Publications by authors named "Catherine Helmer"

198 Publications

How Selection Over Time Contributes to the Inconsistency of the Association between Sex/Gender and Cognitive Decline across Cognitive Aging Cohorts.

Am J Epidemiol 2021 Sep 14. Epub 2021 Sep 14.

University of Bordeaux, INSERM, Bordeaux Population Health Research Center, U1219, F-33000 Bordeaux, France.

The sex/gender and aging-related cognitive decline association remains poorly understood due to inconsistencies in findings. Such heterogeneity could be attributable to the cognitive functions studied and study population characteristics, but also to a differential selection by drop-out and death between men and women. This work aims to evaluate the impact of selection by drop-out and death on the association between sex/gender and cognitive decline. We first compared the most frequently used statistical methods for longitudinal data, targeting either population estimands (marginal models estimated by Generalized Estimating Equations) or subject-specific estimands (mixed/joint models estimated by likelihood maximization) on eight aging studies: six population-based (ACTIVE(1996-2009), Paquid(1988-2014), REGARDS(2003-2016), 3-City(1999-2016), WHICAP(1992-2017), Whitehall II(2007-2016)) and two clinic-based (ADNI(2004-2017), MEMENTO(2011-2016)) studies. We illustrated the differences in the estimands of the sex/gender association with cognitive decline in selected examples and highlighted the critical role of differential selection by drop-out and death. By using the same estimand, we then contrasted the sex/gender association across cohorts and cognitive measures suggesting residual differential sex/gender association depending on the targeted cognitive measure (memory or animal fluency) and the initial cohort selection. We recommend focusing on subject-specific estimands in the alive population for assessing sex/gender differences while handling differential selection over time.
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http://dx.doi.org/10.1093/aje/kwab227DOI Listing
September 2021

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

JAMA Intern Med 2021 Sep 7. Epub 2021 Sep 7.

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings.

Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.

Design, Setting, And Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021.

Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values.

Main Outcomes And Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated.

Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia.

Conclusions And Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.
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http://dx.doi.org/10.1001/jamainternmed.2021.5078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424529PMC
September 2021

Dynamic reciprocal relationships between cognitive and functional declines along the Alzheimer's disease continuum in the prospective COGICARE study.

Alzheimers Res Ther 2021 09 3;13(1):148. Epub 2021 Sep 3.

Univ. Bordeaux, INSERM, BPH, U1219, F-33000, Bordeaux, France.

Background: Thoroughly understanding the temporal associations between cognitive and functional dimensions along the dementia process is fundamental to define preventive measures likely to delay the disease's onset. This work aimed to finely describe the trajectories of cognitive and functional declines, and assess their dynamic bidirectional relationships among subjects at different stages of the dementia process.

Methods: We leveraged extensive repeated data of cognition and functional dependency from the French prospective COGICARE study, designed to better characterize the natural history of cognitive and functional declines around dementia diagnosis. Cognition was measured by the Mini-Mental State Examination, the Isaacs Set Test for verbal fluency, the Benton Visual Retention Test for visuo-spatial memory, and Trail Making Test Part B for executive functioning. Functional dependency was measured by basic and instrumental activities of daily living. The study included 102 cognitively normal, 123 mildly cognitively impaired, and 72 dementia cases with a median of 5 repeated visits over up to 57 months. We used a dynamic causal model which addresses the two essential issues in temporal associations assessment: focusing on intra-individual change and accounting for time.

Results: Better cognitive abilities were associated with lower subsequent decline of the functional level among the three clinical stages with an intensification over time but no reciprocity of the association whatever the clinical status.

Conclusion: This work confirms that the progressive functional dependency could be induced by cognitive impairment. Subjects identified as early as possible with clinically significant cognitive impairments could benefit from preventive measures before the deterioration of activities of daily living and the appearance of dementia clinical signs.
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http://dx.doi.org/10.1186/s13195-021-00887-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418020PMC
September 2021

Simple carbohydrate intake and higher risk for physical frailty over 15 years in community-dwelling older adults.

J Gerontol A Biol Sci Med Sci 2021 Aug 21. Epub 2021 Aug 21.

Univ. Bordeaux, INSERM, BPH, U1219, Bordeaux, France.

Insulin resistance is a major mechanism involved in the onset of physical frailty (PF). Although rich carbohydrate diets may promote insulin resistance, few studies have examined their association with PF risk. This study aimed to investigate the spectrum of carbohydrate exposure, including carbohydrate intake (simple, complex, and total), glycemic load (measure of the diet-related insulin-demand), and adherence to a low-carbohydrate diet with the incident risk of PF in community-dwelling older adults. Baseline carbohydrate exposure was assessed in non-frail participants of the Three-City-Bordeaux cohort using a 24H dietary recall. Over 15 years of follow-up, participants were screened for PF, defined by the FRAIL scale (≥3 criteria out of Fatigue, Resistance, Ambulation, Illnesses, and weight Loss). Associations were estimated using mixed-effects logistic models adjusted for sex, age, education, smoking status, alcohol consumption, depressive symptomatology, global cognitive performances, and protein and energy intakes. The sample included 1,210 participants (62% females, mean age 76 years). Over the follow-up, 295 (24%) incident cases of PF were documented (28% in females, 18% in males). Higher intake of simple carbohydrates was significantly associated with greater odds of incident PF (per 1-SD increased: OR = 1.29; 95% CI = 1.02-1.62), specifically among males (OR = 1.52; 95% CI = 1.04-2.22). No association was observed with complex or total carbohydrate intake, glycemic load, or low-carbohydrate diet. Among the whole carbohydrate exposure, only higher consumption of simple carbohydrates in older age was associated with a higher risk of developing PF. Further studies are required to explore underlying mechanisms.
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http://dx.doi.org/10.1093/gerona/glab243DOI Listing
August 2021

The serum metabolome mediates the concert of diet, exercise, and neurogenesis, determining the risk for cognitive decline and dementia.

