The seeds of divergence: the economy of French North America, 1688 to 1760

Generally, Canada has been ignored in the literature on the colonial origins of divergence with most of the attention going to the United States. Late nineteenth century estimates of income per capita show that Canada was relatively poorer than the United States and that within Canada, the French and Catholic population of Quebec was considerably poorer. Was this gap long standing? Some evidence has been advanced for earlier periods, but it is quite limited and not well-suited for comparison with other societies. This thesis aims to contribute both to Canadian economic history and to comparative work on inequality across nations during the early modern period. With the use of novel prices and wages from Quebec—which was then the largest settlement in Canada and under French rule—a price index, a series of real wages and a measurement of Gross Domestic Product (GDP) are constructed. They are used to shed light both on the course of economic development until the French were defeated by the British in 1760 and on standards of living in that colony relative to the mother country, France, as well as the American colonies. The work is divided into three components. The first component relates to the construction of a price index. The absence of such an index has been a thorn in the side of Canadian historians as it has limited the ability of historians to obtain real values of wages, output and living standards. This index shows that prices did not follow any trend and remained at a stable level. However, there were episodes of wide swings—mostly due to wars and the monetary experiment of playing card money. The creation of this index lays the foundation of the next component. The second component constructs a standardized real wage series in the form of welfare ratios (a consumption basket divided by nominal wage rate multiplied by length of work year) to compare Canada with France, England and Colonial America. Two measures are derived. The first relies on a “bare bones” definition of consumption with a large share of land-intensive goods. This measure indicates that Canada was poorer than England and Colonial America and not appreciably richer than France. However, this measure overestimates the relative position of Canada to the Old World because of the strong presence of land-intensive goods. A second measure is created using a “respectable” definition of consumption in which the basket includes a larger share of manufactured goods and capital-intensive goods. This second basket better reflects differences in living standards since the abundance of land in Canada (and Colonial America) made it easy to achieve bare subsistence, but the scarcity of capital and skilled labor made the consumption of luxuries and manufactured goods (clothing, lighting, imported goods) highly expensive. With this measure, the advantage of New France over France evaporates and turns slightly negative. In comparison with Britain and Colonial America, the gap widens appreciably. This element is the most important for future research. By showing a reversal because of a shift to a different type of basket, it shows that Old World and New World comparisons are very sensitive to how we measure the cost of living. Furthermore, there are no sustained improvements in living standards over the period regardless of the measure used. Gaps in living standards observed later in the nineteenth century existed as far back as the seventeenth century. In a wider American perspective that includes the Spanish colonies, Canada fares better. The third component computes a new series for Gross Domestic Product (GDP). This is to avoid problems associated with using real wages in the form of welfare ratios which assume a constant labor supply. This assumption is hard to defend in the case of Colonial Canada as there were many signs of increasing industriousness during the eighteenth and nineteenth centuries. The GDP series suggest no long-run trend in living standards (from 1688 to circa 1765). The long peace era of 1713 to 1740 was marked by modest economic growth which offset a steady decline that had started in 1688, but by 1760 (as a result of constant warfare) living standards had sunk below their 1688 levels. These developments are accompanied by observations that suggest that other indicators of living standard declined. The flat-lining of incomes is accompanied by substantial increases in the amount of time worked, rising mortality and rising infant mortality. In addition, comparisons of incomes with the American colonies confirm the results obtained with wages— Canada was considerably poorer. At the end, a long conclusion is provides an exploratory discussion of why Canada would have diverged early on. In structural terms, it is argued that the French colony was plagued by the problem of a small population which prohibited the existence of scale effects. In combination with the fact that it was dispersed throughout the territory, the small population of New France limited the scope for specialization and economies of scale. However, this problem was in part created, and in part aggravated, by institutional factors like seigneurial tenure. The colonial origins of French America’s divergence from the rest of North America are thus partly institutional

Analyse de la morphologie des sillons corticaux et de l'activation microgliale dans la maladie d'Alzheimer : étude couplée en IRM, TEP-PiB et TEP-DPA

