Nina Gramunt

Psychometric Properties of the Memory Binding Test: Test-Retest Reliability and Convergent Validity

BACKGROUND Episodic memory testing is fundamental for the diagnosis of Alzheimers disease (AD). Although the Free and Cued Selective Reminding Test (FCSRT) is widely used for this purpose, it may not be sensitive enough for early detection of subtle decline in preclinical AD. The Memory Binding Test (MBT) intends to overcome this limitation. OBJECTIVES To analyze the test-retest reliability of the MBT and its convergent validity with the FCRST. METHODS 36 cognitively healthy participants of the ALFA Study, aged 45 to 65, were included for the test-retest study and 69 for the convergent analysis. They were visited twice in a period of 6 ± 2 weeks. Test-retest reliability was determined by the calculation of the intra-class correlation coefficient (ICC). Score differences were studied by computing the mean percentage of score variation between visits and visualized by Bland-Altman plots. Convergent validity was determined by Pearsons correlations. RESULTS ICC values in the test-retest reliability analysis of the MBT direct scores ranged from 0.64 to 0.76. Subjects showed consistent practice effects, with mean amounts of score increasing between 10% and 26%. Pearson correlation between MBT and FCSRT direct scores showed r values between 0.40 and 0.53. The FCSRT displayed ceiling effects not observed in the MBT. CONCLUSIONS The MBT shows adequate test-retest reliability and overall moderate convergent validity with the FCSRT. Unlike the FCSRT, the MBT does not have ceiling effects and it may therefore be especially useful in longitudinal studies, facilitating the measurement of subtle memory performance decline and the detection of very early AD.

The ALFA project: A research platform to identify early pathophysiological features of Alzheimer's disease

The preclinical phase of Alzheimers disease (AD) is optimal for identifying early pathophysiological events and developing prevention programs, which are shared aims of the ALFA project, including the ALFA registry and parent cohort and the nested ALFA+ cohort study.

Effect of long-term exposure to air pollution on anxiety and depression in adults: A cross-sectional study

BACKGROUND The association between exposure to air pollutants and mental disorders among adults has been suggested, although results are not consistent. OBJECTIVE To analyze the association between long-term exposure to air pollution and history of anxiety and depression disorders and of medication use (benzodiazepines and antidepressants) in adults living in Barcelona. METHODS A total of 958 adults (45-74 years old) residents in Barcelona, most of them having at least one of their parents diagnosed with dementia (86%), and participating in the ALFA (Alzheimer and Families) study, were included. We used Land Use Regression (LUR) models to estimate long-term residential exposure (period 2009-2014) to PM2.5, PM2.5 absorbance (PM2.5 abs), PM10, PM coarse, NO2 and NOx. Between 2013 and 2014 participants self-reported their history of anxiety and depression disorders and related medication use. The analysis was focused on those participants reporting outcome occurrence from 2009 onwards (until 2014). RESULTS We observed an increased odds of history of depression disorders with increasing concentrations of all air pollutants [e.g. an increased odds of depression of 2.00 (95% CI; 1.37, 2.93) for each 10μg/m3 NO2 increase]. Such associations were consistent with an increased odds of medication use in relation to higher concentrations of air pollutants [e.g. an increased odds of antidepressants use of 1.23 (1.04, 1.44) for each 20μg/m3 NOx increase]. Associations regarding anxiety disorders did not reach statistical significance. CONCLUSIONS Our study shows that increasing long-term exposure to air pollution may increase the odds of depression and the use of antidepressants and benzodiazepines. Further studies are needed to replicate our results and confirm this association.

The Memory Binding Test: Development of Two Alternate Forms into Spanish and Catalan.

BACKGROUND The Memory Binding Test (MBT) is emerging as a promising tool for the detection of subtle memory impairment suggestive of Alzheimers disease (AD). For such a test to be widely accessed and used, the availability of both alternate forms and language adaptations is required. OBJECTIVES To develop a thorough methodology for obtaining alternate forms (A and B) of the MBT in Spanish and Catalan and to assess their equivalence. METHOD According to the original development of the test, frequency was taken as the lexical variable of reference for the Spanish and Catalan adaptations. A crossed design protocol by form and language was used to compare the MBT results in a sample of 290 cognitively normal middle-aged participants. Pairwise Intraclass Correlation Coefficients (ICCs) were calculated among the six possible combinations. RESULTS The Spanish and Catalan lists of words for the MBT A and B resulting from the adaptation process as well as the original lists in English are presented. ICC indices for the comparisons between forms and languages ranged from 0.56 to 0.82. CONCLUSION The MBT A and B in Spanish and Catalan showed similar outcomes and can be considered equivalent. Moreover, the thorough methodology presented here for the transcultural adaptation and equivalence study, could serve as a model for future adaptations of the MBT and other verbal tests.