Alzheimers Dement 2021 Aug 17. Epub 2021 Aug 17.

Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Introduction: Diet and exercise influence the risk of cognitive decline (CD) and dementia through the food metabolome and exercise-triggered endogenous factors, which use the blood as a vehicle to communicate with the brain. These factors might act in concert with hippocampal neurogenesis (HN) to shape CD and dementia.

Methods: Using an in vitro neurogenesis assay, we examined the effects of serum samples from a longitudinal cohort (n = 418) on proxy HN readouts and their association with future CD and dementia across a 12-year period.

Results: Altered apoptosis and reduced hippocampal progenitor cell integrity were associated with exercise and diet and predicted subsequent CD and dementia. The effects of exercise and diet on CD specifically were mediated by apoptosis.

Discussion: Diet and exercise might influence neurogenesis long before the onset of CD and dementia. Alterations in HN could signify the start of the pathological process and potentially represent biomarkers for CD and dementia.
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http://dx.doi.org/10.1002/alz.12428DOI Listing
August 2021

Herpes simplex virus, early neuroimaging markers and incidence of Alzheimer's disease.

Transl Psychiatry 2021 07 31;11(1):414. Epub 2021 Jul 31.

University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR U1219, F-33000, Bordeaux, France.

While previous studies suggest the implication of herpes simplex virus (HSV) in the onset of Alzheimer's disease (AD), no study has investigated its association with early neuroimaging markers of AD. In the Three-City and the AMI cohorts, the associations between HSV infection and (i) hippocampal volume (n = 349), (ii) white matter alterations in the parahippocampal cingulum and fornix using diffusion tensor imaging (n = 260), and (iii) incidence of AD (n = 1599) were assessed according to APOE4 status. Regardless of APOE4 status, infected subjects presented (i) significantly more microstructural alterations of the parahippocampal cingulum and fornix, (ii) lower hippocampal volumes only when their anti-HSV IgG level was in the highest tercile-reflecting possibly more frequent reactivations of the virus (p = 0.03 for subjects with a high anti-HSV IgG level while there was no association for all infected subjects, p = 0.19), and (iii) had no increased risk of developing AD. Nevertheless, among APOE4 carriers, infected subjects presented lower hippocampal volumes, although not significant (p = 0.09), and a two or three times higher risk of developing AD (adjusted Hazard ratio (aHR) = 2.72 [1.07-6.91] p = 0.04 for infected subjects and aHR = 3.87 [1.45-10.28] p = 0.007 for infected subjects with an anti-HSV IgG level in the highest tercile) while no association was found among APOE4 noncarriers. Our findings support an association between HSV infection and AD and a potential interaction between HSV status and APOE4. This reinforces the need to further investigate the infectious hypothesis of AD, especially the associated susceptibility factors and the possibility of preventive treatments.
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http://dx.doi.org/10.1038/s41398-021-01532-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325675PMC
July 2021

Vision Impairment and Adverse Health Conditions in Congolese Older People: A Population-Based Study.

Gerontology 2021 Jul 27:1-10. Epub 2021 Jul 27.

INSERM, IRD, U1094 Tropical Neuroepidemiology, Institute of Epidemiology and Tropical Neurology, GEIST, University of Limoges, Limoges, France.

Introduction: In sub-Saharan Africa, many older people experience vision impairment (VI) and its adverse health outcomes. In this study, we examined separately the association between VI and each adverse health conditions (cognitive disorders, vision-related quality of life [VRQoL], and daily functioning interference [DFI]) among Congolese older people. We also explored whether VI had a significant effect on VRQoL components in our population.

Method: We performed cross-sectional analyses on data from 660 Congolese people aged ≥65 years who participated in the 2013 survey of the EPIDEMCA population-based cohort study. VI was defined as having a near visual acuity <20/40 (assessed at 30 cm using a Parinaud chart). Cognitive disorders were assessed using neuropsychological tests and neurological examinations. VRQoL was assessed using a reduced version of the National Eye Institute Visual Function Questionnaire (VFQ-22) and DFI using 11 items of participation restrictions and activity limitations. Regarding our main objective, each association was explored separately using multivariable logistic and linear regression models. Additionally, the effects of VI on each VRQoL components were explored using univariable linear regression models.

Results: VI was not associated with cognitive disorders after adjustment for residence area (adjusted odds ratio = 1.7; 95% confidence interval [CI]: 0.6; 4.7), but it was associated with a low VRQoL score (adjusted β = -12.4; 95% CI: -17.5; -7.3) even after controlling for several covariates. An interaction between VI and age (p = 0.007) was identified, and VI was associated with DFI only among people aged >73 years (adjusted β = 0.5; 95% CI: 0.2; 0.8). Our exploratory analysis showed that all components of VRQoL decreased with a decrease in visual acuity (corrected p ≤ 0.05).

Conclusion: VI was associated with poor VRQoL and high DFI. Residence area seems to play a confounding role in the association between VI and cognitive disorders. Our findings suggest that targeting interventions on vision could reduce DFI among older people and improve their well-being.
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http://dx.doi.org/10.1159/000517044DOI Listing
July 2021

Dairy Product Intake and Long-Term Risk for Frailty among French Elderly Community Dwellers.

Nutrients 2021 Jun 23;13(7). Epub 2021 Jun 23.

Institut National de la Santé et de la Recherche Médicale (INSERM), University Bordeaux, INSERM, BPH, U1219, F-33000 Bordeaux, France.

