Alzheimer Disease: Leys D

Leys D, Pasquier F. · No affiliation provided · Stroke. · Pubmed #15073393 links to  free full text

This publication has no abstract.

Pasquier F, Boulogne A, Leys D, Fontaine P. · Department of Neurology, EA 2691, Memory Clinic, Lille, France. · Diabetes Metab. · Pubmed #17110895 links to  free full text

Abstract: Alzheimer's disease (AD) and diabetes mellitus (DM) are two of the most common and devastating health problems in the elderly. They share a number of common features amongst which high prevalence after 65 years, important impact of patient's quality of life, substantial health care costs. Reviews on the epidemiological studies on cognitive impairment in patients with DM found evidence of cross-sectional and prospective associations between type 2 DM and moderate cognitive impairment, on memory and executive functions. There is also evidence for an elevated risk of both vascular dementia and AD in patients with type 2 DM, albeit with strong interaction of other factors such as hypertension, dyslipidaemia and ApoE genotype. DM is an independent predictor of post-stroke dementia. DM being an atherogenic risk factor, it may increase the risk of dementia through associations with stroke, causing vascular dementia. In addition, vascular reactivity may be adversely affected by advanced glycosylation end products resulting in more subtle perfusion abnormalities. Cerebrovascular disease may exacerbate AD through direct interactions between the two pathological processes or through cognitive impairment secondary to cerebrovascular disease "unmasking" AD at an earlier stage than it would otherwise become apparent. The increased risk of AD may also be mediated by the exacerbation of B-amyloid neurotoxicity by advanced glycosylation end products identified in the matrix of neurofibrillary tangles and amyloid plaques in AD brains, or associations with insulin functions. Decreased cholinergic transport across the blood-brain barrier observed in diabetic animals may exacerbate cognitive impairment in AD. Many interventions could reduce the cognitive decline associated with DM, yet not enough are taken into account so far.

Leys D, Hénon H, Mackowiak-Cordoliani MA, Pasquier F. · Stroke department, Department of Neurology, University of Lille II, EA 2691, Rue Emile Laine, Lille, France. · Lancet Neurol. · Pubmed #16239182 No free full text.

Abstract: Dementia is one of the major causes of dependency after stroke. The prevalence of poststroke dementia (PSD)-defined as any dementia occurring after stroke-is likely to increase in the future. In community-based studies, the prevalence of PSD in stroke survivors is about 30% and the incidence of new onset dementia after stroke increases from 7% after 1 year 48% after 25 years. Having a stroke doubles the risk of dementia. Patient-related variables associated with an increased risk of PSD are increasing age, low education level, dependency before stroke, prestroke cognitive decline without dementia, diabetes mellitus, atrial fibrillation, myocardial infarction, epileptic seizures, sepsis, cardiac arrhythmias, congestive heart failure, silent cerebral infarcts, global and medial-temporal-lobe atrophy, and white-matter changes. Stroke-related variables associated with an increased risk of PSD are stroke severity, cause, location, and recurrence. PSD might be the result of vascular lesions, Alzheimer pathology, white-matter changes, or combinations of these. The cause of PSD differs among studies in relation to the mean age of patients, ethnicity, criteria used, and time after stroke. In developed countries, the proportion of patients with presumed Alzheimer's disease among those with PSD is between 19% and 61%. Patients with PSD have high mortality rates and are likely to be functionally impaired. These patients should be treated according to the current guidelines for stroke prevention.

Hanon O, Leys D. · Department of Geriatrics, Hôspital Broca, Paris, France. · J Renin Angiotensin Aldosterone Syst. · Pubmed #12428218 No free full text.

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Masson C, Leys D, Buée L. · Service de Neurologie, Hôpital Beaujon, Clichy. · Presse Med. · Pubmed #11094619 No free full text.

