Genetic Predisposition for White Matter Hyperintensities and Risk of Mild Cognitive Impairment and Alzheimer's Disease: Results from the HELIAD Study.

The present study investigated the association of genetic predisposition for white matter hyperintensities (WMHs) with incident amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD), as well as whether such an association was influenced by age, sex, and cognitive reserve. Overall, 537 individuals without aMCI or dementia at baseline were included. Among them, 62 individuals developed aMCI/AD at follow up. Genetic propensity to WMH was estimated using a polygenic risk score for WMHs (PRS WMH). The association of PRS WMH with aMCI/AD incidence was examined using COX models. A higher PRS WMH was associated with a 47.2% higher aMCI/AD incidence (p = 0.015) in the fully adjusted model. Subgroup analyses showed significant results in the older age group, in which individuals with a higher genetic predisposition for WMHs had a 3.4-fold higher risk for developing aMCI/AD at follow up (p < 0.001), as well as in the lower cognitive reserve (CR, proxied by education years) group, in which individuals with a higher genetic predisposition for WMHs had an over 2-fold higher risk (p = 0.013). Genetic predisposition for WMHs was associated with aMCI/AD incidence, particularly in the group of participants with a low CR. Thus, CR might be a modifier in the relationship between genetic predisposition for WMHs and incident aMCI/AD.

Eating Frequency, Timing, and Duration in Relation to Cognitive Performance and Alzheimer Disease Biomarkers in Adults.

BACKGROUND: The potential association between temporal dimensions of eating and cognition/cognitive declines has been poorly investigated so far. OBJECTIVES: The aim of this study was to examine relationships among eating frequency, timing and time window, and cognitive performance and novel Alzheimer disease (AD) biomarkers in cognitively healthy and mildly cognitively impaired middle-aged and older adults. METHODS: Cross-sectional data were derived from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) cohort study, including people aged 40 y or older who have a positive family history of cognitive disorder or cognition-related concerns. Cognitive performance was assessed by a battery of neuropsychological tests. Amyloid ß (Αß42), a biomarker of AD-related pathology, was measured in cerebrospinal fluid. Eating frequency, timing, and the eating time window between the first and the last meal were estimated using time-related information recorded in four 24-h recalls. RESULTS: Study participants had, on average, 5.3 ± 1.2 eating episodes per day, consumed at 8:20 ± 1.3 and 21:14 ± 1.3 h their first and their last eating episode, respectively, while their eating time window was 12.9 ± 1.6 h. Eating frequency, but not eating time window, was positively associated with global cognition, executive and language performance even after controlling for age, sex, education, BMI, and Mediterranean diet. Increasing eating frequency by 1 eating episode per day was associated with 0.169 higher global z-score. Furthermore, compared with ≤4, having 5-6 or >6 eating episodes per day was associated with better global and memory z-scores. Time of last eating episode was also positively associated with language performance. No associations were detected among eating frequency, timing and window, and AD pathology. CONCLUSIONS: An eating pattern characterized by less frequent eating and/or by earlier times is present in individuals with worse cognitive performance. Our results shed light on the relevance of temporal eating patterns as potential early markers of behavioral or metabolic changes related to AD pathology.

Development of robust normative data for the neuropsychological assessment of Greek older adults.

OBJECTIVE: Normative data for older adults may be tainted by inadvertent inclusion of undiagnosed individuals at the very early stage of a neurodegenerative process. To avoid this pitfall, we developed norms for a cohort of older adults without MCI/dementia at 3-year follow-up. METHODS: A randomly selected sample of 1041 community-dwelling individuals (age ≥ 65) received a full neurological and neuropsychological examination on two occasions [mean interval = 3.1 (SD = 0.9) years]. RESULTS: Of these, 492 participants (Group 1; 65-87 years old) were without dementia on both evaluations (CDR=0 and MMSE ≥ 26); their baseline data were used for norms development. Group 2 (n = 202) met the aforementioned criteria only at baseline, but not at follow-up. Multiple linear regressions included demographic predictors for regression-based normative formulae and raw test scores as dependent variables for each test variable separately. Standardized scaled scores and stratified discrete norms were also calculated. Group 2 performed worse than Group 1 on most tests (p-values < .001-.021). Education was associated with all test scores, age with most, and sex effects were consistent with the literature. CONCLUSIONS: We provide a model for developing sound normative data for widely used neuropsychological tests among older adults, untainted by potential early, undiagnosed cognitive impairment, reporting regression-based, scaled, and discrete norms for use in clinical settings to identify cognitive decline in older adults. Additionally, our co-norming of a variety of tests may enable intra-individual comparisons for diagnostic purposes. The present work addresses the challenge of developing robust normative data for neuropsychological tests in older adults.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Depressive symptoms in the entire spectrum of cognitive ageing in Greece: evidence from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD).