Dairy products (DP) are part of a food group that may contribute to the prevention of physical frailty. We aimed to investigate DP exposure, including total DP, milk, fresh DP and cheese, and their cross-sectional and prospective associations with physical frailty in community-dwelling older adults. The cross-sectional analysis was carried out on 1490 participants from the Three-City Bordeaux cohort. The 10-year frailty risk was examined in 823 initially non-frail participants. A food frequency questionnaire was used to assess DP exposure. Physical frailty was defined as the presence of at least 3 out of 5 criteria of the frailty phenotype: weight loss, exhaustion, slowness, weakness, and low physical activity. Among others, diet quality and protein intake were considered as confounders. The baseline mean age of participants was 74.1 y and 61% were females. Frailty prevalence and incidence were 4.2% and 18.2%, respectively. No significant associations were observed between consumption of total DP or DP sub-types and frailty prevalence or incidence (OR = 1.40, 95%CI 0.65-3.01 and OR = 1.75, 95%CI 0.42-1.32, for a total DP consumption >4 times/d, respectively). Despite the absence of beneficial associations of higher DP consumption on frailty, older adults are encouraged to follow the national recommendations regarding DP.
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http://dx.doi.org/10.3390/nu13072151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308304PMC
June 2021

ADL-dependent older adults were identified in medico-administrative databases.

J Clin Epidemiol 2021 Jun 21. Epub 2021 Jun 21.

DRUGS-SAFE National Platform of Pharmacoepidemiology, Bordeaux, France; Univ. Bordeaux, Inserm UMR 1219, Bordeaux Population Health Research Center, team Psychoepidemiology of aging and chronic diseases, France.

Objective: We aimed to develop an algorithm for the identification of basic Activities of Daily Living (ADL)-dependency in health insurance databases.

Study Design And Setting: We used the AMI (Aging Multidisciplinary Investigation) population-based cohort including both individual face-to-face assessment of ADL-dependency and merged health insurance data. The health insurance factors associated with ADL-dependency were identified using a LASSO logistic regression model in 1000 bootstrap samples. An external validation on a 1/97 representative sample of the French Health Insurance general population of Affiliates has been performed.

Results: Among 995 participants of the AMI cohort aged ≥ 65y, 114 (11.5%) were ADL-dependent according to neuropsychologists individual assessments. The final algorithm developed included: age, sex, four drug classes (dopaminergic antiparkinson drugs, antidepressants, antidiabetic agents, lipid modifying agents), three type of medical devices (medical bed, patient lifter, incontinence equipment), four medical acts (GP's consultations at home, daily and non-daily nursing at home, transport by ambulance) and four long-term diseases (stroke, heart failure, coronary heart disease, Alzheimer and other dementia). Applying this algorithm, the estimated prevalence of ADL-dependency was 12.3% in AMI and 9.5% in the validation sample.

Conclusion: This study proposes a useful algorithm to identify ADL-dependency in the health insurance data.
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http://dx.doi.org/10.1016/j.jclinepi.2021.06.014DOI Listing
June 2021

Associations between physical activity types and multi-domain cognitive decline in older adults from the Three-city cohort.

PLoS One 2021 1;16(6):e0252500. Epub 2021 Jun 1.

Institute for Neurosciences of Montpellier, Inserm, Univ. Montpellier, Montpellier, France.

Several studies suggest that physical activity improves cognitive functions and reduces cognitive decline, whereas others did not find any evidence of a neuroprotective effect. Furthermore, few cohort studies have analyzed the different physical activity types and particularly household activities. Our objective was to assess the association of two physical activity types with the decline in different cognitive domains in a large prospective cohort of community-dwelling older adults from the Three-city study. Physical activity (domestic/transportation activities and leisure/sport activities) was assessed with the Voorrips questionnaire, specific for older adults. Baseline sociodemographic and health history variables as well as cognitive performance data at baseline and during the 8-year follow-up (Mini-Mental State Examination, Benton Visual Retention Test, Trail Making Tests A and B, Isaac's Set Test and Free and Cued Selective Reminding Test) were also available. Associations between physical activity scores and cognitive decline in different domains were tested using minimally- and multi-adjusted linear mixed models. The analysis included 1697 participants without dementia at baseline and with at least one follow-up visit. At baseline, participants with higher sub-scores for the two physical activity types had better cognitive performances. Interaction with time showed that decline in some cognitive scores (Trail Making Test B and Isaac's Set Test) was significantly less pronounced in participants with higher household/transportation activity sub-scores. No significant effect over time was found for leisure/sport activities. This study shows that during an 8-year follow-up, executive functions and verbal fluency were better preserved in older adults who performed household/transportation activities at moderate to high level. Participation in domestic activities and using adapted transport means could allow older adults to maintain specific cognitive abilities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252500PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168837PMC
June 2021

Mediterranean diet and prudent diet are both associated with low circulating esterified 3-hydroxy fatty acids, a proxy of LPS burden, among older adults.

Am J Clin Nutr 2021 09;114(3):1080-1091

Université de Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health, U1219, Bordeaux, France.

Background: LPS-type endotoxins, naturally found in the gut microbiota, are recognized as triggers of inflammation and emerge as detrimental factors of healthy aging. Nutrition represents a promising strategy to reduce LPS burden, yet little is known about the relation of diet to circulating LPS concentrations.

Objective: The aim was to evaluate the associations between food groups, dietary patterns, and circulating 3-hydroxy fatty acids (3-OH FAs), a proxy of LPS burden.

Methods: In a cross-sectional study of 698 French older community-dwelling individuals, 3-OH FA concentrations were measured by LC-tandem MS. Dietary patterns were determined using food-frequency questionnaires. Adherence to a Mediterranean-type diet was computed according to the consumption of 8 food groups (fruits, vegetables, legumes, cereals, fish, olive oil, meat, and dairy products) and alcohol intake (range: 0, low adherence, to 18, high adherence). Three a posteriori dietary patterns were derived from factor analysis: complex carbohydrate (rich in rice, pasta, eggs, poultry, and potatoes), traditional (rich in alcohol, meat, processed meats-cold cuts, and legumes), and prudent (rich in vegetables and fruits and low in cookies) diets. Linear regression models were applied.

Results: The frequency of consumption of each food group was not associated with 3-OH FA concentrations. Greater adherence to both the Mediterranean diet and the prudent diet were associated with lower circulating 3-OH FAs (β [95% CI] for each additional point of score: -0.12 [-0.22, -0.01] and -0.27 [-0.48, -0.07], respectively). In contrast, greater adherence to the traditional diet was associated with higher concentration of 3-OH FAs (β [95% CI] 0.22 [0.001, 0.46]). The adherence to the complex-carbohydrate diet was not associated with 3-OH FA concentrations.

