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Authors' reply

Michaël Schwarzinger, Carol Dufouil, Jürgen Rehm
2018 Lancet Public Health  
doi:10.1016/s2468-2667(18)30074-4 pmid:29731157 fatcat:k2477aaoyvbklc2vcahmz4bl5e

Beyond mild cognitive impairment: vascular cognitive impairment, no dementia (VCIND)

Blossom CM Stephan, Fiona E Matthews, Kay-Tee Khaw, Carole Dufouil, Carol Brayne
2009 Alzheimer's Research & Therapy  
Identifying the causes of dementia is important in the search for effective preventative and treatment strategies. The concept of mild cognitive impairment (MCI), as prodromal dementia, has been useful but remains controversial since in population-based studies it appears to be a limited predictor of progression to dementia. Recognising the relative contribution of neurodegenerative and vascular causes, as well as their interrelationship, may enhance predictive accuracy. The concept of vascular
more » ... cognitive impairment (VCI) has been introduced to describe the spectrum of cognitive change related to vascular causes from early cognitive decline to dementia. A recent review of this concept highlighted the need for diagnostic criteria that encompass the full range of the VCI construct. However, very little is known regarding the mildest stage of VCI, generally termed 'vascular cognitive impairment, no dementia' (VCIND). Whether mild cognitive change in the context of neurodegenerative pathologies is distinct from that in the context of cerebrovascular diseases is not known. This is key to the definition of VCIND and whether it is possible to identify this state. Distinguishing between vascular (that is, VCIND) and non-vascular (that is, MCI) cognitive disorders and determining how well each might predict dementia may not be possible due to the overlap in pathologies observed in the older population. Here, we review the concept of VCIND in an effort to identify recent developments and areas of controversy in nosology and the application of VCIND for screening individuals at increased risk of dementia secondary to vascular disease and its risk factors. Age-related changes in the vascular system Ageing in the developed world is associated with changes in the vascular system which result in atherogenesis, increased pulse pressure and increased risk of developing vascular disease as a consequence of a direct effect on the vascular system (for example, arterial hypertension and vasculitis) or AD = Alzheimer disease; A-MCI = anmestic subtype of mild cognitive impairment; MCI = mild cognitive impairment; VaD = vascular dementia; VCI = vascular cognitive impairment; VCIND = vascular cognitive impairment, no dementia.
doi:10.1186/alzrt4 pmid:19674437 pmcid:PMC2719105 fatcat:ysx76s7xpjg2rpbj6leq7ev5ee

Interaction between genes and environment in neurodegenerative diseases

Alexis Elbaz, Carole Dufouil, Annick Alpérovitch
2007 Comptes rendus. Biologies  
Alzheimer's disease (AD) and Parkinson's disease (PD) are highly prevalent disorders that account for a large part of the global burden of neurodegenerative diseases. Most AD and PD cases occur sporadically and it is generally agreed that they could arise through interactions among genetic and environmental factors. Candidate genes involved in the metabolism of xenobiotics, neurodegeneration and functioning of dopaminergic neurons were found to be associated with PD. Some of these genes
more » ... with environmental factors that could modify PD risk. Thus, we found that the inverse association between smoking and the risk of PD depended on a polymorphism of the iNOS (inducible NO synthase) gene. We also found that the cytochrome P450 2D6 gene could have a modifying effect on the risk of PD among persons exposed to pesticides. Both interactions have biological plausibility supported by laboratory studies and could contribute to better understand the aetiology of PD. A single susceptibility gene has been identified in sporadic AD. The ε4 allele of epsilon polymorphism of the apolipoprotein E gene (APOE) is strongly associated with AD, the risk of AD being multiplied by 5 in persons carrying two ε4 alleles. The mechanism of the association between APOE and AD is poorly understood. A few interactions between the epsilon polymorphism and possible risk factors for AD have been described. However, these interactions had no biological plausibility and were likely due to chance. To cite this article: A. Elbaz et al., C. R. Biologies 330 (2007). (A. Alpérovitch). disease burden for developed regions [1, 2] . The GBD researchers have also weighted the severity of disability for a series of health conditions. Out of the ten disorders within the three highest disability classes, eight are neurological problems. According to the WHO, neurodegenerative diseases will become the world's second leading cause of death by the middle of the century, overtaking cancer [2] . Although such rough rankings and predictions are questionable, they confirm that neurodegenerative diseases are an increasing public con-1631-0691/$ -see front matter
doi:10.1016/j.crvi.2007.02.018 pmid:17502288 fatcat:tnhsl3moqrfjlnxhd6ugins6qe


