allows the detection of several types of MICs and their contribution to the cognitive decline in different neurodegenerative and cerebrovascular diseases.

Iron deposits in post-mortem brains of patients with neurodegenerative and cerebrovascular diseases: a semi-quantitative 7.0 T magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Accumulation of iron (Fe) is often detected in brains of people suffering from neurodegenerative diseases. However, no studies have compared the Fe load between these disease entities. The present study investigates by T2*-weighted gradient-echo 7.0 T magnetic resonance imaging (MRI) the Fe content in post-mortem brains with different neurodegenerative and cerebrovascular diseases. METHODS: One hundred and fifty-two post-mortem brains, composed of 46 with Alzheimer's disease (AD), 37 with frontotemporal lobar degeneration (FTLD), 11 with amyotrophic lateral sclerosis, 13 with Lewy body disease, 14 with progressive supranuclear palsy, 16 with vascular dementia (VaD) and 15 controls without a brain disease, were examined. The Fe load was determined semi-quantitatively on T2*-weighted MRI serial brain sections in the claustrum, caudate nucleus, putamen, globus pallidus, thalamus, subthalamic nucleus, hippocampus, mamillary body, lateral geniculate body, red nucleus, substantia nigra and dentate nucleus. The disease diagnosis was made on subsequent neuropathological examination. RESULTS: The Fe load was significantly increased in the claustrum, caudate nucleus and putamen of FTLD brains and to a lesser degree in the globus pallidus, thalamus and subthalamic nucleus. In the other neurodegenerative diseases no Fe accumulation was observed, except for a mild increase in the caudate nucleus of AD brains. In VaD brains no Fe increase was detected. CONCLUSIONS: Only FTLD displays a significant Fe load, suggesting that impaired Fe homeostasis plays an important role in the pathogenesis of this heterogeneous disease entity.

Superficial siderosis of the central nervous system: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

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.

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

Vascular neuropathology and cognitive decline.

Cerebrovascular disease is an important cause of cognitive decline and dementia. Despite numerous epidemiological, clinical, neuroimaging and neuropathological studies, the link between cerebrovascular lesions and their impact on cognition and behavior is still a matter of debate. Cerebrovascular lesions are heterogeneous and most descriptive studies distinguish vessel wall modifications, perivascular space modifications, white matter changes, and infarcts as the main features of vascular dementia. However, to date there is still no consensual criteria for the neuropathological diagnosis of vascular or mixed dementia. The diagnosis of these conditions still relies on both clinical and neuropathological expertise.

Detection of microbleeds in post-mortem brains of patients with frontotemporal lobar degeneration: a 7.0-Tesla magnetic resonance imaging study with neuropathological correlates.

BACKGROUND: Microbleeds (MBs) are frequently detected in brains of patients with Alzheimer dementia and rare in those with frontotemporal lobar degeneration (FTLD). This study investigates for the first time the topographic distribution of MBs on a T2*-weighted gradient-echo 7.0-T magnetic resonance imaging (MRI) in post-mortem FTLD brains. PATIENTS AND METHODS: The neuropathological and MRI findings in 12 FTLD brains were compared with eight age-matched controls. The presence of cerebrovascular lesions was evaluated on a coronal section of a cerebral hemisphere at the level of the mamillary body and on a horizontal section through pons and cerebellum. On MRI, 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. RESULTS: Overall, cerebrovascular lesions were rare. Only white matter damage was significantly more severe in FTLD brains compared with controls (P = 0.03). On MRI, MBs were only significantly prevalent in the deep cortical layers (P < 0.01) and borderline increased in the middle cortical layers (P = 0.07) of the frontal section. CONCLUSIONS: Cerebrovascular lesions are rare in FTLD. The white matter damage has to be considered as part of the neurodegenerative process. MBs prevail in the frontal regions with the most severe neuronal damage and probably represent associated disruption of the blood-brain barrier.

Cerebrovascular lesions in patients with frontotemporal lobar degeneration: a neuropathological study.

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.

Staging and natural history of cerebrovascular pathology in dementia.

OBJECTIVE: Most pathologic studies indicate that significant vascular changes are found in the majority of elderly persons, either alone or in association with neurodegenerative processes such as Alzheimer disease (AD) or dementia with Lewy bodies (DLB). Cumulative burden of cerebrovascular lesions can explain cognitive decline described as vascular cognitive impairment, but because there is a lack of consensus in the best way to quantify vascular pathology, the relationship between cognitive decline and cerebrovascular disease remains uncertain. We developed a rating scheme for cerebrovascular lesions using postmortem brains from patients with dementia from 2 European tertiary care memory clinics. METHODS: A total of 135 brains with a neuropathologic diagnosis of vascular dementia (VaD) (n = 26), AD + VaD (n = 39), DLB + VaD (n = 21), AD + DLB + VaD (n = 9), AD (n = 19), and DLB (n = 21) were investigated in this study. Cerebrovascular lesions were rated on large sections from the hippocampus, the temporal lobe, the frontal lobe, and basal ganglia. RESULTS: In patients with dementia, vessel wall modifications such as arteriolosclerosis or amyloid angiopathy are the most common and presumably the earliest changes. Modifications in perivascular spaces and myelin loss are the next most common. Lacunar or regional infarcts may occur as a consequence of an independent process or in the final phase of small vessel diseases. CONCLUSION: A staging system based on this conceptual model of cerebrovascular pathology could enable the neuropathologic quantification of the cerebrovascular burden in dementia. Further studies are needed to determine whether this system can be used in large-scale studies to understand clinical-cerebrovascular pathologic correlations.