Alzheimer's disease (AD) is the leading cause of degenerative dementia. It is defined by the abnormal accumulation of tau and myloid proteins, constituting amyloid plaques. While the neuro-pathological involvement of AD is stereotyped in patients, its clinical expression and prognosis are heterogeneous. In this work, we analyzed two factors modulating the expression of the disease: age and microglial activation, which we studied in a population of AD patients (in the early and severe stages) and controls, defined on the basis of clinical-biological diagnostic criteria. We first analyzed the effect of age on the modification of the morphology of the cortical sulci during AD. We measured cortical sulcus opening and hippocampal volume on brain MRI of young AD subjects (65 years) and age-matched control subjects. Second, we studied microglial activation by quantifying [18F]-DPA-14 ligand binding using positron emission tomography (PET) in a population of AD subjects and controls followed clinically for two years. Finally, we measured and compared the evolution of microglial activation over time between AD subjects and controls, who benefited from a second PET scan. Our hypotheses were (1) that the study of cortical sulcus morphology was more efficient than the measurement of hippocampal volume to distinguish young forms of AD from elderly forms, (2) that compared to controls, microglial activation was more important in AD subjects and that it influenced the clinical progression of the disease, and (3) that there were different evolutionary profiles of microglial activation. Our results show (1) that the measurement of cortical sulcus opening is a better diagnostic marker than the measurement of hippocampal volume in the young AD group, from the early stage of the disease. Conversely, it leads to an overdiagnosis risk in the patient over 65 years of age, where the effect of age merges with that of the disease; (2) microglial activity is increased early in AD and is associated with cognitive and functional stability in AD. Finally, (3) that there are different profiles of microglial activation over time, with distinct repercussions on the progression of AD. All in all, this work confirms the heterogeneity of AD. The study of the effects of age and microglial activation in a population with AD reveals subtypes of patients with distinct expression and evolutionary trajectories; younger subjects present a more extensive cortical expression of the disease and subjects with low microglial activation have a more severe functional and cognitive deterioration. These variability factors open up avenues for clinical and therapeutic research. They could be taken into account in future therapeutic protocols.La maladie d’Alzheimer (MA) est la première cause de démence dégénérative. Elle est ‏définie par l’accumulation anormale des protéines Tau et myloïdes, constituant des plaques‏ amyloïdes. Alors que l’atteinte neuro-pathologique de la MA est stéréotypée chez les malades, son ‏expression clinique et son pronostic sont hétérogènes. Les facteurs modulant l’expression de la ‏maladie sont actuellement peu connus.‏ Dans ce travail, nous avons analysé deux facteurs modulateurs de l’expression de la ‏maladie : l’âge et l’activation microgliale que nous avons étudié au sein d’une population de sujets‏ atteints de la MA (aux stades débutant et sévère) et de témoins, définis sur des critères‏ diagnostiques clinico-biologiques. ‏Nous avons tout d’abord analysé l’effet de l’âge sur la modification de la morphologie des ‏sillons corticaux au cours de la MA. Nous avons mesuré l’ouverture des sillons corticaux ainsi que ‏le volume hippocampique sur l’IRM cérébrale de sujets MA jeunes (65 ans) ainsi que chez des sujets témoins appariés à l’âge. Dans un second temps, nous étudié ‏l’activation microgliale en quantifiant la fixation du ligand [18F]-DPA-14, grâce à la tomographie ‏par émission de positrons (TEP) au sein d’une population de sujets MA et de témoins suivis‏ cliniquement pendant deux ans. Finalement, nous avons mesuré et comparé l’évolution de‏ l’activation microgliale au cours du temps entre des sujets MA et des témoins, qui ont bénéficié de ‏la réalisation d’un second examen TEP. ‏Nos hypothèses étaient (1) que l’étude de la morphologie des sillons corticaux était plus ‏performante que la mesure du volume hippocamique pour distinguer les formes jeunes de MA des‏ formes du sujet âgé, (2) qu’en comparaison aux témoins, l’activation microgliale était plus‏ importante chez les sujets MA et qu’elle influait sur la progression clinique de la maladie, et (3)‏ qu’il existait différents profils évolutifs d’activation microgliale.‏ Nos résultats montrent (1) que la mesure de l’ouverture des sillons corticaux est un meilleur ‏marqueur diagnostique que la mesure du volume hippocampique dans le groupe de sujets MA jeune,‏ dès le stade débutant de la maladie. A l’inverse, elle entraîne un risque de diagnostic par excès chez ‏le patient de plus de 65 ans, où l’effet de l’âge se confond avec celui de la maladie ; (2) l'activité‏ microgliale est augmentée précocement au cours de la MA et est associée à une stabilité cognitive et fonctionnelle de la MA. Finalement, (3) qu’il existe différents profils d’activation microgliale‏ au cours du temps, avec des retentissements distincts sur la progression de la MA. Au total, ces travaux confirment l'hétérogéneité de la maladie d'Alzheimer. L'étude des ‏effets de l'âge et de l'activation microgliale au sein d'une population atteinte d'une MA met en‏ évidence des sous-types de malades avec une expression et des trajectoires évolutives distinctes ; ‏les sujets jeunes présentent une expression corticale de la maladie plus étendue et les sujets avec‏ une faible activation de la microglie ont une dégradation fonctionnelle et cognitive plus sévère. ‏Ces facteurs de variabilité ouvrent des pistes de recherche clinique mais aussi‏ thérapeutiques. Ils pourraient être pris en compte dans les protocoles thérapeutiques ultérieurs