Blossom Christa Maree Stephan, Eugene Tang, Stephanie L. Harrison, Mark Gordon, Pieter Jelle Visser, Gerald Novak, Louise A. Robinson, Carole Dufouil, Fiona E. Matthews, Carol Brayne
2014 Alzheimer's & Dementia  
Numerous dementia risk prediction models have been developed in the past decade. However, methodological limitations of the analytical tools used may hamper their ability to generate reliable dementia risk scores. We aim to review the used methodologies. Methods: We systematically reviewed the literature from March 2014 to September 2018 for publications presenting a dementia risk prediction model. We critically discuss the analytical techniques used in the literature. Results: In total 137
more » ... ications were included in the qualitative synthesis. Three techniques were identified as the most commonly used methodologies: machine learning, logistic regression, and Cox regression. Discussion: We identified three major methodological weaknesses: (1) over-reliance on one data source, (2) poor verification of statistical assumptions of Cox and logistic regression, and (3) lack of validation. The use of larger and more diverse data sets is recommended. Assumptions should be tested thoroughly, and actions should be taken if deviations are detected.
doi:10.1016/j.jalz.2014.05.978 fatcat:agdlobhkxbh2jkl7r36h2shoqe

Abaisser la pression artérielle permet de limiter la microangiopathie cérébrale

Christophe Tzourio, Carole Dufouil, Nathalie Tzourio-Mazoyer
2006 M S.Médecine Sciences  
Dufouil, Nathalie Tzourio-Mazoyer NOUVELLE séquences ont été réalisés ces dernières années.  ...  l'utilisation de l'outil épidémiologique que des progrès substantiels sur leurs mécanismes et leurs con- Abaisser lapressionartérielle permetdelimiter lamicroangiopathiecérébrale Christophe Tzourio, Carole  ... 
doi:10.1051/medsci/2006222104 pmid:16457741 fatcat:iibbs3kj3nf6bkjwxa3kzgkbuq

Depressive symptoms and cognitive decline in elderly people

Sabrina Paterniti, Marie-Hélène Verdier-Taillefer, Carole Dufouil, Annick Alpérovitch
2002 British Journal of Psychiatry  
Some studies did not report any significant association did not report any significant association (Dufouil (Dufouil et al et al, 1996; Palsson , 1996; Palsson et al et al, 1999) . , 1999).  ...  Dufouil, C., Fuhrer, R., Dartigues, J. F., Dufouil, C., Fuhrer, R., Dartigues, J.  ... 
doi:10.1192/bjp.181.5.406 pmid:12411266 fatcat:mdpdkax7wrhvjm76mxkqqape2q

Migraine and cognitive decline in the population-based EVA study

Pamela M Rist, Carole Dufouil, M Maria Glymour, Christophe Tzourio, Tobias Kurth
2011 Cephalalgia  
Background-Previous studies on migraine and cognition have shown mixed results. However, many could not assess the relationship between migraine and change in cognitive function or only used a limited number of cognitive tests. Methods-Prospective cohort study among 1170 participants of the Epidemiology of Vascular Aging Study who provided information about migraine status and completed cognitive testing. Participants were classified as having no severe headache, non-migraine headache and
more » ... ne. Cognitive functioning was measured at up to four time points using nine different cognitive 3. Waldie KE, Hausmann M, Milne BJ, Poulton R. Migraine and cognitive function: a life-course study. Neurology. 2002;59:904-8. ( 4. Pearson AJ, Chronicle EP, Maylor EA, Bruce LA. Cognitive function is not impaired in people with a long history of migraine: a blinded study. Cephalalgia. 2006;26:74-80. ( 5. Scher AI, Gudmundsson LS, Sigurdsson S, Ghambaryan A, Aspelund T, Eiriksdottir G, et al. Migraine headache in middle age and late-life brain infarcts.
doi:10.1177/0333102411417466 pmid:21816772 pmcid:PMC3175294 fatcat:i2jhj47pdrfnpk7tnsjlvsqw7u

Current Developments in Dementia Risk Prediction Modelling: An Updated Systematic Review

