Gemma Ortega

Validation of the Spanish Version of the Face Name Associative Memory Exam (S-FNAME) in Cognitively Normal Older Individuals

The Face Name Associative Memory Exam (FNAME) is a paired associative memory test that has demonstrated sensitivity to amyloid burden in cognitively normal individuals, a biomarker of preclinical Alzheimers disease. Normative data adjusted for age were reported in American healthy individuals older than 57. We aimed to report the psychometric characteristics of a Spanish version of FNAME (S-FNAME) when administered to Spanish-speaking people. We sought to investigate convergent validity of S-FNAME with another memory measure and to identify which demographic characteristics might be associated with performance on S-FNAME. We administered the S-FNAME to 110 literate, cognitively normal, Spanish individuals older than 49 years from the Memory Clinic Fundació ACE. Construct validity of S-FNAME showed 2 components: face-name and face-occupation. A significant correlation between S-FNAME and Word List from the WMS-III supported convergent validity. The S-FNAME was also associated with age and gender. Thus, we provide normative data for age and gender.

Impact of Recruitment Methods in Subjective Cognitive Decline

BACKGROUND Recruitment methods can determine sample characteristics in mild cognitive impairment and Alzheimers disease dementia, but little is known about its influence in subjective cognitive decline (SCD). OBJECTIVE To determine the influence of two types of recruitment methods in the characteristics of individuals with SCD. METHODS We select and compare clinical and neuropsychological features, and frequency of APOE ɛ4 allele of 326 subjects with SCD from two cohorts: Open House Initiative (OHI) versus Memory Unit (MU). A logistic regression analysis (LRA), using gender and years of education as covariates, was used to examine the neuropsychological variables. RESULTS The OHI sample were mostly women (75.9% versus 64.5%, p < 0.05), with higher educational level (12.15 [3.71] versus 10.70 [3.80] years, p = 0.001), and more family history of dementia (138 [62.7%] versus 44 [41.5%], p < 0.001) than the MU sample. Also, the OHI sample showed better overall neuropsychological performance than the MU sample, and after a LRA, this trend continued in automatic response inhibition capacity, abstract reasoning, and recognition memory. We did not find differences in age, depression history, and/or APOE ɛ4 allele frequency. CONCLUSION SCD subjects showed different demographic and neuropsychological characteristics depending on the recruitment method, which should be taken into account in the design of research studies with this target population.

Evaluation of Candidate Genes Related to Neuronal Apoptosis in Late-Onset Alzheimer's Disease

The objective of this study was to identify genetic variation in genes encoding death receptors and signals that modulate their activity. After conducting a meta-analysis with five previous genome-wide association studies and aggregated data, the most significant signals, (TNF locus: rs2395488, rs2534672, and rs9267445; and FASLG locus: rs730278), were replicated in 1,046 cases and 372 controls. The rs2395488 and rs2534672 markers showed a modest protective effect (OR = 0.849, p = 0.49780;OR= 0.687, p = 0.11335), in contrast to rs730278 marker (OR = 1.146, p = 0.17212), which did not follow the previous effect direction; in any case it reached the significance level. Final meta-analysis, adding the replication sample, confirmed these observations. We concluded that FASLG marker is not etiologically linked to Alzheimer’s disease. However, single nucleotide polymorphisms around TNF locus require further analyses in order to explain the association between Alzheimer’s disease and human leukocyte antigen.

Social Representation of Dementia: An Analysis of 5,792 Consecutive Cases Evaluated in a Memory Clinic.

Background: Different interpretations of cognitive impairment and dementia due to differences in health structures, such as cultural differences could affect the diagnosis and treatment of the condition. it is reasonable to expect that the social and family impact of the disease and coping strategies will differ among societies. Objective: The general aim of this study is to understand the social representations of dementia, its associated practices, and the effects they imply. Methods: People diagnosed with clinical dementia and their families were assessed from 2005 to 2015 in the memory clinic of the Fundació ACE, Institut Català de Neurociències Aplicades in Barcelona, Spain. Results: 9,898 people were examined and 5,792 were diagnosed with dementia. For those with a caregiver (71%), the decision-making fell on the person with dementia in 16.2% of the cases; and for those without a caregiver, in 26.4% of the cases the family did not perceive the deficits as a disease, which led to multiple risk situations (74.6%). Conclusions: The recognition of dementia as part of aging is common among families. Consequently, risk situations may arise and diagnosis and access to treatment may be delayed. The incorporation of a social appraisal to the diagnostic process is a necessity to evaluate these situations.