OBJECTIVES: To study (i) the prevalence of mild and moderate-to-severe depressive symptoms in the entire spectrum of cognitive ageing in Greece and (ii) the relationship between these symptoms and demographic and clinical data. METHODS: The study was based on the randomly selected cohort of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Depressive symptoms were assessed with the 15-item version of the Geriatric Depression Scale. Participants also received a comprehensive neuropsychological assessment, while the clinical diagnoses of dementia and mild cognitive impairment were established according to international diagnostic criteria. Statistical analyses relied on comparison tests and a logistic (proportional odds) ordinal regression model. RESULTS: Depressive symptoms were detected in 19.5% of the 1936 study participants, while 11.3% of both people with MCI and dementia had moderate-to-severe depressive symptoms. The regression model revealed that older adults with more severe depressive symptoms were more likely female, cognitively impaired, less educated, were treated with psychotropic medication and lived in Attica versus Thessaly. CONCLUSIONS: Since depressive symptoms were detected in almost one in five older adults, healthcare professionals in Greece should safeguard the timely detection and effective treatment of such symptoms and the post-diagnostic care of older adults with depression.

Depressive symptoms are present in approximately 20% of older adults.More than 10% of older individuals with dementia or mild cognitive impairment report moderate-to-severe depressive symptoms.Female sex, lower education, lower cognitive performance, living in urban areas and treatment with psychotropic medication pertain to more severe depressive symptoms in ageing.Timely detection and effective treatment of depressive symptoms are crucial in the clinical practice of the care of older adults.Further research is needed in order to elucidate the complex relationship between depressive symptoms and cognitive impairment in ageing.

Dietary Intake, Diet Diversity, and Weight Status of Children With Food Allergy.

BACKGROUND: Adoption of allergen avoidance diets may increase the risk of nutritional deficiencies and affect growth in children with food allergy (FA). How these dietary restrictions have an impact on diet diversity, a health-promoting eating behavior, remains unclear. OBJECTIVE: To evaluate diet diversity, dietary intake, and weight status of children with FA. DESIGN: Observational study. PARTICIPANTS/SETTING: One hundred children with immunoglobulin E (IgE)-mediated milk, egg, or nut FA or multiple FAs and 60 children with perennial respiratory allergies (RA) matched as controls, aged 3 to 18 years, were consecutively recruited into the study. MAIN OUTCOME MEASURES: Dietary intake and diet diversity (number of different foods consumed/day) were assessed through 4 24-hour recalls. Weight status (underweight, healthy weight, overweight, or obesity) was also evaluated. STATISTICAL ANALYSES PERFORMED: Chi-squared test and 2-sample independent t test were used to test differences between groups. Adjustment for sex, age, and energy intake was made using linear regression. RESULTS: The percentage of underweight was higher in children with FA (19.6%) compared with children in the control group (5.1%). Children with FA compared with children in the control group consumed more servings of meat (1.7, 95% CI, 1.6, 1.9 vs. 1.5, 95% CI, 1.3, 1.7 servings/day [Padj = 0.031]). No difference was observed in the diet diversity between the 2 groups (11-12 different foods/day). Within the FA group, children with allergy to milk proteins had lower energy intake from protein, lower intake of calcium, lower consumption of commercially prepared sweets, and higher consumption of eggs, compared with children with nut or egg allergy, but no difference in diet diversity was observed. CONCLUSIONS: Diet diversity did not differ between children with FA and children with no FA, despite some differences in the intake from specific food groups. However, the higher percentage of underweight in children with FA suggests the need for targeted nutrition intervention as early as possible after FA diagnosis.

Critical menarche age for late-life dementia and the role of education and socioeconomic status.

Estrogen exposure during menstrual years has been associated with late-life neuroprotection. We explored the presence of an age-sensitive menarche window for cognition in old age and the impact of socioeconomic status and education. We compared neuropsychological performance of 1082 older women [MeanAGE = 72.69 (5.48)] with menarche in childhood, early-, mid-, and late-adolescence and dementia prevalence, severity, and type, including the effects of education and socioeconomic status. Adjusting for covariates, menarche at 11-14 years of age was associated with better memory, executive and global cognitive functioning in old age, and stronger positive effects of education and socioeconomic status on cognition than those with menarche at 15-17 years. We found a critical age window for the neuroprotective effects of estrogens during early adolescence, putting women with later menarche at higher risk for cognitive decline. Effects of socioeconomic status and education in adulthood should be a focus of future research.