Eugene Y. H. Tang, Stephanie L. Harrison, Linda Errington, Mark F. Gordon, Pieter Jelle Visser, Gerald Novak, Carole Dufouil, Carol Brayne, Louise Robinson, Lenore J. Launer, Blossom C. M. Stephan, Gianluigi Forloni
2015 PLoS ONE  
Accurate identification of individuals at high risk of dementia influences clinical care, inclusion criteria for clinical trials and development of preventative strategies. Numerous models have been developed for predicting dementia. To evaluate these models we undertook a systematic review in 2010 and updated this in 2014 due to the increase in research published in this area. Here we include a critique of the variables selected for inclusion and an assessment of model prognostic performance.
more » ... ethods Our previous systematic review was updated with a search from January 2009 to March 2014 in electronic databases (MEDLINE, Embase, Scopus, Web of Science). Articles examining risk of dementia in non-demented individuals and including measures of sensitivity, specificity or the area under the curve (AUC) or c-statistic were included. Findings In total, 1,234 articles were identified from the search; 21 articles met inclusion criteria. New developments in dementia risk prediction include the testing of non-APOE genes, use of non-traditional dementia risk factors, incorporation of diet, physical function and ethnicity, and model development in specific subgroups of the population including individuals with PLOS ONE | diabetes and those with different educational levels. Four models have been externally validated. Three studies considered time or cost implications of computing the model. Interpretation There is no one model that is recommended for dementia risk prediction in populationbased settings. Further, it is unlikely that one model will fit all. Consideration of the optimal features of new models should focus on methodology (setting/sample, model development and testing in a replication cohort) and the acceptability and cost of attaining the risk variables included in the prediction score. Further work is required to validate existing models or develop new ones in different populations as well as determine the ethical implications of dementia risk prediction, before applying the particular models in population or clinical settings.
doi:10.1371/journal.pone.0136181 pmid:26334524 pmcid:PMC4559315 fatcat:gygjqfsswrgf5gihs6rmynxerm

Predictors of COVID-19 vaccine acceptance across time and countries [article]

John R. Kerr, Claudia R. Schneider, Gabriel Recchia, Sarah Dryhurst, Ullrika Sahlin, Carole Dufouil, Pierre Arwidson, Alexandra L.J. Freeman, Sander van der Linden
2020 medRxiv   pre-print
Understanding the drivers of vaccine acceptance is crucial to the success of COVID-19 mass vaccination campaigns. Across 25 national samples from 12 different countries we examined the psychological correlates of willingness to receive a COVID-19 vaccine (total N = 25,334), with a focus on risk perception and trust in a number of relevant actors, both in general and specifically regarding the COVID-19 pandemic. Male sex, trust in medical and scientific experts and worry about the virus emerge
more » ... the most consistent predictors of reported vaccine acceptance across countries. In a subset of samples we show that these effects are robust after controlling for attitudes towards vaccination in general. Our results indicate that the burden of trust largely rests on the shoulders of the scientific and medical community, with implications for how future COVID-19 vaccination information should be communicated to maximize uptake.
doi:10.1101/2020.12.09.20246439 fatcat:ssvw4yavjvfermvjiy2mtuo5ce

Hypertension and lower walking speed in the elderly: the Three-City study

Julien Dumurgier, Alexis Elbaz, Carole Dufouil, Béatrice Tavernier, Christophe Tzourio
2010 Journal of Hypertension  
The brain is one of the main targets of hypertension. However, little is known about the relation between hypertension and motor performances. We studied the association between hypertension and walking speed in a cohort of elderly people. Analyses are based on participants (65-85 years) from the Dijon (France) center of the Three-City study (n = 3604), followed every 2 years. Persistent hypertension was defined by the use of antihypertensive drugs at baseline or at first follow-up, or by high
more » ... lood pressure (> or =140/90 mmHg) at baseline and first follow-up. Walking speed was measured over 6 m, at baseline and fourth follow-up (n = 1774) after a mean (SD) duration of 7.0 (0.5) years. Brain MRI was performed in 1590 participants. Generalized linear models were used to assess the relation between hypertension and baseline walking speed or walking speed change. At baseline, mean (SD) walking speed (m/s) was lower in hypertensive patients [1.51 (0.31)] than in nonhypertensive individuals [1.59 (0.30), P < 0.001]. During follow-up, hypertensive patients had a higher mean annual decline in walking speed [cm/s per year; 2.30 (3.4)] than nonhypertensive individuals [1.87 (3.3), P = 0.004]. The number of antihypertensive drugs was associated with lower walking speed at baseline and higher walking speed decline. Adjustment for MRI white matter abnormalities attenuated these relations. Persistent hypertension was associated with both lower walking speed and higher decline in walking speed in the elderly. These results may be partly explained by white matter abnormalities and support the hypothesis of a contribution of vascular risk factors to motor dysfunction.
doi:10.1097/hjh.0b013e328338bbec pmid:20404744 pmcid:PMC4851985 fatcat:gs52gctap5ar3dfqaq5iwa7aim