Conclusions: Based on 2 complementary approaches, the identified plant-based dietary patterns were associated with lower 3-OH FA concentrations, and thus a lower LPS burden, which is considered a potent trigger of inflammatory response.
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http://dx.doi.org/10.1093/ajcn/nqab126DOI Listing
September 2021

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

Nat Commun 2021 04 22;12(1):2329. Epub 2021 Apr 22.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
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http://dx.doi.org/10.1038/s41467-021-22370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062567PMC
April 2021

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies.

Diabetes Care 2021 05 3;44(5):1133-1142. Epub 2021 Mar 3.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

Research Design And Methods: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.

Results: A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.

Conclusions: Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
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http://dx.doi.org/10.2337/dc20-2426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132316PMC
May 2021

Distinct Hippocampal Subfields Atrophy in Older People With Vascular Brain Injuries.

Stroke 2021 May 4;52(5):1741-1750. Epub 2021 Mar 4.

University of Bordeaux, CNRS, UMR 5293, Institut des Maladies Neurodégénératives, France (G.P., L.N., B.M., V.P.).

Background And Purpose: Many neurological or psychiatric diseases affect the hippocampus during aging. The study of hippocampal regional vulnerability may provide important insights into the pathophysiological mechanisms underlying these processes; however, little is known about the specific impact of vascular brain damage on hippocampal subfields atrophy.

Methods: To analyze the effect of vascular injuries independently of other pathological conditions, we studied a population-based cohort of nondemented older adults, after the exclusion of people who were diagnosed with neurodegenerative diseases during the 14-year clinical follow-up period. Using an automated segmentation pipeline, 1.5T-magnetic resonance imaging at inclusion and 4 years later were assessed to measure both white matter hyperintensities and hippocampal subfields volume. Annualized rates of white matter hyperintensity progression and annualized rates of hippocampal subfields atrophy were then estimated in each participant.

Results: We included 249 participants in our analyses (58% women, mean age 71.8, median Mini-Mental State Evaluation 29). The volume of the subiculum at baseline was the only hippocampal subfield volume associated with total, deep/subcortical, and periventricular white matter hyperintensity volumes, independently of demographic variables and vascular risk factors (β=-0.17, =0.011; β=-0.25, =0.020 and β=-0.14, =0.029, respectively). In longitudinal measures, the annualized rate of subiculum atrophy was significantly higher in people with the highest rate of deep/subcortical white matter hyperintensity progression, independently of confounding factors (β=-0.32, =0.014).

Conclusions: These cross-sectional and longitudinal findings highlight the links between vascular brain injuries and a differential vulnerability of the subiculum within the hippocampal loop, unbiased of the effect of neurodegenerative diseases, and particularly when vascular injuries affect deep/subcortical structures.
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http://dx.doi.org/10.1161/STROKEAHA.120.031743DOI Listing
May 2021

A robust machine learning framework to identify signatures for frailty: a nested case-control study in four aging European cohorts.

Geroscience 2021 06 18;43(3):1317-1329. Epub 2021 Feb 18.

German Institute for Human Nutrition, Potsdam, Germany.

Phenotype-specific omic expression patterns in people with frailty could provide invaluable insight into the underlying multi-systemic pathological processes and targets for intervention. Classical approaches to frailty have not considered the potential for different frailty phenotypes. We characterized associations between frailty (with/without disability) and sets of omic factors (genomic, proteomic, and metabolomic) plus markers measured in routine geriatric care. This study was a prevalent case control using stored biospecimens (urine, whole blood, cells, plasma, and serum) from 1522 individuals (identified as robust (R), pre-frail (P), or frail (F)] from the Toledo Study of Healthy Aging (R=178/P=184/F=109), 3 City Bordeaux (111/269/100), Aging Multidisciplinary Investigation (157/79/54) and InCHIANTI (106/98/77) cohorts. The analysis included over 35,000 omic and routine laboratory variables from robust and frail or pre-frail (with/without disability) individuals using a machine learning framework. We identified three protective biomarkers, vitamin D3 (OR: 0.81 [95% CI: 0.68-0.98]), lutein zeaxanthin (OR: 0.82 [95% CI: 0.70-0.97]), and miRNA125b-5p (OR: 0.73, [95% CI: 0.56-0.97]) and one risk biomarker, cardiac troponin T (OR: 1.25 [95% CI: 1.23-1.27]). Excluding individuals with a disability, one protective biomarker was identified, miR125b-5p (OR: 0.85, [95% CI: 0.81-0.88]). Three risks of frailty biomarkers were detected: pro-BNP (OR: 1.47 [95% CI: 1.27-1.7]), cardiac troponin T (OR: 1.29 [95% CI: 1.21-1.38]), and sRAGE (OR: 1.26 [95% CI: 1.01-1.57]). Three key frailty biomarkers demonstrated a statistical association with frailty (oxidative stress, vitamin D, and cardiovascular system) with relationship patterns differing depending on the presence or absence of a disability.
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http://dx.doi.org/10.1007/s11357-021-00334-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190217PMC
June 2021

Plasma carotenoids and medial temporal lobe atrophy in older adults.

Clin Nutr 2021 04 14;40(4):2460-2463. Epub 2020 Oct 14.

Univ. Bordeaux, INSERM, BPH, U1219, F-33000, Bordeaux, France.

Background & Aims: Carotenoids are vegetable pigments with neuroprotective properties. Clinical studies found efficacy of specific carotenoids on improving brain perfusion and functioning with aging. However, evidence of an effect on neurodegeneration, which may require longer follow-up period to observe, is more limited. Leveraging biomarkers from a large population-based cohort study of older adults, we investigated whether blood carotenoids were associated with atrophy of the medial temporal lobe (a biomarker of neurodegeneration in aging) over 10 years.