Abstract: PATHOLOGY FINDINGS: Cerebral amyloid angiopathies are defined by the presence of amyloid deposits on the walls of cerebral vessels. These amyloid deposits are found in the media of arterioles of the leptomeninges and the cortex. They are sometimes associated with Alzheimer-type lesions. Overt amyloid vasculopathy characterized by lesions of the vascular wall with a media totally replaced by amyloid substance may be observed. CLINICAL EXPRESSION: Lobular hemorrhage, often with recurrent episodes is the most frequent manifestation of cerebral amyloid angiopathy. Cerebral infarcts or leukoencephalopathy may also be observed. An association with cerebral angiitis has been reported in a few cases. SPORADIC OR FAMILIAL DISEASE: Several types can be distinguished depending on the sporadic or familiar nature of the disease pattern as well as the chemical make-up of the protein deposit. In sporadic cerebral amyloid angiopathy the deposit is composed of protein A beta, and in familial cases, of protein A beta, cystatin C, gelsosine or transthyretin. Mutation of the genes coding for amyloid substance constituents have been identified in diverse forms of familial cerebral amyloid angiopathy.

Leys D, Erkinjuntti T, Desmond DW, Schmidt R, Englund E, Pasquier F, Parnetti L, Ghika J, Kalaria RN, Chabriat H, Scheltens P, Bogousslavsky J. · University of Lille, France. · Alzheimer Dis Assoc Disord. · Pubmed #10609680 No free full text.

Abstract: Although vascular dementia (VaD) is the second most frequent cause of dementia after Alzheimer disease (AD), the concept remains controversial in terms of delineation. The objective of this review is to investigate, from available literature, the role of cerebral infarcts in the pathogenesis of VaD and to identify areas of interest that need further evaluation and research. The incidence of new onset dementia is increased after stroke. Stroke subtypes, total volume of cerebral infarction and functional tissue loss, and location of the lesions are probably the major determinants of VaD. Any cause of stroke can lead to VaD. In some circumstances the causal relation between stroke and dementia is clear: (1) in young patients who are unlikely to have associated Alzheimer pathology; (2) when the cognitive functioning was normal before stroke, impaired immediately after, and does not worsen over time; (3) when the lesions are located in strategic areas; and (4) when a well-defined vasculopathy known to cause dementia is proven. However, several issues remain unsolved in VaD: lack of specificity of the diagnostic criteria; influence of white matter changes and associated Alzheimer pathology; influence of preexisting cognitive status; possibility of having VaD without stroke and the clinical relevance of silent infarcts to VaD; and best therapeutic strategy to be used to prevent VaD and to prevent stroke in patients with VaD. These questions form the basis for proposals for future research.

Pasquier F, Hénon H, Leys D. · Centre de la Mémoire, Centre Hospitalier et Universitaire de Lille. · Rev Neurol (Paris). · Pubmed #10528361 No free full text.

Abstract: Stroke significantly increases the risk of dementia in subjects aged 55 years or more. Twenty to 25 p. 100 of patients are demented 5 years after a stroke. Age and supratentorial location of the vascular lesion are risk factors for post-stroke dementia. Volume, left side of the lesion, large middle cerebral artery infarction, lesions of the frontal lobe, second stroke, diabetes, aphasia, clinical features expressing the severity of the stroke event in the acute phase, mitral valve prolapse, atrial fibrillation, depression, concomitant hypoxic/ischemic disorders, and white matter changes have also been found as predictors of dementia. There are many different mechanisms of vascular pathology that may lead to dementia: ischemic or hemorrhagic lesions, large vessel disease including multi-infarct and strategic single infarct, small-vessel disease including lacunes and white matter changes, hypoperfusion.... Post-stroke dementia may not be due only to vascular lesion. Some post-stroke dementias have a progressive onset and course. The cognitive decline may pre-exist to the stroke, even when a dementia is not diagnosed. This suggests a degenerative process. Alzheimer's disease is frequent in ages when the majority of strokes occur. Alzheimer's and vascular diseases share common risk factors such as age, APOE4, hypertension, and smoking. Patients with low MMS scores and AD patients are at risk for stroke. Moreover, white matter changes are associated with stroke and Alzheimer's disease and may contribute to the cognitive decline. Many post-stroke dementias could be multifactorial. Even when vascular lesions and degenerative changes (mainly Alzheimer changes) are not severe enough, no their own, to be the cause of dementia, their summation may reduce the preclinical stage of the degenerative process.