Hippocampal microbleed on a post-mortem t(2)∗-weighted gradient-echo 7.0-tesla magnetic resonance imaging?

The present post-mortem study of a brain from an Alzheimer patient showed on a T(2)∗-weighted gradient-echo 7.0-T MRI of a coronal brain section a hyposignal in the hippocampus, suggesting a microbleed. On the corresponding histological examination, only iron deposits around the granular cellular layer and in blood vessel walls of the hippocampus were observed without evidence of a bleeding. This case report illustrates that the detection of microbleeds on MRI has to be interpreted with caution.

Mis-splicing of Tau exon 10 in myotonic dystrophy type 1 is reproduced by overexpression of CELF2 but not by MBNL1 silencing.

Tau is the proteinaceous component of intraneuronal aggregates common to neurodegenerative diseases called Tauopathies, including myotonic dystrophy type 1. In myotonic dystrophy type 1, the presence of microtubule-associated protein Tau aggregates is associated with a mis-splicing of Tau. A toxic gain-of-function at the ribonucleic acid level is a major etiological factor responsible for the mis-splicing of several transcripts in myotonic dystrophy type 1. These are probably the consequence of a loss of muscleblind-like 1 (MBNL1) function or gain of CUGBP1 and ETR3-like factor 1 (CELF1) splicing function. Whether these two dysfunctions occur together or separately and whether all mis-splicing events in myotonic dystrophy type 1 brain result from one or both of these dysfunctions remains unknown. Here, we analyzed the splicing of Tau exons 2 and 10 in the brain of myotonic dystrophy type 1 patients. Two myotonic dystrophy type 1 patients showed a mis-splicing of exon 10 whereas exon 2-inclusion was reduced in all myotonic dystrophy type 1 patients. In order to determine the potential factors responsible for exon 10 mis-splicing, we studied the effect of the splicing factors muscleblind-like 1 (MBNL1), CUGBP1 and ETR3-like factor 1 (CELF1), CUGBP1 and ETR3-like factor 2 (CELF2), and CUGBP1 and ETR3-like factor 4 (CELF4) or a dominant-negative CUGBP1 and ETR-3 like factor (CELF) factor on Tau exon 10 splicing by ectopic expression or siRNA. Interestingly, the inclusion of Tau exon 10 is reduced by CUGBP1 and ETR3-like factor 2 (CELF2) whereas it is insensitive to the loss-of-function of muscleblind-like 1 (MBNL1), CUGBP1 and ETR3-like factor 1 (CELF1) gain-of-function, or a dominant-negative of CUGBP1 and ETR-3 like factor (CELF) factor. Moreover, we observed an increased expression of CUGBP1 and ETR3-like factor 2 (CELF2) only in the brain of myotonic dystrophy type 1 patients with a mis-splicing of exon 10. Taken together, our results indicate the occurrence of a mis-splicing event in myotonic dystrophy type 1 that is induced neither by a loss of muscleblind-like 1 (MBNL1) function nor by a gain of CUGBP1 and ETR3-like factor 1 (CELF1) function but is rather associated to CUGBP1 and ETR3-like factor 2 (CELF2) gain-of-function.

Comparison of 7.0-T T2*-magnetic resonance imaging of cerebral bleeds in post-mortem brain sections of Alzheimer patients with their neuropathological correlates.

BACKGROUND: In view of the increasing recognition of cerebral microbleeds (MCBs) with MRI, there is a need to validate their detection in post-mortem brains in patients with cerebrovascular diseases and dementia. MATERIALS AND METHODS: Out of 20 post-mortem brains of patients with Alzheimer dementia and with different cerebrovascular lesions, 45 large sections of the cerebral hemispheres, brainstem and cerebellum were submitted to a 7.0-T T2*-weighted MRI, and afterwards compared to the histological detection of haematomas, MCBs and mini-bleeds (MNBs). RESULTS: The sensitivity, specificity, predictive positive value and predictive negative value of the T2* imaging to detect MCBs and MNBs were excellent for those in the cortico-subcortical regions. There was a significant overestimation of MNBs in the striatum due to iron deposits unrelated to old haemorrhages. Also in the deep white matter, 42% of MNBs were not detected, while 31% of T2* hyposignals were not due to MNBs but to vessels filled with post-mortem thrombi. CONCLUSIONS: When evaluating the 'bleeding load' with 7.0-T T2*-weighted MRI in post-mortem brain sections of patients with dementia and vascular risk factors, only quantification of small cerebral bleeds in the cortico-subcortical regions is reliable.

