IMPORTANCE: To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or Alzheimer disease (AD) dementia, markers of early detection are essential. Olfactory impairment may be ...an important clinical marker and predictor of these conditions and may help identify persons at increased risk. OBJECTIVE: To examine associations of impaired olfaction with incident MCI subtypes and progression from MCI subtypes to AD dementia. DESIGN, SETTING, AND PARTICIPANTS: Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging between 2004 and 2010 were clinically evaluated at baseline and every 15 months through 2014. Participants (N = 1630) were classified as having normal cognition, MCI (amnestic MCI aMCI and nonamnestic MCI naMCI), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. MAIN OUTCOMES AND MEASURES: Mild cognitive impairment, AD dementia, and longitudinal change in cognitive performance measures. RESULTS: Of the 1630 participants who were cognitively normal at the time of the smell test, 33 died before follow-up and 167 were lost to follow-up. Among the 1430 cognitively normal participants included, the mean (SD) age was 79.5 (5.3) years, 49.4% were men, the mean duration of education was 14.3 years, and 25.4% were APOE ε4 carriers. Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by a decrease in the number of correct responses in B-SIT score, and an increased risk of aMCI. Compared with the upper B-SIT quartile (quartile Q 4, best scores), hazard ratios (HRs) (95% CI) were 1.12 (0.65-1.92) for Q3 (P = .68); 1.95 (1.25-3.03) for Q2 (P = .003); and 2.18 (1.36-3.51) for Q1 (P = .001) (worst scores; P for trend <.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD dementia, with a significant dose-response with worsening B-SIT quartiles. Compared with Q4, HR (95% CI) estimates were 3.02 (1.06-8.57) for Q3 (P = .04); 3.63 (1.19-11.10) for Q2 (P = .02); and 5.20 (1.90-14.20) for Q1 (P = .001). After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10 95% CI, 1.04-1.16; P < .001) and improved the model concordance. CONCLUSIONS AND RELEVANCE: Olfactory impairment is associated with incident aMCI and progression from aMCI to AD dementia. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress.
Purpose
A growing body of evidence links poor maternal mental health with negative outcomes on early child development. We examined the effect of antenatal and postnatal maternal mental health on ...infant neurodevelopment at age 18 months in a population-based mother–child cohort (Rhea Study) in Crete, Greece.
Methods
Self-reported measures of maternal depression (EPDS), trait anxiety (STAI-Trait) and personality traits (EPQ-R) were assessed in a sample of women during pregnancy and at 8 weeks postpartum (
n
= 223). An additional sample of 247 mothers also completed the EPDS scale at 8 weeks postpartum (
n
= 470). Neurodevelopment at 18 months was assessed with the use of Bayley Scales of Infant and Toddler Development (3rd edition).
Results
Multivariable linear regression models adjusted for confounders revealed that antenatal depressive symptoms (EPDS ≥ 13) were associated with decrease in cognitive development independently of postnatal depression. High trait anxiety and extraversion were associated with decrease and increase, respectively, in social–emotional development. Also, high trait anxiety and neuroticism had a positive effect on infants’ expressive communication. Finally, postpartum depressive symptoms (EPDS ≥ 13) were associated with decrease in cognitive and fine motor development independently of antenatal depression.
