Carla Abdelnour - Academia.edu (original) (raw)

Papers by Carla Abdelnour

Annals of neurology, Jun 18, 2024

Proceedings of the National Academy of Sciences, Aug 28, 2023

Plasma amyloid beta levels measured with ABtest for the FACEHBI samples. (XLSX 28 kb)

Annals of clinical and translational neurology, Mar 4, 2024

Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2022

Alzheimer's disease (AD) and other dementias are a global challenge. Early diagnosis is important... more Alzheimer's disease (AD) and other dementias are a global challenge. Early diagnosis is important to manage the disease. However, there are barriers to diagnosis that differ by region. Researchers from Brazil, China, Nigeria, Spain, and Sweden have identified key barriers to AD diagnosis in their countries. In Brazil, socioeconomic inequalities and poor recognition of dementia by physicians can prevent diagnosis. In China, a very large population and lack of physician training in dementia make diagnosis problematic. In Nigeria, socioeconomic inequalities and cultural stigma can stand in the way of diagnosis. In Spain, patient hesitancy and an overloaded health-care system are barriers to diagnosis. In Sweden, inconsistent use of biomarkers is a prominent barrier to diagnosis of AD. To support diagnosis, more focus is needed on education of patients and physicians, increased use of support services, and improved access to biomarkers to accurately diagnose AD.

PLOS ONE, Jul 7, 2023

Ethical challenges of using remote monitoring technologies for clinical research: A case study of... more Ethical challenges of using remote monitoring technologies for clinical research: A case study of the role of local research ethics committees in the RADAR-AD study. PLoS ONE 18(7): e0285807.

Current Opinion in Neurology, Jun 9, 2023

Purpose of review Currently, no disease modifying therapies (DMTs) have been approved for use in ... more Purpose of review Currently, no disease modifying therapies (DMTs) have been approved for use in dementia with Lewy bodies (DLB). Clinical trials face difficulties due to the clinical and neuropathological heterogeneity of the condition with a diverse array of neuropathogenic mechanisms contributing to the clinical phenotype. The purpose of this review is to describe how recent advances in the development of biofluid biomarkers may be used in clinical trials to tackle some of these challenges. Recent findings Biomarkers are essential both to support the accurate diagnosis of DLB and to delineate the influence of coexisting pathologies. Recent advances in the development of α-synuclein seeding amplification assays (SAA) allow accurate identification of α-synuclein from the prodromal stages in DLB. Additionally, validation of plasma phosphorylated tau assays in DLB is ongoing and offers an accessible biomarker to indicate the existence of AD co-pathology. Use of biomarkers for diagnosis and group stratification in clinical trials of DLB is growing and likely to be of increasing importance in the future. Summary In vivo biomarkers can enhance patient selection in clinical trials allowing greater diagnostic accuracy, a more homogeneous trial population, and stratification by co-pathology to create subgroups most likely to derive therapeutic benefit from DMTs.

Seminars in Neurology, Mar 20, 2023

Patients with neurodegenerative movement disorders can develop cognitive impairment during the di... more Patients with neurodegenerative movement disorders can develop cognitive impairment during the disease. Cognitive symptoms have been associated with decreased quality of life, higher caregiver burden, and earlier institutionalization, and are therefore critical for physicians to understand and address. The evaluation of cognitive performance of patients with neurodegenerative movement disorders is important for providing adequate diagnosis, management, prognosis, and support patients and their caregivers. In this review, we discuss the features of the cognitive impairment profile of commonly encountered movement disorders: Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome, and Huntington's disease. In addition, we provide neurologists with practical guidance and evaluation tools for the assessment and management of these challenging patients.