Genome-wide significant risk factors on chromosome 19 and the APOE locus

The apolipoprotein E (APOE) gene on chromosome 19q13.32, was the first, and remains the strongest, genetic risk factor for Alzheimer’s disease (AD). Additional signals associated with AD have been located in chromosome 19, including ABCA7 (19p13.3) and CD33 (19q13.41). The ABCA7 gene has been replicated in most populations. However, the contribution to AD of other signals close to APOE gene remains controversial. Possible explanations for inconsistency between reports include long range linkage disequilibrium (LRLD). We analysed the contribution of ABCA7 and CD33 loci to AD risk and explore LRLD patterns across APOE region. To evaluate AD risk conferred by ABCA7 rs4147929:G>A and CD33 rs3865444:C>A, we used a large Spanish population (1796 AD cases, 2642 controls). The ABCA7 rs4147929:G>A SNP effect was nominally replicated in the Spanish cohort and reached genome-wide significance after meta-analysis (odds ratio (OR)=1.15, 95% confidence interval (95% CI)=1.12–1.19; P = 1.60 x 10-19). CD33 rs3865444:C>A was not associated with AD in the dataset. The meta-analysis was also negative (OR=0.98, 95% CI=0.93–1.04; P=0.48). After exploring LRLD patterns between APOE and CD33 in several datasets, we found significant LD (D’ >0.20; P <0.030) between APOE-Ɛ2 and CD33 rs3865444C>A in two of five datasets, suggesting the presence of a non-universal long range interaction between these loci affecting to some populations. In conclusion, we provide here evidence of genetic association of the ABCA7 locus in the Spanish population and also propose a plausible explanation for the controversy on the contribution of CD33 to AD susceptibility.

RISK KNOWLEDGE OF MCI PATIENTS IN PREDICTIVE DIAGNOSIS OF ALZHEIMER’S DEMENTIA: PRELIMINARY DATA OF A MIXED METHOD APPROACH—THE PREDADQOL STUDY

missing values imputed by last observation carried forward (LOCF). Results: Data was available for 969 patients (France 1⁄4 419; Germany 1⁄4 550) at baseline, while 668 and 404 patients had data at 18 and 36-months respectively. Greater dependence was observed at baseline for more advanced stages of disease (Fig 1). Figure 2 characterizes dependence level changes among baseline mild AD participants. At 18 months, 47.1% had no change, while 25.4%, 13.2% and 3.6%worsened by 1, 2 or 3 levels respectively. Comparable 36-month figures were 42.2% without change while activity 3 Supervision on all types of IADLs or home-bound Extensive home care services with supervision OR assisted living 4 Supervision on some BADLs Assisted living + nursing support 5 Impaired transfer OR complete incontinence Nursing home

ARE THERE DIFFERENCES IN THE OPINION OF PATIENTS WITH ALZHEIMER DISEASE AND THEIR CAREGIVERS ABOUT HAVING SUPPORT FROM A SERVICE ROBOT AT HOME