Analyse de la morphologie des sillons corticaux et de l'activation microgliale dans la maladie d'Alzheimer : étude couplée en IRM, TEP-PiB et TEP-DPA

La maladie d’Alzheimer (MA) est la première cause de démence dégénérative. Elle est ‏définie par l’accumulation anormale des protéines Tau et myloïdes, constituant des plaques‏ amyloïdes. Alors que l’atteinte neuro-pathologique de la MA est stéréotypée chez les malades, son ‏expression clinique et son pronostic sont hétérogènes. Les facteurs modulant l’expression de la ‏maladie sont actuellement peu connus.‏ Dans ce travail, nous avons analysé deux facteurs modulateurs de l’expression de la ‏maladie : l’âge et l’activation microgliale que nous avons étudié au sein d’une population de sujets‏ atteints de la MA (aux stades débutant et sévère) et de témoins, définis sur des critères‏ diagnostiques clinico-biologiques.‏Nous avons tout d’abord analysé l’effet de l’âge sur la modification de la morphologie des ‏sillons corticaux au cours de la MA. Nous avons mesuré l’ouverture des sillons corticaux ainsi que ‏le volume hippocampique sur l’IRM cérébrale de sujets MA jeunes (65 ans) ainsi que chez des sujets témoins appariés à l’âge. Dans un second temps, nous étudié ‏l’activation microgliale en quantifiant la fixation du ligand [18F]-DPA-14, grâce à la tomographie ‏par émission de positrons (TEP) au sein d’une population de sujets MA et de témoins suivis‏ cliniquement pendant deux ans. Finalement, nous avons mesuré et comparé l’évolution de‏ l’activation microgliale au cours du temps entre des sujets MA et des témoins, qui ont bénéficié de ‏la réalisation d’un second examen TEP. ‏Nos hypothèses étaient (1) que l’étude de la morphologie des sillons corticaux était plus ‏performante que la mesure du volume hippocamique pour distinguer les formes jeunes de MA des‏ formes du sujet âgé, (2) qu’en comparaison aux témoins, l’activation microgliale était plus‏ importante chez les sujets MA et qu’elle influait sur la progression clinique de la maladie, et (3)‏qu’il existait différents profils évolutifs d’activation microgliale.‏Nos résultats montrent (1) que la mesure de l’ouverture des sillons corticaux est un meilleur ‏marqueur diagnostique que la mesure du volume hippocampique dans le groupe de sujets MA jeune,‏ dès le stade débutant de la maladie. A l’inverse, elle entraîne un risque de diagnostic par excès chez ‏le patient de plus de 65 ans, où l’effet de l’âge se confond avec celui de la maladie ; (2) l'activité‏ microgliale est augmentée précocement au cours de la MA et est associée à une stabilité cognitive et fonctionnelle de la MA. Finalement, (3) qu’il existe différents profils d’activation microgliale‏ au cours du temps, avec des retentissements distincts sur la progression de la MA. ‏ Au total, ces travaux confirment l'hétérogéneité de la maladie d'Alzheimer. L'étude des‏effets de l'âge et de l'activation microgliale au sein d'une population atteinte d'une MA met en‏ évidence des sous-types de malades avec une expression et des trajectoires évolutives distinctes ; ‏les sujets jeunes présentent une expression corticale de la maladie plus étendue et les sujets avec‏ une faible activation de la microglie ont une dégradation fonctionnelle et cognitive plus sévère. ‏Ces facteurs de variabilité ouvrent des pistes de recherche clinique mais aussi‏ thérapeutiques. Ils pourraient être pris en compte dans les protocoles thérapeutiques ultérieurs. ‏No abstrac