Longitudinal Cognitive Trajectories in Older Adults with Restless Legs Syndrome or Willis-Ekbom Disease.

Background: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) has occasionally but not consistently been associated with cognitive and most notably language and executive impairment. The present study was conducted to investigate the cognitive trajectories of older individuals with RLS/WED. Methods: Participants were drawn from the randomly selected, older (>64 years), population-based HELIAD cohort. Individuals without dementia and with available neuropsychological evaluations at baseline and follow-up were considered for potential eligibility. A comprehensive assessment examining five principal components of cognition (memory, visuo-spatial ability, attention, executive function, and language) was administered to the participants. Generalized estimating equation analyses were used to examine the unadjusted and adjusted (for critical factors and covariates) effects of RLS/WED on cognition over time. Results: A total of 1003 predominantly female (59.5%), older (72.9 ± 4.9 years) participants with follow-up evaluations after a mean of 3.09 ± 0.85 years and without dementia at baseline and follow-up were included in the present study. Among them, 81 were diagnosed with RLS/WED at baseline. Global cognition, memory, attention, and executive and visuo-perceptual skills did not differ between those with and without RLS/WED. However, the RLS/WED group performed worse on language at baseline by a standard deviation of 0.249, while demonstrating a mitigated language decline over time, by a standard deviation of 0.063. The unadjusted models yielded similar results. Conclusions: Our findings were indicative of a baseline language disadvantage among older individuals with RLS/WED, but the initial discrepancy tends to dissolve over time.

High Adherence to the Mediterranean Dietary Pattern Is Inversely Associated with Systemic Inflammation in Older but Not in Younger Brazilian Adults.

The Mediterranean dietary pattern (MPD) has shown promise in preventing low-grade systemic inflammation (LGSI). This study tested if a high adherence to the MDP by younger and older Brazilian adults is associated with lower LGSI and investigated which Mediterranean food components may contribute to these associations. We performed a secondary study on 2015 ISA-Nutrition (290 younger adults (20-59 years old) and 293 older adults (≥60 years old)), a cross-sectional population-based study in São Paulo, SP, Brazil. The adherence to the MDP was assessed using the Mediterranean Diet Score (MedDietScore), obtained from two non-consecutive 24 h dietary recalls (24HDRs). The LGSI score (from plasma CRP, TNF-α, and adiponectin) identified the inflammatory status. Linear regression models assessed the association between LGSI and the MedDietScore. In older adults only, a high adherence to the MDP signified an 11.5% lower LGSI score. Older adults, classified with high adherence to the MDP, differed by consuming lower meat intake and full-fat dairy. Between older adults, the intake of vegetables and olive oil was inversely associated with the levels of LGSI. Thus, among older adults, the intake of some specific Mediterranean food determined high adherence to the MDP and was associated with decreased LGSI.

Walking time and genetic predisposition for Alzheimer's disease: Results from the HELIAD study.

Objective: Our study aimed to explore whether physical condition might affect the association between genetic predisposition for Alzheimer's Disease (AD) and AD incidence. Methods: The sample of participants consisted of 561 community-dwelling adults over 64 years old, without baseline dementia (508 cognitively normal and 53 with mild cognitive impairment), deriving from the HELIAD, an ongoing longitudinal study with follow-up evaluations every 3 years. Physical condition was assessed at baseline through walking time (WT), while a Polygenic Risk Score for late onset AD (PRS-AD) was used to estimate genetic predisposition. The association between WT and PRS-AD with AD incidence was evaluated with Cox proportional hazard models adjusted for age, sex, education years, global cognition score and APOE ε-4 genotype. Then, the association between WT and AD incidence was investigated after stratifying participants by low and high PRS-AD. Finally, we examined the association between PRS-AD and AD incidence after stratifying participants by WT. Results: Both WT and PRS-AD were connected with increased AD incidence (p < 0.05), after adjustments. In stratified analyses, in the slow WT group participants with a greater genetic risk had a 2.5-fold higher risk of developing AD compared to participants with lower genetic risk (p = 0.047). No association was observed in the fast WT group or when participants were stratified based on PRS-AD. Conclusions: Genetic predisposition for AD is more closely related to AD incidence in the group of older adults with slow WT. Hence, physical condition might be a modifier in the relationship of genetic predisposition with AD incidence.

Cerebral Amyloidosis in Individuals with Subjective Cognitive Decline: From Genetic Predisposition to Actual Cerebrospinal Fluid Measurements.

