Introduction
In animal models, refined carbohydrates (RF) worsen Alzheimer's disease (AD). However, the long‐term effects of high RF intake on the risk of dementia and AD are poorly described in ...epidemiological studies. Moreover, the interaction between RF and the apolipoprotein E ε4 allele (APOE‐ε4) is unknown. Our study investigated whether RF‐rich diets are associated with the risk of dementia and AD.
Methods
The glycemic load (GL) was quantified in 2777 elderly participants from the French Three‐City Study to estimate RF intake. Then, the associations between GL and risk of dementia and AD, and the interaction with APOE‐ε4 over a 12‐year period were assessed using proportional hazards models.
Results
After adjustment for potential confounders, high afternoon‐snack GL was associated with increased dementia and AD risk in APOE‐ε4 carriers (hazard ratio = 1.27 1.03–1.56).
Discussion
This study highlights that RF‐rich diets are a risk factor for dementia and AD in APOE‐ε4 carriers.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
OBJECTIVE:To determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability (BPV) in the preceding 4 years.
METHODS:A total ...of 6,537 participants (mean age 79 years, 62% women) in a prospective population-based cohort were followed up for incident dementia. A 4-year time lag period was created to classify drug exposure and measure blood pressure. BPV (percent coefficient of variation CV) was regressed against 9 antihypertensive drug classes (BPVreg). Cox regression models were employed to determine hazard ratios (HRs) for incident dementia thereafter according to drug class, adjusted for mean blood pressure, covariates, and BPV or BPVreg.
RESULTS:Over a median 8.4 years follow-up (interquartile range 6.7–9.0), lower dementia risk was associated with nondihydropyridine calcium channel blocker (HR 0.56; 95% confidence interval CI 0.31–1.00, p = 0.05) and loop diuretics (HR 0.45; 95% CI 0.22–0.93, p = 0.03) after adjusting for CV-BPV. Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker (HR 0.52; 95% CI 0.28–0.95, p = 0.03) and loop diuretics (HR 0.40; 95% CI 0.19–0.83, p = 0.01). All systolic BPV × antihypertensive drug interaction terms were not different from p < 0.05.
CONCLUSIONS:Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years. Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk.
Abstract
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 (a 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 nonfrail participants of the Three-City Bordeaux cohort using a 24-hour 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.
To evaluate the predictive validity and temporal stability of diagnostic criteria for mild cognitive impairment (MCI).
MCI has been proposed as a nosologic entity referring to elderly persons with ...subclinical cognitive deficits due to incipient dementia. Classification criteria, which have been derived from small, selected clinical groups, are currently disputed, and have not yet been assessed within the general population.
Subjects meeting current criteria for MCI and also age-associated cognitive decline (AACD-a similar concept that is assumed to be related to normal cognitive aging processes rather than incipient dementia) were identified within each of three waves of a longitudinal population study, which included a standardized neurologic examination.
In the general population, the prevalence of MCI was estimated to be 3.2% and AACD 19.3%. MCI was a poor predictor of dementia within a 3-year period, with an 11.1% conversion rate. Subjects with MCI also constituted an unstable group, with almost all subjects changing category each year. Discriminant function analysis failed to isolate a homogeneous clinical group. Subjects classified as AACD, contrary to the theoretical assumptions underlying the disorder, represented a more stable group, with a 28.6% conversion rate to dementia over 3 years (relative risk = 21.2).
MCI criteria perform poorly when applied to a representative population sample. The authors propose modifications to current diagnostic criteria to increase their capacity to detect incipient dementia.