Gender Differences in the Association between Socioeconomic Status and Subclinical Atherosclerosis

Olivier Grimaud, Annabelle Lapostolle, Claudine Berr, Catherine Helmer, Carole Dufouil, Wahida Kihal, Annick Alpérovitch, Pierre Chauvin, Angelo Scuteri
2013 PLoS ONE  
Objectives: This study explored the pattern of associations between socioeconomic status (SES) and atherosclerosis progression (as indicated by carotid intima media thickness, CIMT) across gender. Design: Cross-sectional analysis of a sample of 5474 older persons (mean age 73 years) recruited between 1999 and 2001 in the 3C study (France). We fitted linear regression models including neighborhood SES, individual SES and cardiovascular risk factors. Results: CIMT was on average 24 mm higher in
more » ... n (95% CI: 17 to 31). Neighborhood SES was inversely associated with CIMT in women only (highest versus lowest tertiles: 212.2 mm, 95%CI 222 to 22.4). This association persisted when individual SES and risk factors were accounted for. High individual education was associated with lower CIMT in men (221.4 mm 95%CI 237.5 to 25.3) whereas high professional status was linked to lower CIMT among women (215.7 mm 95%CI: 229.2 to 22.2). Adjustment for cardiovascular risk factors resulted in a slightly more pronounced reduction of the individual SES-CIMT association observed in men than in women. Conclusion: In this sample, neighborhood and individual SES displayed different patterns of associations with subclinical atherosclerosis across gender. This suggests that the causal pathways leading to SES variations in atherosclerosis may differ among men and women.
doi:10.1371/journal.pone.0080195 pmid:24282522 pmcid:PMC3839909 fatcat:uve6oqwzpffa5ekgenrqy4dzoy

Inflammatory Proteins and the Severity of Dilated Virchow-Robin Spaces in the Elderly

Claudia L. Satizabal, Yi-Cheng Zhu, Carole Dufouil, Christophe Tzourio
2012 Journal of Alzheimer's Disease  
Exclusion criteria for scans were: 1) presence of an internal electrical/magnetic device; 2) history of neurosurgery or aneurysm; 3) presence of metal fragments in the eyes, brain, or spinal cord; and 4) claustrophobia. MRI acquisition was performed on a 1.5-Tesla Magnetom (Siemens; Erlangen, DE). A three-dimensional high-resolution T1-weighted brain volume was acquired using a three-dimensional inversion recovery fast spoiled-gradient echo sequence (repetition time = 97 ms; echo time = 4 ms;
more » ... version time = 600 ms; coronal acquisition). The axially reoriented three-dimensional volume matrix was 256 × 192 × 256 size with a 1.0 × 0.98 × 0.98 mm 3 voxel size, yielding 124 slices covering the whole brain. T2-and proton density-weighted brain volumes were acquired using a two-dimensional dual spin echo sequence with two echo times (repetition time = 4,400 ms; echo time 1 = 16 ms; echo time 2 = 98 ms). T2 and proton density acquisitions consisted of 35 axial slices 3.5 mm thick (0.5 mm spacing), . having a 256 × 256 matrix size, and a 0.98 × 0.98 mm 2 in-plane resolution. dVRS RATING In basal ganglia, the degree of severity was defined according the slice containing the greatest number of dVRS as 1st: <5 dVRS; 2nd: 5 to 10 dVRS; 3rd: >10 dVRS but still numerable; and 4th: innumerable dVRS resulting in a cribriform change in basal ganglia. In white matter, the degree of severity was defined as 1st: ≤10 dVRS in total white matter; 2nd: >10 dVRS in total white matter and <10 dVRS in the slice containing the greatest number of dVRS; 3rd: 10 to 20 dVRS in the slice containing the greatest number of dVRS; and 4th: >20 dVRS in the slice containing the greatest number of dVRS (see Supplementary Table 1 ). The intra-rater agreement was of κ = 0.77 for basal ganglia and κ = 0.75 for white matter.
doi:10.3233/jad-2012-120874 pmid:22976070 fatcat:v27xs6szqjacbczm77jl2swayi