Alzheimers & Dementia, Dec 1, 2020

Background: FDA has made great efforts to promote inclusion of women in clinical trials. The aim ... more Background: FDA has made great efforts to promote inclusion of women in clinical trials. The aim is to protect specific biological gender and sex issues and encourage drug developers to consider specific clinical outcomes and drug-safety profiles in terms of gender and sex. Alzheimer's disease (AD) affects predominantly women, who double men in the number of patients diagnosed with dementia. Therefore, we explored gender and sex bias in the inclusion criteria for clinical trials in AD. Here our aim was to compare main inclusion criteria for clinical trials in MCI and dementia patients in terms of sex. Method: Patients evaluated at FACE from 1996 to 2019 with CDR 0,5 to 2 evaluated from 1996 to 2019 were analyzed. Then, we used the main inclusion criteria for AD clinical trials to compare the sample in terms of sex and syndromic diagnosis. The chosen variables were age, sex, education, comorbidities, treatment and MMSE score. Logistic regression analysis was used accounting for these variables. Result: From a total sample of 20,203 MCI and dementia patients, we selected potential candidates for clinical trials with complete information regarding age, years of education, MMSE, comorbidities and treatment. After adjusting for age, years of education, comorbidities and treatment, in the dementia sample only age and years of education showed statistically significant differences. Whereas in the MCI sample: age, years of education, treatment and comorbidities showed statistically significant differences (Table 1 and 2). Conclusion: Women with MCI and dementia are less likely to participate in a clinical trial due to older age and less years of education than men. Another factor that prevent women for participating in clinical trials is their comorbidities when compared to men, whereas men are excluded due to treatment criteria more often than women.

Alzheimers & Dementia, Dec 1, 2020

Background: FDA has made great efforts to promote inclusion of women in clinical trials. The aim ... more Background: FDA has made great efforts to promote inclusion of women in clinical trials. The aim is to protect specific biological gender and sex issues and encourage drug developers to consider specific clinical outcomes and drug-safety profiles in terms of gender and sex. Alzheimer's disease (AD) affects predominantly women, who double men in the number of patients diagnosed with dementia. Therefore, we explored gender and sex bias in the inclusion criteria for clinical trials in AD. Here our aim was to compare main inclusion criteria for clinical trials in MCI and dementia patients in terms of sex. Method: Patients evaluated at FACE from 1996 to 2019 with CDR 0,5 to 2 were analysed. Then, we used the main inclusion criteria for AD clinical trials to compare the sample in terms of sex and syndromic diagnosis. The chosen variables were age, sex, education, comorbidities, treatment and MMSE score. Logistic regression analysis accounting for age, years of education, MMSE, treatment and comorbidities was used. Result: From a total sample of 20,203 MCI and dementia patients, we selected potential candidates for clinical trials with complete information regarding age, age, years of education, MMSE, comorbidities and treatment. After adjusting for age, years of education, MMSE, comorbidities and treatment, in the dementia sample only age and years of education showed statistically significant differences. Whereas in the MCI sample: age, years of education, treatment and comorbidities showed statistically significant differences (Tables 1 and 2) Conclusion: Women with MCI and dementia are less likely to participate in a clinical trial due to older age and less years of education than men. Another factor that prevent women for participating in clinical trials is their comorbidities when compared to men, whereas men are excluded due to treatment criteria more often than women.

Scientific Reports, Apr 3, 2023

Although beta-amyloid (Aβ) and phosphorylated tau remain the preferred targets for diseasemodifyi... more Although beta-amyloid (Aβ) and phosphorylated tau remain the preferred targets for diseasemodifying treatments (DMT) against Alzheimer's disease (AD), part of the pathophysiological mechanisms of cognitive impairment are related to neuroinflammation and oxidative stress. In mild cognitive impairment (MCI), a prodromal stage of AD and other neurodegenerative conditions, the joint appearance of inflammation, oxidative stress, and metabolic alterations are the common pathways of neurotoxicity and neurodegeneration. The standardized extract of Ginkgo biloba EGb 761 interferes with the pathogenic mechanisms involved in both the development of cognitive impairment due to AD and that of vascular origin. The primary objective of this study is to compare changes in the levels of blood markers of inflammation and oxidative stress after treatment with EGb 761 in a cohort of 100 patients with MCI. In addition, we aim to assess changes in these blood markers during an additional 12-month extension phase in which patients in the control group will also receive EGb 761 and patients in the active group will extend their treatment duration. Secondary objectives include comparing changes in neuropsychiatric and cognitive test scores between the baseline (v0) and 12-month visits (v2). This study is a Phase IV, single-center, randomized, open-label, parallelgroup clinical trial consisting of the 12-month follow-up of a cohort of participants with MCI [Global Deterioration Scale (GDS) = 3] and an extension with an additional 12-month follow-up. During the first 12 months, participants will be randomized into two arms: in one arm, patients will receive 1 daily tablet of EGb 761 240 mg orally (study group, n = 50), while in the other arm, patients will not receive EGb 761 and will undergo the same assessments as the treated group (control group, n = 50). After the first 12 months of the study, patients in the EGb 761-treated group will continue treatment, and patients in the control group will be offered one EGb 761 240 mg tablet per day orally. All participants will be monitored for an additional 12 months. A battery of blood markers of inflammation and oxidative stress will be quantified at v0, v1, v2, v3, and v4. The Olink Proteomics panel of inflammation markers (https:// www. olink. com/ produ cts/ infla mmati on/) will be used to evaluate 92