experiences. Our innovative study provided a means for individuals with dementia to express how they experienced music therapist-led group singing in a residential care home. The guiding research question was: What is the experience of music therapist-led group singing for individuals with dementia living in a residential care facility? Methods: Six male residents, diagnosed with moderate to advanced dementia and ranging in age from 78 to 92 years, participated in six 30-minute group singing sessions facilitated by a music therapist who also played the piano. Repertoire incorporated familiar folk, pop, country and hymn selections. Sources of data included observation, field notes, video recording, and individual interviews (fully recorded and transcribed), which were analyzed using an adapted observational checklist (Davidson & Fedele, 2011) and Interpretive Phenomenological Analysis (Smith & Osborn, 2003). Results: The analysis process produced six themes that described three aspects of the singers’ experience of group singing: (1) how they experienced themselves (Self as Performer, Self as Part of a Group); (2) how they experienced the music (Live Music is Special; Music is a Gift); and (3) how they experienced dementia and music (Gaps in Time, Memory and Ability; The Music Is Still There). During post-singing session interviews, participants were able to express a range of feelings (e.g., joy, pride, pleasure, relaxation), despite verbal limitations. Conclusions:Conclusions included support about the value and appropriateness of engaging individuals with dementia in research (as participants were able to contribute meaningful data) as well as, in group singing led by a music therapist. Furthermore, evidence supporting group singing as an aspect of dementia care that contributes to wellbeing (as conceptualized by the PERMA model’s five elements of positive emotions, engagement, relationships, meaning, and achievement, Seligman, 2011) was noted.

Exploring APOE genotype effects on Alzheimer's disease risk and amyloid β burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results

Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimers disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored.

THE SPANISH VERSION OF FACE-NAME ASSOCIATIVE MEMORY EXAM (S-FNAME) PERFORMANCE IS RELATED TO AMYLOID BURDEN IN SUBJECTIVE COGNITIVE DECLINE

O1-13-06 THE SPANISH VERSION OF FACE-NAME ASSOCIATIVE MEMORY EXAM (S-FNAME) PERFORMANCE IS RELATED TO AMYLOID BURDEN IN SUBJECTIVE COGNITIVE DECLINE Monserrat Alegret, Angela Sanabria, Octavio Rodriguez-Gomez, Sergi Valero, Oscar Sotolongo-Grau, Carla Abdelnour, Ana Espinosa, Gemma Ortega, Alba Perez, Anna Gailhajanet, Marta Ibarria, Susana Diego, Marina Guitart, Isabel Hernandez, Maitee RosendeRoca, Liliana Vargas, Ana Mauleon, Domingo Sanchez, Silvia Gil, Miguel Santos, Elvira Mart ın, Francisco Lome~na, Agust ın Ruiz, Lluis Tarraga, Merc e Boada, Fundaci o ACE, Barcelona Alzheimer Treatment & Research Center, Barcelona, Spain; Hospital Universitari Vall d’Hebron, Barcelona, Spain; Hospital Clinic de Barcelona, Barcelona, Spain. Contact e-mail: malegret@fundacioace.com

GENETIC DETERMINANTS OF ALZHEIMER'S DISEASE PROGRESSION: EXPLORATORY ANALYSIS OF INTERNATIONAL GENOMICS OF ALZHEIMER PROJECT (IGAP) GENETIC MARKERS IN MMSE RATE OF DECLINE AND GDS

tion with dose of the e2 in total sample including e2+ and e33 subjects. The most significant SNP was examined for gene expression of all the genes within +/500kb from the SNP. Results:Genomewide significant association (P<5x10) was identified among e2+ subjects with rs192939675, resides near the 5’ end of PPP2CB and has a minor allele frequency of 7% in this subgroup (P1⁄49.8 x10, OR1⁄42.86, 95% CI1⁄42.01-4.07) but not associated with AD among e33 subjects (P1⁄40.44). Interaction between rs192939675 and dose of the e2 was significant in the total sample (P1⁄41.4x10). Rs192939675 significantly modulates expression of PPP2CB in blood (P1⁄45.9 x10), but not of other transcripts in the region. The most significant SNP from the MAPT/KANSL1 region (rs187270294) is located in KANSL1 and is more strongly associated in e2+ (P1⁄44.5 x10) than in e33 (P1⁄40.02) subjects. We also observed significant interaction between rs187270294 and dose of the e2 in the total sample (P1⁄42.6 x10). Conclusions: We identified a novel AD gene, PPP2CB, for which the effect on AD risk is modulated by the APOE e2 allele. PPP2CB encodes the catalytic subunit (beta isozyme) of protein phosphatase 2A, which is known to dephosphorylate tau protein. Future studies are needed to confirm the novel gene association and determine its precise roles in AD pathogenesis.