Conclusions
These findings suggest that antenatal and postnatal maternal psychological well-being has important consequences on early child neurodevelopment.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
IMPORTANCE: Brain amyloid deposition is a marker of Alzheimer disease (AD) pathology. The population-based prevalence and outcomes of amyloid positivity in a population without dementia are important ...for understanding the trajectory of amyloid positivity to clinically significant outcomes and for designing AD prevention trials. OBJECTIVE: To determine prevalence and outcomes of amyloid positivity in a population without dementia. DESIGN, SETTING, AND PARTICIPANTS: In the prospective, population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota, participants without dementia were randomly selected from the county population and were clinically and cognitively evaluated at baseline and every 15 months from August 1, 2008, to September 18, 2018. They were also invited to undergo carbon11–Pittburgh compound B positron emission tomography (PET) imaging. EXPOSURES: Amyloid positivity (defined as a standardized uptake value ratio >1.42 on PET). MAIN OUTCOMES AND MEASURES: Prevalence of amyloid positivity in the Olmsted County population without dementia and risk of progression from no cognitive impairment (ie, normal cognition for age) to incident amnestic MCI (aMCI) and from MCI or aMCI to incident AD dementia. RESULTS: Of 3894 participants, 1671 underwent PET imaging and were included in the study; 2198 did not undergo imaging, and 25 were excluded for other reasons. The mean (SD) age of participants was 71.3 (9.8) years; 892 (53.4%) were men, and 179 (10.7%) had prevalent MCI. The prevalence of amyloid positivity without cognitive impairment in the population without dementia increased from 2.7% (95% CI, 0.5% to 4.9%) in persons aged 50 to 59 years to 41.3% (95% CI, 33.4% to 49.2%) in those aged 80 to 89 years at baseline. Prevalence of amyloid-positive MCI in the population without dementia increased from 0% in persons aged 50 to 59 years to 16.4% (95% CI, 10.3% to 22.5%) in those aged 80 to 89 years. The incident aMCI risk increased more than 2-fold in participants without cognitive impairment who were amyloid positive vs those who were amyloid negative (hazard ratio HR, 2.26; 95% CI, 1.52 to 3.35; P < .001). The risk of AD dementia was 1.86 (95% CI, 0.89 to 3.88; P = .10) for amyloid-positive participants with MCI vs amyloid-negative participants with MCI, 1.63 (95% CI, 0.78 to 3.41; P = .20) for participants with aMCI who were amyloid positive vs amyloid negative, and 2.56 (95% CI, 1.35 to 4.88; P = .004) for amyloid-positive participants who were either without cognitive impairment or had aMCI vs those who were amyloid negative. Global cognitive and memory domain z scores declined significantly in amyloid-positive individuals during follow-up. The mean (SD) follow-up time from baseline was 3.7 (1.9) years to incident aMCI and 3.8 (2.0) years to incident AD dementia. CONCLUSIONS AND RELEVANCE: Population-based prevalence of amyloid-positive status and progression rates of amyloid positivity provide valid information for designing AD prevention trials and assessing the public health outcomes of AD prevention and interventions.
Area deprivation index (ADI), a tool used to capture the multidimensional neighborhood socioeconomic disadvantage across populations, is highly relevant to the field of aging and Alzheimer’s disease ...and Alzheimer’s disease related dementias (AD/ADRD). ADI is specifically relevant in the context of resilience, a broad term used to explain why some older adults have better cognitive outcomes than others. The goal of this mini-review is three-fold: (1) to summarize the current literature on ADI and its link to cognitive impairment outcomes; (2) suggest possible mechanisms through which ADI may have an impact on AD/ADRD outcomes, and (3) discuss important considerations when studying relations between ADI and cognitive as well as brain health. Though difficult to separate both the upstream factors that emerge from high (worse) ADI and all the mechanisms at play, ADI is an attractive proxy of resilience that captures multifactorial contributors to the risk of dementia. In addition, a life-course approach to studying ADI may allow us to capture resilience, which is a process developed over the lifespan. It might be easier to build, preserve or improve resilience in an environment that facilitates instead of hindering physical, social, and cognitively beneficial activities. Neighborhood disadvantage can adversely impact cognitive impairment risk but be at the same time a modifiable risk factor, amenable to policy changes that can affect communities.
Treatment options for Alzheimer disease (AD) are limited and have focused mainly on symptomatic therapy and improving quality of life. Recently, lecanemab, an anti-β-amyloid monoclonal antibody ...(mAb), received accelerated approval by the US Food and Drug Administration for treatment in the early stages of biomarker-confirmed symptomatic AD. An additional anti-β-amyloid mAb, aducanumab, was approved in 2021, and more will potentially become available in the near future. Research on the applicability and generalizability of the anti-β-amyloid mAb eligibility criteria on adults with biomarkers available in the general population has been lacking. The study's primary aim was to apply the clinical trial eligibility criteria for lecanemab treatment to participants with early AD of the population-based Mayo Clinic Study of Aging (MCSA) and assess the generalizability of anti-amyloid treatment. The secondary aim of this study was to apply the clinical trial eligibility criteria for aducanumab treatment in MCSA participants.
This cross-sectional study aimed to apply the clinical trial eligibility criteria for lecanemab and aducanumab treatment to participants with early AD of the population-based MCSA and assess the generalizability of anti-amyloid treatment.