Reference Data of the Spanish Memory Binding Test in a Midlife Population from the ALFA STUDY (Alzheimer’s and Family)

BACKGROUND The Memory Binding Test (MBT) is a novel test based on the learning of two lists of words, developed to detect early memory impairment suggestive of Alzheimers disease (AD). OBJECTIVE To present and provide reference data of the Spanish MBT in a midlife population of mainly first-degree descendants of AD patients. METHODS 472 cognitively unimpaired subjects, aged 45 to 65 and participants of the ALFA STUDY, were included. Raw scores were transformed to scaled scores on which multivariate regression analysis was applied adjusting by age, gender, and education level. A standard linear regression was employed to derive the scaled score adjusted. Sociodemographic corrections were applied and an adjustment table was constructed. RESULTS Performance was heterogeneously influenced by sociodemographic factors. Age negatively influenced free recall. Education tends to have an influence in the results showing lower performance with lower education level. Women tend to outperform men in the learning of the first list and total recall. Only a few variables were unaffected by sociodemographic factors such as those related to semantic proactive interference (SPI) and to the retention of learned material. Our results point out that some vulnerability to SPI is expectable in cognitively healthy subjects. Close to 100% of the learned material was maintained across the delay interval. CONCLUSION This study contributes with reference data for the MBT providing the necessary adjustments for sociodemographic characteristics. Our data may prove to be useful for detecting asymptomatic at-risk candidates for secondary prevention studies of AD.

Long-term exposure to residential green and blue spaces and anxiety and depression in adults: A cross-sectional study

Background Although exposure to natural outdoor environments has been consistently associated with improved perceived general health, available evidence on a protective association between this exposure and specific mental health disorders such as depression and anxiety is still limited. Objective The aim of this study was to evaluate the effects of long‐term exposure to residential green and blue spaces on anxiety and depression and intake of related medication. Additionally, we aimed to explore potential mediators and effect modifiers of this association. Methods The study was based on an existing adult cohort (ALFA – Alzheimer and Families) and includes 958 adult participants from Barcelona recruited in 2013–2014. For each participant residential green and blue exposure indicators [surrounding greenness (NDVI), amount of green (land‐cover) and access to major green spaces and blue spaces] were generated for different buffers (100 m, 300 m and 500 m). Participants reported their history of doctor‐diagnosed anxiety and depressive disorders and intake of related medication. Logistic regression models were applied to assess the corresponding associations. Results Increasing surrounding greenness was associated with reduced odds of self‐reported history of benzodiazepines [e.g. Odds ratio ‐ OR (95%CI) = 0.62 (0.43, 0.89) for 1‐interquartile range (IQR) increase in NDVI in a 300 m buffer] and access to major green spaces was associated with self‐reported history of depression [OR (95%CI) = 0.18 (0.06, 0.58)]. No statistically significant associations were observed with blue spaces. Air pollution (between 0.8% and 29.6%) and noise (between 2.2% and 5.3%) mediated a proportion of the associations observed, whereas physical activity and social support played a minor role. Conclusion Our findings suggest a potential protective role of green spaces on mental health (depression and anxiety) in adults, but further studies, especially longitudinal studies, are needed to provide further evidence of these benefits and of the mediation role of exposures like air pollution and noise. HighlightsIncreasing surrounding greenness associated with reduced odds of use of benzodiazepines.Access to major green spaces was associated with self‐reported history of depression.Air pollution and noise explained a proportion of the associations observed.No associations between blue spaces and mental health outcomes were observed.The present study suggests a potential protective role of green spaces on mental health.