Methods: This study included 461 dementia-free participants from the Three-City Bordeaux study (aged ≥65) who had plasma carotenoids measured at baseline and up to three repeated brain imaging exams in the subsequent 10 years.

Results: In adjusted linear mixed models, each increase of 1 SD in plasma level of total carotenoids and of β-carotene was associated with 0.02 cm (95% CI, 0.001-0.04; P = 0.04) and 0.02 cm (95% CI, 0.01-0.04; P = 0.008) smaller medial temporal lobe volume loss per year, respectively.

Conclusions: Our results based on a unique long-term prospective evaluation of a neuroimaging biomarker suggest a beneficial role of carotenoids for the prevention of age-related neurodegeneration.
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http://dx.doi.org/10.1016/j.clnu.2020.09.056DOI Listing
April 2021

Similarities in cognitive abilities in older couples: a study of mutual influences.

J Clin Exp Neuropsychol 2021 02 8;43(1):78-90. Epub 2021 Feb 8.

Bordeaux Population Health Research Center, Univ. Bordeaux, Inserm, UMR 1219, Bordeaux, France.

: Similarities between spouses in cognitive functions have been mainly explained by the assortative mating phenomenon and the convergence for age and education. The mutual influence between spouses is another explanation particularly relevant in the elderly population. Today, it remains difficult to determine whether cognitive similarities exclusively result from the convergence effect or from the mutual influence. Using a novel methodology, the present study aimed to assess the impact of the marital relationship on cognitive similarities among elderly couples.: 1723 couples from the Three-City Cohort Study were classified in two groups of couples with homogeneous and heterogeneous age and education. We also constituted two groups of pseudo-couples by a random association of individuals, with homogeneous and heterogeneous age and education. Dyadic analyses were conducted in the four groups, regarding the similarities in lexicosemantic abilities, executive functions, memory and global cognitive functioning.: Similarities were found on lexicosemantic abilities both in mate-assorted couples and in couples heterogeneous in age and education but no similarity was found in pseudo-couples.: Beyond the convergence effect, the fact that the spouses co-construct their lifestyles may contribute to cognitive similarities in the lexicosemantic domain.
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http://dx.doi.org/10.1080/13803395.2021.1874882DOI Listing
February 2021

Early signature in the blood lipidome associated with subsequent cognitive decline in the elderly: A case-control analysis nested within the Three-City cohort study.

EBioMedicine 2021 Feb 25;64:103216. Epub 2021 Jan 25.

University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, France. Electronic address:

Background: Brain lipid metabolism appears critical for cognitive aging, but whether alterations in the lipidome relate to cognitive decline remains unclear at the system level.

Methods: We studied participants from the Three-City study, a multicentric cohort of older persons, free of dementia at time of blood sampling, and who provided repeated measures of cognition over 12 subsequent years. We measured 189 serum lipids from 13 lipid classes using shotgun lipidomics in a case-control sample on cognitive decline (matched on age, sex and level of education) nested within the Bordeaux study center (discovery, n = 418). Associations with cognitive decline were investigated using bootstrapped penalized regression, and tested for validation in the Dijon study center (validation, n = 314).

Findings: Among 17 lipids identified in the discovery stage, lower levels of the triglyceride TAG50:5, and of four membrane lipids (sphingomyelin SM40:2,2, phosphatidylethanolamine PE38:5(18:1/20:4), ether-phosphatidylethanolamine PEO34:3(16:1/18:2), and ether-phosphatidylcholine PCO34:1(16:1/18:0)), and higher levels of PCO32:0(16:0/16:0), were associated with greater odds of cognitive decline, and replicated in our validation sample.

Interpretation: These findings indicate that in the blood lipidome of non-demented older persons, a specific profile of lipids involved in membrane fluidity, myelination, and lipid rafts, is associated with subsequent cognitive decline.

Funding: The complete list of funders is available at the end of the manuscript, in the Acknowledgement section.
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http://dx.doi.org/10.1016/j.ebiom.2021.103216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841305PMC
February 2021

Long-term exposure to ambient air pollution and risk of dementia: Results of the prospective Three-City Study.

Environ Int 2021 03 20;148:106376. Epub 2021 Jan 20.

INM, Univ Montpellier, Inserm, Montpellier, France.

Background: Emerging epidemiological evidence suggests a relationship between exposure to air pollution and dementia. However, most of the existing studies relied on health administrative databases for the diagnosis of dementia. In a large French population-based cohort (the 3C Study), we assessed the effects of particulate matter ≤2.5 µm (PM2.5), nitrogen dioxide (NO) and black carbon (BC) on the risk of dementia diagnosed with reliable tools.

Methods: Participants aged ≥65 years were recruited between 1999 and 2001 and followed for 12 years. At baseline and every 2 years, dementia was suspected on the basis of the neuropsychological and neurological examination and confirmed by an independent committee of clinicians. Exposure to NO, BC and PM2.5 at the participants' residential address was estimated using land use regression models. For each pollutant and year of follow-up, the 10-year moving average of past exposure was estimated. Multilevel spatial random-effects Cox proportional hazards models were used in which exposure was included as a time-varying variable. Analyses were adjusted for individual (age, sex, education, APOE4 genotype, health behaviours) and contextual (neighbourhood deprivation index) confounders.

Results: At baseline, the median age of the 7066 participants was 73.4 years, and 62% were women. The median follow-up duration was 10.0 years during which 791 participants developed dementia (n = 541 Alzheimer's disease (AD) and n = 155 vascular/mixed dementia (VaD)). The 10-year moving average of PM2.5 concentrations ranged from 14.6 to 31.3 µg/m. PM2.5 concentration was positively associated with dementia risk: HR = 1.20, 95% CI (1.08-1.32) for all-cause dementia, 1.20 (1.09-1.32) for AD, and 1.33 (1.05-1.68) for VaD per 5 µg/m PM2.5 increase. No association was detected between NO or BC exposure and dementia risk.