Leys D, Pasquier F. · Service de neurologie et pathologie neurovasculaire, Hôpital Roger Salengro. · Rev Neurol (Paris). · Pubmed #10528360 No free full text.

Abstract: Arterial hypertension is the leading risk factor for all stroke subtypes. However, its relationship with cognitive decline and dementia is more complex than a simple causal relationship. Cognitive functions are worse in patients with arterial hypertension, especially when the level of education is lower, age higher and arterial hypertension more severe. Arterial hypertension is an independent factor of cognitive decline. It also leads to white matter changes which contribute to the cognitive decline. Longitudinal studies have shown that a higher blood pressure at the age of 70 years is associated with an increased risk of dementia (vascular or Alzheimer) 10 to 15 years later, but blood pressure spontaneously decreases as dementia occurs. Treatments of arterial hypertension decrease the incidence of stroke, but clinical trials are still necessary to determine if they also decrease the incidence of dementia. Preliminary results obtained in elderly subjects with systolic arterial hypertension, support this hypothesis.

Bombois S, Debette S, Bruandet A, Delbeuck X, Delmaire C, Leys D, Pasquier F. · Department of Neurology, EA 2691, Memory Center, University Hospital 59037 Lille, France. · Stroke. · Pubmed #18436882 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Patients with mild cognitive impairment (MCI) have an increased risk of dementia. The identification of predictors of conversion to dementia is therefore important. The aim of our study was to test the hypothesis that subcortical hyperintensities (SH) are associated with an increased rate of conversion to dementia in MCI patients. METHODS: This was an observational study on consecutive MCI patients attending a memory clinic. We assessed SH on a baseline MRI scan, using a semiquantitative rating scale. A multivariable Cox regression model was used to test the association of SH with conversion to dementia. RESULTS: We included 170 MCI patients. The median duration of follow-up was 3.8 years. During this period, 67 patients (39.4%, 95% CI: 32.1 to 46.8%) developed dementia: Alzheimer disease (AD) in 29 patients, dementia with Lewy bodies in 19, mixed dementia in 8, vascular dementia in 7, fronto-temporal dementia in 2, and primary progressive aphasia in 2. SH were not associated with the risk to develop dementia as a whole, including AD. However, the risk to develop vascular or mixed dementia increased significantly with increasing amounts of SH at baseline (HR=1.14 [95% CI: 1.06 to 1.24]), especially periventricular hyperintensities (HR=2.71 [95% CI: 1.60 to 4.58]), independently of medial temporal lobe atrophy, age, gender, vascular risk factors, education, and cognitive functions at baseline. CONCLUSIONS: The risk of vascular or mixed dementia, but not of other types of dementia, was significantly increased in MCI patients with a large amount of subcortical hyperintensities at baseline.

Cordonnier C, van der Flier WM, Sluimer JD, Leys D, Barkhof F, Scheltens P. · Department of Neurology, Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands. · Neurology. · Pubmed #16682667 No free full text.

Abstract: OBJECTIVE: To determine prevalence and severity of microbleeds (MBs) in a large cohort of patients attending a memory clinic. METHODS: The authors consecutively included patients attending their memory clinic between January 2002 and April 2005. They analyzed prevalence and number of MBs according to demographic, diagnostic, and MRI data. RESULTS: The authors included 772 patients (53% men, age 66 +/- 11). One hundred twenty-seven patients (17%) exhibited at least one MB. The prevalence differed according to diagnostic groups (p < 0.0001): Sixty-five percent of patients with vascular dementia exhibited MBs vs 18% of Alzheimer disease patients, 20% of mild cognitive impairment patients, and 10% of patients with subjective complaints. The presence of MBs was associated with age, white matter hyperintensities, lacunar infarcts, and infarcts. CONCLUSION: The prevalence of microbleeds (MBs) in a large cohort of patients attending a memory clinic is higher than previously described in community samples and lower than reported in stroke patients. This finding of a relatively high proportion of MBs in Alzheimer disease and mild cognitive impairment provides further evidence for the involvement of vascular factors in neurodegenerative diseases such as Alzheimer disease.