L'imagerie par résonance magnétique pour le diagnostic précoce de la maladie d'Alzheimer

National audienceA major challenge for neuroimaging is to contribute to the early diagnosis of Alzheimer's disease (AD). In particular, magnetic resonance imaging (MRI) allows detecting different types of structural and functional abnormalities at an early stage of the disease. Anatomical MRI is the most widely used technique and provides local and global measures of atrophy. The recent diagnostic criteria of "mild cognitive impairment due to AD" include hippocampal atrophy, which is considered a marker of neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in the hippocampus and throughout the whole brain. Recent modalities such as diffusion-tensor imaging and resting-state functional MRI provide additional measures that could contribute to the early diagnosis but require further validation.Un des enjeux majeurs de la neuroimagerie est de contribuer au diagnostic précoce de la maladie d’Alzheimer. L’imagerie par résonance magnétique (IRM) permet de détecter différents types d’altérations structurelles et fonctionnelles dès les premiers stades de la maladie. L’IRM anatomique est la technique la plus répandue et fournit des mesures d’atrophie cérébrale locales ou régionales. Les nouveaux critères de diagnostic de la maladie d’Alzheimer au stade des troubles cognitifs légers incluent l’atrophie hippocampique, qui est alors considéré comme un marqueur d’atteinte neuronale. Les techniques avancées d’analyse d’images génèrent des mesures automatiques et reproductibles à la fois dans l’hippocampe et dans l’ensemble du cerveau. Des modalités récentes telles que l’imagerie du tenseur de diffusion ou l’IRM fonctionnelle de repos fournissent des mesures complémentaires qui pourraient également contribuer au diagnostic précoce mais nécessitent d’être plus largement validées

Improved accuracy of the diagnosis of early Alzheimer’s disease using combined measures of hippocampal volume and sulcal morphology

International audienc

Sulcal morphology in Alzheimer's disease: an effective marker of diagnosis and cognition

Julien Lagarde and Fabian Corlier contributed equally.International audienceMeasuring the morphology of brain sulci has been recently proposed as a novel imaging approach in AD. We aimed to investigate the relevance of such an approach in AD, by exploring its (1) clinical relevance in comparison with traditional imaging methods, (2) relationship with amyloid deposition, (3) association with cognitive functions. Here, 51 patients (n=32 MCI/mild dementia-AD, n=19 moderate/severe dementia-AD) diagnosed according to clinical-biological criteria (CSF biomarkers and amyloid-PET) and 29 controls (with negative amyloid-PET) underwent neuropsychological and 3T-MRI examinations. Mean sulcal width (SW) & mean cortical thickness around the sulcus (CT-S) were automatically measured. We found higher SW and lower CT-S in AD patients than in controls. These differences were more pronounced at later stages of the disease and provided the best diagnostic accuracies among the imaging markers. Correlations were not found between CT-S or SW and amyloid deposition but between specific cognitive functions and regional CT-S/SW in key associated regions. Sulcal morphology is a good supporting diagnosis tool, that reflects the main cognitive impairments in AD. It could be considered as a good surrogate marker to evaluate the efficacy of new drugs

L'imagerie par résonance magnétique pour le diagnostic précoce de la maladie d'Alzheimer