Oncotarget, May 15, 2018

The apolipoprotein E (APOE) gene on chromosome 19q13.32, was the first, and remains the strongest... more 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 www.oncotarget.com

Alzheimers & Dementia, Jul 1, 2016

Scientific Reports, Nov 18, 2020

To date, very few studies have been focused on the impact of the convergence of neuropsychiatric ... more To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3-2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic. Mild Cognitive Impairment (MCI) is a relevant syndromic entity characterized by early stages of cognitive decline with preserved autonomy and it is frequently associated with neurodegenerative diseases, Alzheimer's disease (AD) being the most prevalent one 1. As MCI is considered an intermediated diagnosis between normal cognition and dementia, much effort has been dedicated to the identification of those individuals with MCI with a higher vulnerability of conversion to dementia. The study of the simultaneous effect of neuropsychiatric symptoms and genes is increasing its interest in recent years 2. Considering that a susceptibility condition can be better explained by the confluence of a behavioral status and the effect of one or more genes, the main idea is to highlight the relevance of gene-behavioral interactions. To date, only two studies have looked into the interaction between NPS and APOE when determining an increased risk of the hazard of an eventual case of dementia 3,4. These studies have shown significant interactions between behavioral disturbances and APOE ε4 in predicting of incident dementia in cognitively healthy individuals or MCI patients extracted from population-based cohorts. However, nothing is known about the combined contribution of these two risk factors on the conversion to dementia in MCI patients diagnosed and followed in a Memory Clinic. The objective of the present study is to determine the effect of interaction of NPS and APOE ε4 on conversion to dementia in a large sample of MCI patients, controlling for several relevant clinical factors.

Scientific Reports, Mar 19, 2021

Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alz... more Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alzheimer's disease (AD) and other dementia types in patients diagnosed with Mild Cognitive Impairment (MCI). Our aim was to determine profiles based on the prominent NPS in MCI patients and to explore the predictive value of these profiles on conversion to specific types of dementia. A total of 2137 MCI patients monitored in a memory clinic were included in the study. Four NPS profiles emerged (classes), which were defined by preeminent symptoms: Irritability, Apathy, Anxiety/Depression and Asymptomatic. Irritability and Apathy were predictors of conversion to dementia (HR = 1.43 and 1.56, respectively). Anxiety/depression class showed no risk effect of conversion when compared to Asymptomatic class. Irritability class appeared as the most discriminant neuropsychiatric condition to identify non-AD converters (i.e., frontotemporal dementia, vascular dementia, Parkinson's disease and dementia with Lewy Bodies). The findings revealed that consistent subgroups of MCI patients could be identified among comorbid basal NPS. The preeminent NPS showed to behave differentially on conversion to dementia, beyond AD. Therefore, NPS should be used as early diagnosis facilitators, and should also guide clinicians to detect patients with different illness trajectories in the progression of MCI.

Scientific Reports, May 7, 2019

Alzheimers & Dementia, Jul 1, 2018

four to eight co-existing NPI symptoms. Disinhibition and irritability were common symptoms ident... more four to eight co-existing NPI symptoms. Disinhibition and irritability were common symptoms identified by the respondents. Frequency, severity and distress varied. From the narrative data thirteen categories were created; Communication challenges, lacking self-insight, a changed person, self-neglect, diagnosis before person, anti-social behaviour, suicidal thoughts, loss of impulse control, childlike behaviour, breeching social norms, coping and problem solving, support and unmet needs and fears for safety. The following two themes emerged; Living with a well-known stranger and Coping and overstepping social norms. Conclusions: Family members to persons with FTD found symptoms such as; apathy, disinhibition, and irritability most distressing. Coping and living alongside a changed family member with anti-social behaviour and other NPS was demanding on practical and emotional levels. The presence of NPS can threaten the safety and welfare of the person with FTD and their family in real world and on social media. Support offered should focus on the unique physical and psychological needs of the family.