The impact of cerebral amyloid angiopathy on the occurrence of cerebrovascular lesions in demented patients with Alzheimer features: a neuropathological study.

OBJECTIVE: The aim of this neuropathological study was to determine the prevalence of the different cerebrovascular lesions to be attributed to cerebral amyloid angiopathy (CAA) and of those associated with the severity of the Alzheimer dementia (AD) itself. PATIENTS AND METHODS: The cerebrovascular lesions were compared separately in 40 brains of patients with mild and 50 with severe AD features. In the two groups, the number of lesions were compared between the brains with severe and those with mild of absent CAA. RESULTS: The age of the patients, the vascular risk factors and antithrombotic treatment were similar in all the compared groups. The brains with mild and severe AD features and with CAA contained more haematomas, cortical micro-infarcts and micro-bleeds, and more severe white matter changes, and cortico-subcortical and white matter mini-bleeds. In the CAA brains with severe AD features, also more cortical territorial infarcts were observed, compared to those with mild AD features. CONCLUSIONS: The increase in cortical infarcts cannot be attributed to the CAA alone, but also to the severity of the degenerative features, implying additional vascular factors in the pathogenesis of AD.

Prediction of pathology in primary progressive language and speech disorders.

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) encompasses a variety of clinicopathologic entities. The antemortem prediction of the underlying pathologic lesions is reputed to be difficult. This study sought to characterize correlations between 1) the different clinical variants of primary progressive language and speech disorders and 2) the pathologic diagnosis. METHODS: The latter was available for 18 patients having been prospectively monitored in the Lille Memory Clinic (France) between 1993 and 2008. RESULTS: The patients were diagnosed with progressive anarthria (n = 5), agrammatic progressive aphasia (n = 6), logopenic progressive aphasia (n = 1), progressive jargon aphasia (n = 2), typical semantic dementia (n = 2), and atypical semantic dementia (n = 2). All patients with progressive anarthria had a tau pathology at postmortem evaluation: progressive supranuclear palsy (n = 2), Pick disease (n = 2), and corticobasal degeneration (n = 1). All patients with agrammatic primary progressive aphasia had TDP-43-positive FTLD (FTLD-TDP). The patients with logopenic progressive aphasia and progressive jargon aphasia had Alzheimer disease. Both cases of typical semantic dementia had FTLD-TDP. The patients with atypical semantic dementia had tau pathologies: argyrophilic grain disease and corticobasal degeneration. CONCLUSIONS: The different anatomic distribution of the pathologic lesions could explain these results: opercular and subcortical regions in tau pathologies with progressive anarthria, the left frontotemporal cortex in TDP-43-positive frontotemporal lobar degeneration (FTLD-TDP) with agrammatic progressive aphasia, the bilateral lateral and anterior temporal cortex in FTLD-TDP or argyrophilic grain disease with semantic dementia, and the left parietotemporal cortex in Alzheimer disease with logopenic progressive aphasia or jargon aphasia. These correlations have to be confirmed in larger series.

[Neurological diseases detected in the Lille Multidisciplinary Falls Consultation]. / Les maladies neurologiques repérées lors de la consultation multidisciplinaire de la chute du CHRU de Lille (France).

BACKGROUND: People with neurological disorders including stroke, dementia, Parkinson's disease, and polyneuropathy are known to have an increased risk of falls. OBJECTIVE: To evaluate the prevalence and nature of neurological risk factors among the patients attending the Multidisciplinary Falls Consultation of the University Hospital of Lille (France), and to analyze the characteristic features of patients termed "neurological fallers" with neurological risk factors. METHODS: The study included 266 consecutive patients who were initially assessed by a geriatrician, a neurologist and a physiatrist, and again, six months later, by the same geriatrician. RESULTS: Two out of three patients had neurological signs that can be regarded as neurological risk factors of falling. These neurological signs had not been diagnosed before the consultation in 85% of cases. The most common conditions were deficit of lower extremity proprioception (59% of patients) and cognitive impairment (43%). The most frequently evoked neurological diseases were dementia (40% of patients), polyneuropathy (17%) and stroke (8%). Compared with other patients, "neurological fallers" were more frequently living in a nursing home, had lower ADL and MMSE scores at baseline, had experienced more falls in the six preceding months, had a lower probability of having a timed Up-and-Go test less than 20 seconds and a single limb stance equal to 5 seconds. In the follow-up, "neurological fallers" reported hospitalizations more often. CONCLUSION: The findings show that a large proportion of old persons presenting at the Multidisciplinary Falls Consultation have unrecognized neurological disorders. Comprehensive neurological examination including an evaluation of cognition is required in every elderly faller.