Incidence of Dementia over Three Decades in the Framingham Heart Study

Claudia L. Satizabal, Alexa S. Beiser, Vincent Chouraki, Geneviève Chêne, Carole Dufouil, Sudha Seshadri
2016 New England Journal of Medicine  
BACKGROUND The prevalence of dementia is expected to soar as the average life expectancy increases, but recent estimates suggest that the age-specific incidence of dementia is declining in high-income countries. Temporal trends are best derived through continuous monitoring of a population over a long period with the use of consistent diagnostic criteria. We describe temporal trends in the incidence of dementia over three decades among participants in the Framingham Heart Study. METHODS
more » ... ants in the Framingham Heart Study have been under surveillance for incident dementia since 1975. In this analysis, which included 5205 persons 60 years of age or older, we used Cox proportional-hazards models adjusted for age and sex to determine the 5-year incidence of dementia during each of four epochs. We also explored the interactions between epoch and age, sex, apolipoprotein E ε4 status, and educational level, and we examined the effects of these interactions, as well as the effects of vascular risk factors and cardiovascular disease, on temporal trends. RESULTS The 5-year age-and sex-adjusted cumulative hazard rates for dementia were 3.6 per 100 persons during the first epoch (late 1970s and early 1980s), 2.8 per 100 persons during the second epoch (late 1980s and early 1990s), 2.2 per 100 persons during the third epoch (late 1990s and early 2000s), and 2.0 per 100 persons during the fourth epoch (late 2000s and early 2010s). Relative to the incidence during the first epoch, the incidence declined by 22%, 38%, and 44% during the second, third, and fourth epochs, respectively. This risk reduction was observed only among persons who had at least a high school diploma (hazard ratio, 0.77; 95% confidence interval, 0.67 to 0.88). The prevalence of most vascular risk factors (except obesity and diabetes) and the risk of dementia associated with stroke, atrial fibrillation, or heart failure have decreased over time, but none of these trends completely explain the decrease in the incidence of dementia. CONCLUSIONS Among participants in the Framingham Heart Study, the incidence of dementia has declined over the course of three decades. The factors contributing to this
doi:10.1056/nejmoa1504327 pmid:26863354 pmcid:PMC4943081 fatcat:x2ykcht4lbbh7k5mp4aajwqpjy

Structural brain lesions and restless legs syndrome: a cross-sectional population-based study

Pamela M Rist, Christophe Tzourio, Alexis Elbaz, Aïcha Soumaré, Carole Dufouil, Bernard Mazoyer, Tobias Kurth
2014 BMJ Open  
Objective: To evaluate the association between white matter lesion (WML) volume, silent infarcts and restless legs syndrome (RLS) in a population-based study of elderly individuals. Primary outcome measure: Prevalence of RLS. Results: WML volume was measured using an automated tissue segmentation method. Logistic regression was used to evaluate adjusted associations between tertiles of WML volume and RLS and between silent infarcts and RLS. 218 individuals (21.1%) were determined to have RLS.
more » ... mpared with those in the first tertile of WML volume, individuals in the second tertile (OR=1.09; 95% CI 0.75 to 1.60) or third tertile (OR=1.17; 95% CI 0.79 to 1.74) did not have an increased prevalence of RLS. We also did not observe associations between the volume of deep or periventricular WML and RLS; nor did we observe an association between silent brain infarcts and RLS (OR=0.74; 95% CI 0.40 to 1.39). These findings were not modified by age or gender. Conclusions: Higher volume of WML and the presence of silent infarcts were not associated with an increased prevalence of RLS in this population-based cohort of elderly individuals.
doi:10.1136/bmjopen-2014-005938 pmid:25421338 pmcid:PMC4244423 fatcat:y3vev37mufhsnf6ydpcor6yhem
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