Conclusion: In this large cohort of older adults, long-term PM2.5 exposure was associated with increased dementia incidence. Reducing PM2.5 emissions might lessen the burden of dementia in aging populations.
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http://dx.doi.org/10.1016/j.envint.2020.106376DOI Listing
March 2021

Cardiovascular Health and Near Visual Impairment Among Older Adults in the Republic of Congo: A Population-Based Study.

J Gerontol A Biol Sci Med Sci 2021 04;76(5):842-850

INSERM, Univ. Limoges, IRD, U1094 Tropical Neuroepidemiology, Institute of Epidemiology and Tropical Neurology, GEIST, Limoges, France.

Background: Visual impairment (VI) and determinants of poor cardiovascular health are very common in Sub-Saharan Africa. However, we do not know whether these determinants are associated with VI among older adults in this region. This study aimed at investigating the association between the determinants of poor cardiovascular health and near VI among older adults living in Congo.

Methods: Participants were Congolese adults aged 65 or older included in Epidemiology of Dementia in Central Africa-Follow-up population-based cohort. Near VI was defined as visual acuity less than 20/40 measured at 30 cm. Associations between determinants of poor cardiovascular health collected at baseline and near visual acuity measured at first follow-up were investigated using multivariable logistic regression models.

Results: Among the 549 participants included, 378 (68.8%; 95% confidence interval [CI]: 64.9%-72.7%]) had near VI. Of the determinants of poor cardiovascular health explored, we found that having high body mass index of at least 25 kg/m2 (odds ratio [OR] = 2.15; 95% CI: 1.25-3.68), diabetes (OR = 2.12; 95% CI: 1.06-4.25) and hypertension (OR = 1.65; 95% CI: 1.02-2.64) were independently associated with near VI.

Conclusions: Several determinants of poor cardiovascular health were associated with near VI in this population. This study suggests that promoting good cardiovascular health could represent a target for VI prevention among older adults.
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http://dx.doi.org/10.1093/gerona/glaa304DOI Listing
April 2021

Free water: A marker of age-related modifications of the cingulum white matter and its association with cognitive decline.

PLoS One 2020 20;15(11):e0242696. Epub 2020 Nov 20.

EPHE, PSL, Bordeaux, France.

Diffusion MRI is extensively used to investigate changes in white matter microstructure. However, diffusion measures within white matter tissue can be affected by partial volume effects due to cerebrospinal fluid and white matter hyperintensities, especially in the aging brain. In previous aging studies, the cingulum bundle that plays a central role in the architecture of the brain networks supporting cognitive functions has been associated with cognitive deficits. However, most of these studies did not consider the partial volume effects on diffusion measures. The aim of this study was to evaluate the effect of free water elimination on diffusion measures of the cingulum in a group of 68 healthy elderly individuals. We first determined the effect of free water elimination on conventional DTI measures and then examined the effect of free water elimination on verbal fluency performance over 12 years. The cingulum bundle was reconstructed with a tractography pipeline including a white matter hyperintensities mask to limit the negative impact of hyperintensities on fiber tracking algorithms. We observed that free water elimination increased the ability of conventional DTI measures to detect associations between tissue diffusion measures of the cingulum and changes in verbal fluency in older individuals. Moreover, free water content and mean diffusivity measured along the cingulum were independently associated with changes in verbal fluency. This suggests that both tissue modifications and an increase in interstitial isotropic water would contribute to cognitive decline. These observations reinforce the importance of using free water elimination when studying brain aging and indicate that free water itself could be a relevant marker for age-related cingulum white matter modifications and cognitive decline.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242696PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678997PMC
January 2021

Blood polyunsaturated omega-3 fatty acids, brain atrophy, cognitive decline, and dementia risk.

Alzheimers Dement 2020 Oct 8. Epub 2020 Oct 8.

INSERM, BPH, U1219, Univ. Bordeaux, Bordeaux, F-33000, France.

Introduction: We searched for consistent associations of an omega-3 index in plasma (sum of eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) with several dementia-related outcomes in a large cohort of older adults.

Methods: We included 1279 participants from the Three-City study, non-demented at the time of blood measurements at baseline, with face-to-face neuropsychological assessment and systematic detection of incident dementia over a 17-year follow-up. An ancillary study included 467 participants with up to three repeated brain imaging exams over 10 years.

Results: In multivariable models, higher levels of plasma EPA+DHA were consistently associated with a lower risk of dementia (hazard ratio for 1 standard deviation = 0.87 [95% confidence interval, 0.76-0.98]), and a lower decline in global cognition (P = .04 for change over time), memory (P = .06), and medial temporal lobe volume (P = .02).

Discussion: This prospective study provides compelling evidence for a relationship between long-chain omega-3 fatty acids levels and lower risks for dementia and related outcomes.
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http://dx.doi.org/10.1002/alz.12195DOI Listing
October 2020

Study of mutual influence between trait anxiety and risk of depression among older couples facing cancer.

J Geriatr Oncol 2021 05 29;12(4):605-611. Epub 2020 Sep 29.

University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo Saignat, CS61292, F-33076 Bordeaux Cedex, France. Electronic address:

Introduction: The present study aims to examine the process of mutual influence in older couples with cancer diagnosis by studying their risk of depression.

Materials And Methods: 282 couples with one spouse diagnosed with cancer were selected from the Three-City cohort study. Dyadic analyses were used to determine whether trait anxiety affects the risk of depression and whether a mutual influence process occurs prior and post cancer diagnosis. Cross-sectional analyses were performed at two time-points: before and after receiving the diagnosis.

Results: A higher level of anxiety among cancer patients resulted in a decreased risk of depression among spousal caregivers. Moreover, a higher anxiety among spousal caregivers increased their own risk of depression, but it didn't influence depression risk among cancer patients. While there is an intra-individual relationship between a higher level of trait anxiety and a greater risk of depression prior to cancer diagnosis, there is no cross-influence between spouses.