The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer's Disease (AD), amyloid-beta 42 (Aß42) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) individuals were included in our analyses. Among the participants, 107 had available results regarding cerebrospinal fluid (CSF) Aß42 and Tau, while 742 had available genetic data to construct polygenic risk scores (PRSs) reflecting their genetic predisposition for CSF Aß42 and plasma total Tau levels. The associations between AD biomarkers and SCD were tested using logistic regression models adjusted for possible confounders such as age, sex, education, depression, and baseline cognitive test scores. Abnormal values of CSF Aß42 were related to 2.5-fold higher odds of SCD, while higher polygenic loading for Aß42 was associated with 1.6-fold higher odds of SCD. CSF Tau, as well as polygenic loading for total Tau, were not associated with SCD. Thus, only cerebral amyloidosis appears to be related to SCD status, either in the form of polygenic risk or actual CSF measurements. The temporal sequence of amyloidosis being followed by tauopathy may partially explain our findings.

Evaluating the influence of ultra-processed food intake on associations between dietary indices with systemic inflammation in adulthood and old ages.

BACKGROUND & AIMS: Low-grade systemic inflammation (LGSI) is critical to developing many chronic diseases. In turn, it has been shown that the diet can modulate favorably or unfavorably the inflammatory status. Thus, evaluating the diet from appropriate approaches is fundamental; to do so, there are different proposals for dietary indexes. We aimed to: (i) investigate the association between three well-known dietary indexes and LGSI biomarkers; (ii) test these associations individually or in combination with an indicator of ultra-processed foods (UFPs) intake. (iii) as an additional aim, hypothesizing that all the indexes should be capable of identifying the inflammatory potential of diet, we tested the hypothesis that these indexes agree and correlate with each other. METHODS: Cross-sectional population-based data of adults and older persons (n = 583). Dietary data were obtained through two non-consecutive 24-h dietary recalls (24HDR) and calculated for Dietary Inflammatory Index (DII), Mediterranean-Style Dietary Pattern Score (MSDPS); Brazilian Healthy Eating Index - Revised (BHEI-R) and energy ingested from UPFs (UPFs ratio). An LGSI score was created from some plasma inflammatory biomarkers [C-Reactive Protein (CRP), tumor necrosis factor-alpha (TNF-α), and adiponectin]. Logistic and linear regression models tested the associations between dietary indexes and LGSI score. RESULTS: The MSDPS and DII were significantly associated with our inflammatory score, but the BHEI-R did not. Including UPFs in regression models did not increase the strength of these associations. CONCLUSIONS: From the three scores, the dietary inflammatory index and the Mediterranean-style dietary pattern score (MSDPS) were the ones that showed significant association with the inflammatory biomarker. The combination of the indexes with a ratio of UPF intake did not increase the significance of our analyses. The best agreement between the indexes was found between MSDPS and UPFs ratio; the only pair of indexes considered concordant and correlated was the BHEI-R and DII.

Associations between fruit and vegetable intakes and incident depression in middle-aged and older adults from 10 diverse international longitudinal cohorts.

BACKGROUND: Emerging observational evidence supports a role for higher fruit and vegetable intake in protecting against the development of depression. However, there is a scarcity of research in older adults or in low- to middle-income countries (LMICs). METHODS: Participants were 7801 community-based adults (mean age 68.6 ± 8.0 years, 55.8 % female) without depression, from 10 diverse cohorts, including four cohorts from LMICs. Fruit and vegetable intake was self-reported via comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated measures, and depression defined applying validated cut-offs. The associations between baseline fruit and vegetable intakes and incident depression over a follow-up period of three to nine years were examined using Cox regression. Analyses were performed by cohort with results meta-analysed. RESULTS: There were 1630 cases of incident depression (21 % of participants) over 40,258 person-years of follow-up. Higher intake of fruit was associated with a lower risk of incident depression (HR 0.87, 95%CI [0.77, 0.99], I2 = 4 %). No association was found between vegetable intake and incident depression (HR 0.93, 95%CI [0.84, 1.04], I2 = 0 %). LIMITATIONS: Diverse measures used across the different cohorts and the modest sample size of our study compared with prior studies may have prevented an association being detected for vegetable intake. CONCLUSIONS: Our study supports a role for fruit, but not vegetable intake in protecting against depression. Research investigating different types of fruits and vegetables using standardised measures in larger cohorts of older adults from low- and middle-income countries is warranted.

Blood Pressure, Antihypertensive Use, and Late-Life Alzheimer and Non-Alzheimer Dementia Risk: An Individual Participant Data Meta-Analysis.

BACKGROUND AND OBJECTIVES: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies. METHODS: This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age2, sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group. RESULTS: There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship (p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk. DISCUSSION: Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.