Objective To estimate the percentage reduction in incidence of dementia that would be obtained if specific risk factors were eliminated.Design Prospective seven year cohort study.Setting General ...population, Montpellier, France.Participants 1433 people aged over 65 with a mean baseline age of 72.5 (SD 5.1) years.Main outcome measures Diagnosis of mild cognitive impairment or dementia established by a standardised neurological examination.Results Cox models were constructed to derive hazard ratios and determine confounding and interaction effects for potentially modifiable risk factors for dementia. Mean percentage population attributable fractions were calculated with 95% confidence intervals derived from bootstrapping for seven year incidence of mild cognitive impairment or dementia. The final model retained crystallised intelligence (population attributable fraction 18.11%, 95% confidence interval 10.91% to 25.42%), depression (10.31%, 3.66% to 17.17%), fruit and vegetable consumption (6.46%, 0.15% to 13.06%), diabetes (4.88%, 1.87% to 7.98%), and apolipoprotein E ε4 allele (7.11%, 2.44% to 11.98%).Conclusions Increasing crystallised intelligence and fruit and vegetable consumption and eliminating depression and diabetes are likely to have the biggest impact on reducing the incidence of dementia, outweighing even the effect of removing the principal known genetic risk factor. Although causal relations cannot be concluded with certainty, the study suggests priorities that may inform public health programmes.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background
Recent evidence suggests that a high refined‐carbohydrate diet is a risk factor for dementia, especially among APOE4 carriers. Thus, refined‐carbohydrate diet may modify biomarkers of ...dementia, such as amyloid‐β (Aβ) peptides according to APOE4 carrier status. Here, we focus on afternoon‐snack glycemic load (GL) because snacks are generally richer in refined carbohydrates. We investigated the relationship between plasma Aβ, afternoon‐snack GL, and APOE4 carrier status in participants with or without incident dementia.
Method
We followed 377 non‐demented participants from the Three‐City Study (Bordeaux and Montpellier center), aged over 65, with plasma Aβ peptide concentrations measured at baseline. At 2‐year (Bordeaux center) and 4‐year (Montpellier center), the participants completed a semi‐quantitative Food Frequency Questionnaire which was used to estimate GL (GL assesses both the carbohydrate quantity and quality, and reflects glycemic response). At each follow‐up (every 2‐3 years during 15 years), participants had clinical diagnosis of dementia. We used linear regressions to evaluate the associations between plasma Aβ40, Aβ42, Aβ42/Aβ40 ratio and GL, APOE4 carrier status, and the interaction GL x APOE4, among participants with or without incident dementia. Models were adjusted for center, age, sex, education level, total cholesterol, serum creatinine and adherence to the Mediterranean diet.
Result
The sample included 60.2% of women and mean age of the participants was 76.1 (± 5.2) years. During the follow‐up, 51 participants developed dementia. Among dementia‐free participants, GL tended to be associated with Aβ42/Aβ40 ratio (β = ‐0.006 SE = 0.003, P = .055) but not with Aβ40 and Aβ42 concentrations. Among incident dementia participants, the interaction GL x APOE4 was associated with plasma Aβ40 concentration (β = 54.2 SE = 25.6 pg/mL, P = .042). Regarding Aβ42, no interaction was found. Regarding Aβ42/Aβ40 ratio, GL x APOE4 was no longer significant after adjustment (β = ‐0.038 SE = 0.024 P = .124).
Conclusion
In APOE4 carriers with incident dementia, a higher afternoon‐snack GL was associated with worse plasma Aβ peptide concentrations. These results highlight that rich refined‐carbohydrate diet is a modifiable risk factor for plasma Aβ peptide concentrations and subsequent dementia risk. Experimental studies are required to explain potential mechanism involved.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Adverse childhood events may have differential effects on the brain that persist into adulthood. Findings on structural brain alterations in older adults exposed to early-life adversity are ...inconsistent notably due to heterogeneity in imaging studies, population, psychiatric comorbidities, nature of adverse events, and genetic vulnerability. This study examines whether exposure related to physical or sexual maltreatment, emotional maltreatment, and global adverse environment during childhood are associated with specific alterations in grey matter volumes and if this varies according to sex and serotonin transporter-linked promoter region (5-HTTLPR) genotype.
Structural MRI was used to acquire anatomical scans from 398 community-dwelling older adults. Quantitative regional estimates of 23 subregional volumes were derived using FreeSurfer software. Retrospective reporting of childhood adversity was collected using structured self-reported questionnaire. Analyses adjusted for age, sex, brain volume, head injury, lifetime depression and anxiety disorder, psychiatric medication, and cardiovascular ischemic pathologies.