Two hundred thirty-seven MCSA participants (mean age SD 80.9 6.3 years, 54.9% male, and 97.5% White) with mild cognitive impairment (MCI) or mild dementia and increased brain amyloid burden by PiB PET comprised the study sample. Lecanemab trial's inclusion criteria reduced the study sample to 112 (47.3% of 237) participants. The trial's exclusion criteria further narrowed the number of potentially eligible participants to 19 (overall 8% of 237). Modifying the eligibility criteria to include all participants with MCI (instead of applying additional cognitive criteria) resulted in 17.4% of participants with MCI being eligible for lecanemab treatment. One hundred four participants (43.9% of 237) fulfilled the aducanumab clinical trial's inclusion criteria. The aducanumab trial's exclusion criteria further reduced the number of available participants, narrowing those eligible to 12 (5.1% of 237). Common exclusions were related to other chronic conditions and neuroimaging findings.
Findings estimate the limited eligibility in typical older adults with cognitive impairment for anti-β-amyloid mAbs.
Objective The purpose of this study was to investigate the association of trimester-specific gestational weight gain with offspring fetal growth, obesity risk, and cardiometabolic health outcomes ...from birth to 4 years of age. Study Design We conducted the present study with 977 mother-child pairs of the pregnancy cohort “Rhea” study in Crete, Greece. We measured birthweight, body mass index from 6 months to 4 years of age, waist circumference, skinfold thickness, blood pressure, and blood levels of lipids, C-reactive protein, and adipose tissue hormones at 4 years of age. We used multiple linear and log Poisson regression models to examine the association of exposure with continuous or binary outcomes, respectively. Results Greater rate of gestational weight gain in the first trimester of pregnancy (per 200 g/wk) was associated with increased risk of overweight/obesity from 2 years (relative risk RR, 1.25; 95% confidence interval CI, 1.09–1.42) to 4 years of age (RR, 1.15; 95% CI, 1.05–1.25), but not with birth size. Each 200 g/wk of weight gain in the first trimester of pregnancy was also associated with greater risk of high waist circumference (RR, 1.13; 95% CI, 1.04–1.23), high sum of skinfold thickness (RR, 1.15; 95% CI, 1.02–1.29), and higher diastolic blood pressure at 4 years of age (β, 0.43 mm Hg; 95% CI, 0.00–0.86). Greater rate of gestational weight gain during the second and third trimesters of pregnancy (per 200 g/wk) was associated with greater risk of large-for-gestational-age neonates (RR, 1.22; 95% CI, 1.02, 1.45) and higher levels of cord blood leptin (ratio of geometric means, 1.08; 95% CI, 1.00–1.17), but not with child anthropometry at later ages. Conclusion Timing of gestational weight gain may influence childhood cardiometabolic outcomes differentially.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
IMPORTANCE: While amyloid and neurodegeneration are viewed together as Alzheimer disease pathophysiology (ADP), the factors that influence amyloid and AD-pattern neurodegeneration may be considerably ...different. Protection from these ADP factors may be important for aging without significant ADP. OBJECTIVE: To identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration in a population-based sample and to test the hypothesis that “exceptional agers” with advanced ages do not have significant ADP because they have protective factors for amyloid and neurodegeneration. DESIGN, SETTING, AND PARTICIPANTS: This cohort study conducted a prospective analysis of 942 elderly individuals (70-≥90 years) with magnetic resonance imaging and Pittsburgh compound B–positron emission tomography scans enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We operationalized “exceptional aging” without ADP by considering individuals 85 years or older to be without significant evidence of ADP. MAIN OUTCOMES AND MEASURES: We evaluated predictors including demographics, APOE, intellectual enrichment, midlife risk factors (physical inactivity, obesity, smoking, diabetes, hypertension, and dyslipidemia), and the total number of late-life cardiac and metabolic conditions. We used multivariate linear regression models to identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration. Using a subsample of the cohort 85 years of age or older, we computed Cohen d–based effect size estimations to compare the quantitative strength of each predictor variable in their contribution with exceptional aging without ADP. RESULTS: The study participants included 423 (45%) women and the average age of participants was 79.7 (5.9) years. Apart from demographics and the APOE genotype, only midlife dyslipidemia was associated with amyloid deposition. Obesity, smoking, diabetes, hypertension, and cardiac and metabolic conditions, but not intellectual enrichment, were associated with greater AD-pattern neurodegeneration. In the 85 years or older cohort, the Cohen d results showed small to moderate effects (effect sizes > 0.2) of several variables except job score and midlife hypertension in predicting exceptional aging without ADP. CONCLUSIONS AND RELEVANCE: The protective factors that influence amyloid and AD-pattern neurodegeneration are different. “Exceptional aging” without ADP may be possible with a greater number of protective factors across the lifespan but warrants further investigation.