International audienceBackground: Previous studies analyzed the ability of hippocampal volumes (HV) to differentiate Alzheimer's disease (AD) from frontotemporal dementia (FTD). However, these studies did not include patients selected according to clinico-biological criteria, using pathophysiological biomarkers. Objective: To analyze the effectiveness of hippocampal volumetric measures to distinguish AD from behavioral variant FTD (bvFTD), using strict inclusion criteria based on clinical and pathophysiological markers. Methods: Seventy-two participants were included: 31 AD patients with predominant and progressive episodic memory deficits associated with typical AD cerebrospinal fluid (CSF) profile and/or positive amyloid imaging (PET with 11C-labeled Pittsburgh Compound B [PiB]), 26 bvFTD patients diagnosed according to consensual clinical criteria and with no AD CSF profile, and 15 healthy controls without amyloid retention on PiB-PET exam. HV were segmented with an automated method and were normalized to total intracranial volume (nHV). Results: Significant reductions in HV were found in both AD and bvFTD patients compared with controls, but there were no significant difference between AD and bvFTD patients. Mean nHV distinguished normal controls from either AD or bvFTD with high sensitivity (80.6% and 76.9%, respectively) and specificity (93.3% for both), but it was inefficient in differentiating AD from bvFTD (9.7% specificity). There was no difference in the clinical and neuropsychological profiles according to HV in bvFTD and AD patients. Conclusions: When considered alone, measures of HV are not good markers to differentiate AD from bvFTD. Hippocampal sclerosis associated with FTD may explain the high degree of overlap in nHV between both groups

L'imagerie par résonance magnétique pour le diagnostic précoce de la maladie d'Alzheimer

International audienceBackground: Previous studies analyzed the ability of hippocampal volumes (HV) to differentiate Alzheimer's disease (AD) from frontotemporal dementia (FTD). However, these studies did not include patients selected according to clinico-biological criteria, using pathophysiological biomarkers. Objective: To analyze the effectiveness of hippocampal volumetric measures to distinguish AD from behavioral variant FTD (bvFTD), using strict inclusion criteria based on clinical and pathophysiological markers. Methods: Seventy-two participants were included: 31 AD patients with predominant and progressive episodic memory deficits associated with typical AD cerebrospinal fluid (CSF) profile and/or positive amyloid imaging (PET with 11C-labeled Pittsburgh Compound B [PiB]), 26 bvFTD patients diagnosed according to consensual clinical criteria and with no AD CSF profile, and 15 healthy controls without amyloid retention on PiB-PET exam. HV were segmented with an automated method and were normalized to total intracranial volume (nHV). Results: Significant reductions in HV were found in both AD and bvFTD patients compared with controls, but there were no significant difference between AD and bvFTD patients. Mean nHV distinguished normal controls from either AD or bvFTD with high sensitivity (80.6% and 76.9%, respectively) and specificity (93.3% for both), but it was inefficient in differentiating AD from bvFTD (9.7% specificity). There was no difference in the clinical and neuropsychological profiles according to HV in bvFTD and AD patients. Conclusions: When considered alone, measures of HV are not good markers to differentiate AD from bvFTD. Hippocampal sclerosis associated with FTD may explain the high degree of overlap in nHV between both groups

Sulcal morphology as a new imaging marker for the diagnosis of early onset Alzheimer's disease

International audienceWe investigated the utility of sulcal width measures in the diagnosis of Alzheimer's disease (AD). Sixty-six biologically confirmed AD patients (positive amyloid positron emission tomography [PET] and/or AD cerebrospinal fluid profile) were contrasted to 35 controls with negative amyloid PET. Patients were classified into prodromal or dementia stages as well as into late onset (LOAD, n = 31) or early onset (EOAD, n = 35) subgroups according to their age of onset. An automated method was used to calculate sulcal widths and hippocampal volumes (HV). In EOAD, the greatest ability to differentiate patients from age-matched controls, regardless of severity, was displayed by sulcal width of the temporoparietal cortex. In this region, diagnosis accuracy was better than the HV, especially at prodromal stage. In LOAD, HV provided the best discrimination power from age-matched controls. In conclusion, sulcal width measures are better markers than the HV for identifying prodromal AD in patients aged <65 years. In contrast, in older patients, the risk of over-diagnosis from using only sulcal enlargement is important