Exposure to adverse family environment was associated with smaller volumes of several frontal, cingulate, and parietal subregions and larger amygdala in the 5-HTTLPR SS genotype participants specifically but larger volumes of caudate, putamen, pallidum, and nucleus accumbens in the SL genotype participants. Highly significant differences were found with excessive sharing of parent problems with children, associated with larger grey-matter volumes in the thalamus and several frontal and parietal regions in 5-HTTLPR SL male participants specifically.
Early-life adversity is associated with grey-matter volume alterations in older adults and this varies according to the type of adversity experienced, sex, and serotonergic genetic vulnerability; 5-HTTLPR SS participants appearing most vulnerable and SL individuals most resilient.
•Early adverse events are associated with brain structural alterations in later life.•Their effects differ according to type of adversity, gender, and 5-HTTLPR genotype.•5-HTTLPR SS individuals appear most vulnerable and SL individuals most resilient.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective To assess the potential of anticholinergic drugs as a cause of non-degenerative mild cognitive impairment in elderly people. Design Longitudinal cohort study. Setting 63 randomly selected ...general practices in the Montpellier region of southern France. Participants 372 people aged > 60 years without dementia at recruitment. Main outcome measures Anticholinergic burden from drug use, cognitive examination, and neurological assessment. Results 9.2% of subjects continuously used anticholinergic drugs during the year before cognitive assessment. Compared with non-users, they had poorer performance on reaction time, attention, delayed non-verbal memory, narrative recall, visuospatial construction, and language tasks but not on tasks of reasoning, immediate and delayed recall of wordlists, and implicit memory. Eighty per cent of the continuous users were classified as having mild cognitive impairment compared with 35% of non-users, and anticholinergic drug use was a strong predictor of mild cognitive impairment (odds ratio 5.12, P = 0.001). No difference was found between users and non-users in risk of developing dementia at follow-up after eight years. Conclusions Elderly people taking anticholinergic drugs had significant deficits in cognitive functioning and were highly likely to be classified as mildly cognitively impaired, although not at increased risk for dementia. Doctors should assess current use of anticholinergic drugs in elderly people with mild cognitive impairment before considering administration of acetylcholinesterase inhibitors.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background: Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive health, and this could be related to the effect of air pollution on ...vascular health. Objective: We aim to evaluate the association between air pollution exposure and a magnetic resonance imaging (MRI) marker of cerebral vascular burden, white matter hyperintensities (WMH). Methods: This cross-sectional analysis used data from the French Three-City Montpellier study. Randomly selected participants 65-80 years of age underwent an MRI examination to estimate their total and regional cerebral WMH volumes. Exposure to fine particulate matter (PM.sub.2.5), nitrogen dioxide (NO.sub.2), and black carbon (BC) at the participants' residential address during the 5 years before the MRI examination was estimated with land use regression models. Multinomial and binomial logistic regression assessed the associations between exposure to each of the three pollutants and categories of total and lobar WMH volumes. Results: Participants' (n = 582) median age at MRI was 70.7 years interquartile range (IQR): 6.1, and 52% (n = 300) were women. Median exposure to air pollution over the 5 years before MRI acquisition was 24.3 (IQR: 1.7) microg/m.sup.3 for PM.sub.2.5, 48.9 (14.6) microg/m.sup.3 for NO.sub.2, and 2.66 (0.60) 10.sup.-5/m for BC. We found no significant association between exposure to the three air pollutants and total WMH volume. We found that PM.sub.2.5 exposure was significantly associated with higher risk of temporal lobe WMH burden odds ratio (OR) for an IQR increase = 1.82 (95% confidence interval: 1.41, 2.36) for the second volume tercile, 2.04 (1.59, 2.61) for the third volume tercile, reference: first volume tercile. Associations for other regional WMH volumes were inconsistent. Conclusion: In this population-based study in older adults, PM.sub.2.5 exposure was associated with increased risk of high WMH volume in the temporal lobe, strengthening the evidence on PM.sub.2.5 adverse effect on the brain. Further studies looking at different markers of cerebrovascular damage are still needed to document the potential vascular effects of air pollution.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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