Discussion: The study findings indicate that a dyadic psychological adjustment process might help older adults to cope with cancer by limiting the risk of depression among spousal caregivers.
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http://dx.doi.org/10.1016/j.jgo.2020.09.017DOI Listing
May 2021

Changes Over Time of Diffusion MRI in the White Matter of Aging Brain, a Good Predictor of Verbal Recall.

Front Aging Neurosci 2020 14;12:218. Epub 2020 Aug 14.

Université de Bordeaux, INCIA, UMR 5287-équipe NeuroImagerie et Cognition Humaine, Bordeaux, France.

: Extensive research using water-diffusion MRI reported age-related modifications of cerebral White Matter (WM). Moreover, water-diffusion parameter modifications have been frequently associated with cognitive performances in the elderly sample, reinforcing the idea of aging inducing microstructural disconnection of the brain which in turn impacts cognition. However, only few studies really assessed over-time modifications of these parameters and their relationship with episodic memory outcome of elderly. : One-hundred and thirty elderly subjects without dementia (74.1 ± 4.1 years; 47% female) were included in this study. Diffusion tensor imaging (DTI) was performed at two-time points (3.49 ± 0.68 years apart), allowing the assessment of changes in water-diffusion parameters over time using a specific longitudinal pipeline. White matter hyperintensity (WMH) burden and gray matter (GM) atrophy were also measured on FLAIR and T1-weighted sequences collected during these two MRI sessions. Free and cued verbal recall scores assessed at the last follow-up of the cohort were used as episodic memory outcome. Changes in water-diffusion parameters over time were included in serial linear regression models to predict retrieval or storage ability of elderly. : GM atrophy and an increase in mean diffusivity (MD) and WMH load between the two-time points were observed. The increase in MD was significantly correlated with WMH load and the different memory scores. In models accounting for the baseline cognitive score, GM atrophy, or WMH load, MD changes still significantly predict free verbal recall, and not total verbal recall, suggesting the specific association with the retrieval deficit in healthy aging. : In elderly, microstructural WM changes are good predictors of lower free verbal recall performances. Moreover, this contribution is not only driven by WMH load increase. This last observation is in line with studies reporting early water-diffusion modification in WM tissue during aging, resulting lately in the appearance of WMH on conventional MRI.
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http://dx.doi.org/10.3389/fnagi.2020.00218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456903PMC
August 2020

Association between visual impairment and cognitive disorders in low-and-middle income countries: a systematic review.

Aging Ment Health 2021 10 8;25(10):1786-1795. Epub 2020 Sep 8.

INSERM U 1094 Institute of Epidemiology and Tropical Neurology, University of Limoges, Limoges, France.

Objectives: Visual impairment and cognitive disorders are common among older people in Low-and Middle-Income Countries (LMIC). Several recent studies performed in High-Income Countries suggested that visual impairment is associated with cognitive disorders. However, no synthesis of current knowledge exists for LMIC.

Methods: We have conducted an extensive literature search combining six databases and two grey literature databases. We searched for studies assessing the link between visual and cognitive impairments carried out in LMIC. The systematic search was performed up to 14th February 2019.

Results: Overall, eight studies were included in this review. Among them, five studies were performed in Asia and seven studies had a cross-sectional design. Mean age of the participants varied from 64.2 to 76.2 years. Participants were most often females. Only three studies were specifically focused on the association between visual impairment and cognitive disorders. Out of the eight studies included, four reported a significant association; two showed a possible association and two did not retrieve any statistically significant effect. Heterogeneity in assessments of visual and cognitive impairments was high.

Conclusion: In LMIC, very few studies explored the association between visual and cognitive impairments among older people. The current review seems to suggest that visual impairment is associated with cognitive disorders in LMIC. However, further studies are required to improve the knowledge on this relationship. Improving vision, in particular through optical correction and cataract surgery, could potentially be easy pathways to reduce cognitive disorders incidence and to improve quality of life of people affected by this disorder.
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http://dx.doi.org/10.1080/13607863.2020.1808878DOI Listing
October 2021

Impact of benzodiazepine consumption reduction on future burden of dementia.

Sci Rep 2020 09 4;10(1):14666. Epub 2020 Sep 4.

INSERM, ISPED, Bordeaux Population Health Research Center, UMR 1219, Univ. Bordeaux, Bordeaux, France.

Dementia is a major public health issue worldwide and chronic use of benzodiazepine, which is very frequent in northern countries, was found to be a risk factor of dementia. This work aims at evaluating the impact of a reduction in chronic use of benzodiazepine on the future burden of dementia in France. Using estimations of dementia incidence and of benzodiazepine use and nation-wide projections of mortality and population sizes, a Monte Carlo approach based on an illness-death model provided projections of several indicators of dementia burden. With no change in benzodiazepine consumption, the prevalence of dementia between age 65 and 99 in France in 2040 was estimated at 2.16 millions (95% confidence interval (CI) 1.93-2.38), with a life expectancy without dementia at 65 years equal to 25.0 years (24.7-25.3) for women and 23.8 years (23.5-24.2) for men. Assuming a disappearance of chronic use of benzodiazepine in 2020, the prevalence would be reduced by about 6.6% in 2040 and the life expectancy without dementia would increase by 0.99 (0.93-1.06) year among women and 0.56 (0.50-0.62) among men. To conclude, a modest but significant reduction in future dementia burden could be obtained by applying current recommendation for duration of benzodiazepine use.
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http://dx.doi.org/10.1038/s41598-020-71482-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474098PMC
September 2020

Cognitive and functional changes in prediagnostic phase of Parkinson disease: A population-based study.

Parkinsonism Relat Disord 2020 Aug 15;79:40-46. Epub 2020 Aug 15.

Institut des Maladies Neurodégénératives-Clinique (IMNc), University Hospital Bordeaux, Bordeaux, France; Institut des Maladies Neurodégénératives, CNRS, UMR 5293, Bordeaux University, Bordeaux, France.