Objectives
To determine the association between multiple chronic conditions and risk of incident mild cognitive impairment (MCI) and dementia.
Design
Prospective cohort study.
Setting
Olmsted County, ...Minnesota.
Participants
Cognitively normal individuals (N = 2,176) enrolled in the Mayo Clinic Study of Aging (MCSA).
Measurements
Participants were randomly selected from the community, evaluated by a physician, and underwent neuropsychometric testing at baseline and at 15‐month intervals to assess diagnoses of MCI and dementia. Information on International Classification of Diseases, Ninth Revision codes for chronic conditions in the 5 years before enrollment was electronically captured using the Rochester Epidemiology Project medical records linkage system. Multimorbidity was defined as having two or more chronic conditions, and the association between multimorbidity and MCI and dementia was examined using Cox proportional hazards models.
Results
Of 2,176 cognitively normal participants (mean age ± standard deviation 78.5 ± 5.2; 50.6% male), 1,884 (86.6%) had multimorbidity. The risk of MCI or dementia was higher in persons with multimorbidity (hazard ratio (HR) = 1.38, 95% confidence interval (CI) = 1.05–1.82) than in those with one or no chronic condition. The HR was of greater magnitude in persons with four or more conditions (HR = 1.61, 95% CI = 1.21–2.13) than in those with two or three conditions (HR = 1.03, 95% CI = 0.76–1.39) and for men with multimorbidity(HR = 1.53, 95% CI = 1.01–2.31) than for women with multimorbidity (HR = 1.20, 95% CI = 0.83–1.74), compared to those with one or no chronic condition.
Conclusion
In older adults, having multiple chronic conditions is associated with greater risk of MCI and dementia. This is consistent with the hypothesis that multiple etiologies may contribute to MCI and late‐life dementia. Preventing chronic diseases may be beneficial in delaying or preventing MCI and dementia.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Maternal pre-pregnancy obesity may increase the risk of childhood obesity but it is unknown whether other metabolic factors in early pregnancy such as lipid profile and hypertension are associated ...with offspring cardiometabolic traits.
Our objective was to investigate whether fasting lipid, glucose, and insulin levels during early pregnancy and maternal pre-pregnancy weight status, are associated with offspring adiposity measures, lipid levels and blood pressure at preschool age.
The study included 618 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. Pregnant women were recruited at the first prenatal visit (mean: 12 weeks, SD: 0.7). A subset of 348 women provided fasting serum samples for glucose and lipid measurements. Outcomes measures were body mass index, abdominal circumference, sum of skinfold thickness, and blood pressure measurements at 4 years of age. A subsample of 525 children provided non-fasting blood samples for lipid measurements.
Pre-pregnancy overweight/obesity was associated with greater risk of offspring overweight/obesity (RR: 1.83, 95%CI: 1.19, 2.81), central adiposity (RR: 1.97, 95%CI: 1.11, 3.49), and greater fat mass by 5.10 mm (95%CI: 2.49, 7.71) at 4 years of age. These associations were more pronounced in girls. An increase of 40 mg/dl in fasting serum cholesterol levels in early pregnancy was associated with greater skinfold thickness by 3.30 mm (95%CI: 1.41, 5.20) at 4 years of age after adjusting for pre-pregnancy BMI and several other confounders. An increase of 10 mmHg in diastolic blood pressure in early pregnancy was associated with increased risk of offspring overweight/obesity (RR: 1.22, 95%CI: 1.03, 1.45), and greater skinfold thickness by 1.71 mm (95% CI: 0.57, 2.86) at 4 years of age.
Metabolic dysregulation in early pregnancy may increase the risk of obesity at preschool age.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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