Cordoliani-Mackowiak MA, Hénon H, Pruvo JP, Pasquier F, Leys D. · Department of Neurology, Stroke Unit, University of Lille, Lille, France. · Arch Neurol. · Pubmed #12707073 links to  free full text

Abstract: BACKGROUND: The prevalence of dementia is increased after stroke. Medial temporal lobe atrophy (MTLA) is associated with Alzheimer disease, and with prestroke dementia in patients who have had a stroke. OBJECTIVE: To determine the influence of MTLA on the long-term risk of dementia after stroke, after excluding the patients who had prestroke dementia. METHODS: The study was conducted in 144 consecutive patients who had a stroke, who were aged 40 years or older (66 women and 78 men; median age, 72 years), and who had an Informant Questionnaire on Cognitive Decline in the Elderly score lower than 104. On admission to the hospital all patients underwent a noncontrast computed tomographic scan including temporal lobe-positioned slices. A cut-off of 11.5 mm was used to differentiate patients with MTLA from those without MTLA. Patients were followed up with clinical and cognitive assessments over a 3-year period. RESULTS: Three years after stroke, 34 patients (23.6%) had developed new-onset dementia. The cumulative proportion of survivors without dementia was 57.6% in patients with MTLA and 80.8% in patients without MTLA (P =.02). The unadjusted relative risk of poststroke dementia associated with MTLA was 2.3 (95% confidence interval, 1.1-4.7). However, using the Cox proportional hazards model, MTLA did not seem to be an independent predictor of poststroke dementia. Independent predictors of poststroke dementia were increasing age, diabetes mellitus, severity of the clinical deficit at admission, and severity of leukoaraiosis on computed tomography. CONCLUSIONS: Patients who had a stroke and MTLA more frequently develop dementia than patients without MTLA, but our study does not suggest that MTLA independently contributes to dementia. A longer follow-up may be necessary to reevaluate the influence of MTLA.

Pasquier F, Hénon H, Leys D. · Department of Neurology, EA 2691 MENRT, University Hospital of Lille, France. · Ann N Y Acad Sci. · Pubmed #10818539 No free full text.

Abstract: White matter changes are often associated with stroke, risk factors for stroke, and dementia. From a theoretical point of view, they may be associated with an increased risk of pre- or poststroke dementia because (i) they are linked with subtle cognitive decline, which may add to the consequences of the stroke lesions and of associated Alzheimer pathology; and (ii) they indicate an increased risk of stroke recurrence. The aim of this study was to evaluate the contribution of white matter changes to pre- and poststroke dementia. The relationship between preexisting dementia and white matter changes was evaluated in the Lille stroke-dementia cohort. We assessed the cognitive functioning prior to stroke in 202 consecutive patients with ischemic or hemorrhagic stroke, by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We classified in the dementia group patients with IQCODE scores of 104 or more. White matter changes were rated on CT with the Blennow's rating scale. Thirty-three of 202 patients were demented before stroke (16.3%; 95% confidence interval: 11.2-21.4); the logistic regression analysis found that female sex, family dementia, white matter changes, and cerebral atrophy were independently associated with prestroke dementia. White matter changes were also associated with an increased risk of poststroke dementia, 2 years after stroke onset. Thus, white matter changes contribute to dementia occurring in stroke patients.

Leys D, Pasquier F. · No affiliation provided · Lancet. · Pubmed #9923898 No free full text.

This publication has no abstract.