Introduction: Prodromal non-motor symptoms precede, often by decades, motor signs and diagnosis of Parkinson's disease. It is however still uncertain if cognitive changes belong to the spectrum of non-motor prodromal Parkinson's disease. Thanks to the very long-term follow-up of the PAQUID population-based cohort, we assessed trajectories of cognitive complaints and functioning over a 13-year period before the diagnosis of late onset Parkinson's disease.

Methods: This study relies on a matched nested case-control sample selected from the cohort. Of the 3777 initial subjects of the cohort, 43 developed incident Parkinson's disease over the follow-up. The mean age at diagnosis was 78.0 (standard deviation = 5.8) years and 46.5% were men. These cases were matched to 86 elderly control subjects. Scores of different cognitive domains, daily function, and depressive symptoms were described throughout the follow-up using mixed-effects models.

Results: No significant global cognitive decline preceded the diagnosis of late onset Parkinson's disease. However, psychomotor speed appeared significantly slower 2 years before the diagnosis and depressive symptoms 12 years before. Global score of instrumental activities of daily living became altered 2-3 years preceding the diagnosis of late onset Parkinson's disease, including the use of public transportation that was altered ten years before the diagnosis.

Conclusion: In late onset Parkinson's disease, while global cognitive functions seem preserved, psychomotor speed starts to decline 2 years before the diagnosis and activities of daily living are also impacted. Depressive symptoms appear very early in the prediagnosic phase.
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http://dx.doi.org/10.1016/j.parkreldis.2020.08.022DOI Listing
August 2020

Age-related change in episodic memory: role of functional and structural connectivity between the ventral posterior cingulate and the parietal cortex.

Brain Struct Funct 2020 Sep 29;225(7):2203-2218. Epub 2020 Jul 29.

EPHE, PSL, 33000, Bordeaux, France.

While the neural correlates of age-related episodic memory decline have been extensively studied, the precise involvement of the Posterior Cingulate Cortex (PCC) and posterior parietal cortex (the precuneus and the angular gyrus), remains unclear. The present study examined functional and structural neural correlates of age-related episodic memory change assessed over 12 years in 120 older adults (range 76-90 years). Episodic memory performance was measured using the Free and Cued Selective Reminding Test (FCSRT); functional connectivity metrics were computed from resting-state fMRI images and structural connectivity metrics were assessed through microstructural properties of reconstructed tract using a native space pipeline. We found that FCSRT change was significantly associated with the functional connectivity between the ventral PCC and three parietal regions, the ventral superior, the inferior part of the precuneus, and the rostro dorsal part of the angular gyrus. This association was independent of hippocampal volume. In addition, we found the that change in FCSRT scores was associated with fractional anisotropy of the tract connecting the ventral PCC and the ventral superior part of the precuneus. Change in episodic memory in aging was therefore related to a combination of high functional connectivity and low structural connectivity between the ventral PCC and the ventral superior part of the precuneus.
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http://dx.doi.org/10.1007/s00429-020-02121-7DOI Listing
September 2020

Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium.

Neurology 2020 08 1;95(5):e519-e531. Epub 2020 Jul 1.

From the Department of Epidemiology (F.J.W., L.B.C., R.W., D. Blacker, D. Bos, J.G., A.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Departments of Epidemiology (F.J.W., D. Bos, S.K.L.D., M.A.I., M.K.I., A.H.), Radiology and Nuclear Medicine (D. Bos), and Neurology (M.K.I.), Erasmus MC, Rotterdam, the Netherlands; Department of Neurology (L.B.C.), Massachusetts General Hospital, Boston; Department of Infectious Disease Epidemiology (R.A., F.d.W., C. Hadjichrysanthou, K.M.-M., M.M.W.), School of Public Health, Imperial College London, UK; Neuropsychiatry and Epidemiology and Clinical Research (C. Berr), INSERM, UMR 1061 Montpellier, Universite de Montpellier, France; Boston University School of Medicine (A.B., M.P.P., C.L.S., S.S.); Framingham Heart Study (A.B., M.P.P., C.L.S., S.S.), MA; Department of Biostatistics (A.B., K.L.D.-P.), Boston University School of Public Health, MA; Cardiovascular Health Research Unit, Departments of Medicine (J.C.B., B.M.P.) and Epidemiology and Health Services (B.M.P.), University of Washington, Seattle; Department of Psychiatry (D. Blacker), Massachusetts General Hospital, Charlestown; University of Cambridge (C. Brayne), UK; Bordeaux Population Health Research Center (J.-F.D., S.D., C.D., L.G., C. Helmer), INSERM, UMR 1219, University of Bordeaux; Department of Neurology (S.D.), Memory Clinic, Bordeaux University Hospital, France; McGovern Medical School (M.F.), University of Texas Health Science Center at Houston; Icelandic Heart Association (V.G.), Kopavogur; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; Institute of Neuroscience and Physiology (E.J., S.K., I.S., H.W., A.Z.), Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Epidemiology, Graduate School of Public Health (L.H.K.), and Departments of Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Laboratory of Epidemiology and Population Sciences (L.L., O.M.), National Institute on Aging, Bethesda, MD; Institute of Health and Society (F.E.M., B.C.M.S.), Newcastle University, Newcastle upon Tyne, UK; MIND Center (T.H.M.), University of Mississippi Medical Center, Jackson; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health, Melbourne, Australia; Kaiser Permanente Washington Health Research Institute (B.M.P.), Seattle; and The Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX.

Objective: To determine changes in the incidence of dementia between 1988 and 2015.

Methods: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex.

Results: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%]).

Conclusion: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations.
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http://dx.doi.org/10.1212/WNL.0000000000010022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455342PMC
August 2020

Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

PLoS Med 2020 06 12;17(6):e1003102. Epub 2020 Jun 12.

MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.

Background: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D).

Methods And Findings: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors.

Conclusions: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.
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http://dx.doi.org/10.1371/journal.pmed.1003102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292352PMC
June 2020
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