Alzheimer’s disease prevention: from risk factors to early intervention

Due to the progressive aging of the population, Alzheimer’s disease (AD) is becoming a healthcare burden of epidemic proportions for which there is currently no cure. Disappointing results from clinical trials performed in mild–moderate AD dementia combined with clear epidemiological evidence on AD risk factors are contributing to the development of primary prevention initiatives. In addition, the characterization of the long asymptomatic stage of AD is allowing the development of intervention studies and secondary prevention programmes on asymptomatic at-risk individuals, before substantial irreversible neuronal dysfunction and loss have occurred, an approach that emerges as highly relevant.In this manuscript, we review current strategies for AD prevention, from primary prevention strategies based on identifying risk factors and risk reduction, to secondary prevention initiatives based on the early detection of the pathophysiological hallmarks and intervention at the preclinical stage of the disease. Firstly, we summarize the evidence on several AD risk factors, which are the rationale for the establishment of primary prevention programmes as well as revising current primary prevention strategies. Secondly, we review the development of public–private partnerships for disease prevention that aim to characterize the AD continuum as well as serving as platforms for secondary prevention trials. Finally, we summarize currently ongoing clinical trials recruiting participants with preclinical AD or a higher risk for the onset of AD-related cognitive impairment.The growing body of research on the risk factors for AD and its preclinical stage is favouring the development of AD prevention programmes that, by delaying the onset of Alzheimer’s dementia for only a few years, would have a huge impact on public health.

Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project

Objectives To describe the prevalence of brain MRI incidental findings (IF) in a cohort of cognitively normal first-degree descendants of patients with Alzheimers disease (AD). Design Cross-sectional observational study. Setting All scans were obtained with a 3.0 T scanner. Scans were evaluated by a single neuroradiologist and IF recorded and categorised. The presence of white matter hyperintensities (WMH) was determined with the Fazekas scale and reported as relevant if ≥2. Participants 575 participants (45–75 years) underwent high-resolution structural brain MRI. Participants were cognitively normal and scored over the respective cut-off values in all the following neuropsychological tests: Mini-Mental State Examination (≥26), Memory Impairment Screen (≥6), Time Orientation Subtest of the Barcelona Test II (≥68), verbal semantic fluency (naming animals ≥12). Clinical Dementia Rating (CDR) had to be 0. Results 155 participants (27.0%) presented with at least one IF. Relevant WMH were present in 7.8% of the participants, and vascular abnormalities, cyst and brain volume loss in 10.7%, 3.1% and 6.9% of the study volunteers, respectively. Neoplastic brain findings were found in 2.4% of participants and within these, meningiomas were the most common (1.7%) and more frequently found in women. A positive correlation between increasing age and the presence of IF was found. Additionally, brain atrophy greater than that expected by age was significantly more prevalent in participants without a parental history of AD. Conclusions Brain MRIs of healthy middle-aged participants show a relatively high prevalence of IF even when study participants have been screened for subtle cognitive alterations. Most of our participants are first-degree descendants of patients with AD, and therefore these results are of special relevance for novel imaging studies in the context of AD prevention in cognitively healthy middle-aged participants. Trial registration number NCT02198586.

Effects of APOE-ε4 allele load on brain morphology in a cohort of middle-aged healthy individuals with enriched genetic risk for Alzheimer's disease

Apolipoprotein E (APOE)‐ε4 is the major genetic risk factor for Alzheimers disease. However, the dose‐dependent impact of this allele on brain morphology of healthy individuals remains unclear.

One-Year Reference Norms of Cognitive Change in Spanish Old Adults: Data from the NEURONORMA Sample

OBJECTIVE Serial cognitive assessments are useful for many purposes, such as monitoring cognitive decline or evaluating the result of an intervention. In order to determine if an observed change is reliable and meaningful, longitudinal reference data from non-clinical samples are needed. Since neuropsychological outcomes are affected by language and cultural background, cognitive tests should be adapted, and country-based norms collected. The lack of cross-sectional normative data for Spanish population has been partially remediated, but there is still a need of reliable change norms. This paper aims to give an initial response to this need by providing several reliable change indices (RCI) for 1-year follow-up in a Spanish sample. METHOD A longitudinal observational study was designed. A total of 122 healthy subjects over age 50 were evaluated twice (M = 369.5, SD= 10.7 days) with the NEURONORMA battery. Scores changes were analyzed, and simple discrepancy scores, standard deviation indices, RCI, and standardized regression-based scores were calculated. RESULTS Significant improvements were observed in variables related to memory, both verbal and visual, visuospatial function, and the completion time of complex problems. Reference tables for several RCI are provided for their use in clinical settings. CONCLUSIONS Our results confirm the existence of heterogeneous practice effects after 1 year, and support the recommendation of using reliable change norms to avoid misdiagnosis in repeated assessments. This study provides with initial, preliminary norms of cognitive change for its use in Spanish elders. Further studies on larger samples and different inter-visit intervals are still needed.