Journal of Alzheimer's Disease, Jun 15, 2021

Background: Over the last decade, teleneuropsychology has increased substantially. There is a nee... more Background: Over the last decade, teleneuropsychology has increased substantially. There is a need for valid neuropsychological batteries to be administered home-to-home. Since 2006, the neuropsychological battery of Fundació ACE (NBACE) has been administered face-to-face in our clinical settings. Recently, we adapted the NBACE for teleneuropsychology use to be administered home-to-home (NBACEtn). Objective: The aims of the present study are: 1) to determine the home-to-home NBACE equivalence compared to its original face-to-face version; and 2) to examine home-to-home NBACE discriminant capacity by differentiating among cognitively healthy, mild cognitive impairment, or mild dementia subjects and comparing it with the face-to-face version. Methods: Data from 338 individuals assessed home-to-home (NBACEtn) were contrasted with 7,990 participants assessed with its face-to-face version (NBACE). Exploratory and confirmatory factorial structure, and invariance analysis of the two versions of the battery were performed. Results: Exploratory and confirmatory factor analysis supported the four-factor model (attention, memory, executive, and visuospatial/constructional functions). Configural, metric, and scalar measurement invariance was found between hometo-home and face-to-face NBACE versions. Significant differences in most of the neuropsychological variables assessed were observed between the three clinical groups in both versions of administration. No differences were found between the technological devices used by participants (computer or tablet and mobile devices). Conclusion: For the first time, invariance analysis findings were addressed by determining a teleneuropsychological battery's equivalence in comparison with its face-to-face version. This study amplifies the neuropsychological assessment's applicability using a home-to-home format, maintaining the original measure's structure, interpretability, and discriminant capacity.

Scientific Reports, Oct 17, 2019

Scientific Reports, Jun 18, 2019

Visual impairment is common in people living with dementia and regular ophthalmological exams may... more Visual impairment is common in people living with dementia and regular ophthalmological exams may improve their quality of life. We evaluated visual function in a cohort of elderly individuals and analyzed its association with their degree of cognitive impairment. participants underwent neurological and neuropsychological exams, neuro-ophthalmological assessment (visual acuity, intraocular pressure, rates of past ophthalmological pathologies, use of ocular correction, treatments and surgeries) and optical coherence tomography (OCT) scan. We analyzed differences in ophthalmological characteristics among diagnostic groups. The final sample of 1746 study participants aged ≥ 50 comprised 229 individuals with Subjective Cognitive Decline (SCD), 695 with mild cognitive impairment (MCI) and 833 with Dementia (Alzheimer disease: n = 660; vascular dementia: n = 92, Lewy body dementia: n = 34; frontotemporal dementia: n = 19 and other: n = 28). Age, gender and education were used as covariates. patients with Dementia, compared to those with sCD and MCI, presented worse visual acuity (p < 0.001), used less visual correction (p = 0.02 and p < 0.001, respectively) and fewer ophthalmological treatments (p = 0.004 and p < 0.001, respectively) and underwent fewer ocular surgeries (p = 0.009 and p < 0.001, respectively). OCT image quality worsened in parallel to cognitive decline (Dementia vs sCD: p = 0.008; Dementia vs MCI: p < 0.001). No group differences in past ophthalmological disorders or abnormal OCT findings were detected. Efforts should be made to ensure dementia patients undergo regular ophthalmological assessments to correct their visual function in order to improve their quality of life. Alzheimer's Disease (AD), the leading cause of dementia in the elderly, is a neurodegenerative condition that irreversibly impairs cognition 1. AD symptoms progressively develop over time and include memory loss, impairment of judgment, disorientation, personality changes and emotional disturbances 2. Visual abnormalities are also common in AD, leading to falls, confusion and difficulty with activities of daily living. In combination with visual hallucinations, poor vision can affect an individual's autonomy and quality of life 3. Large population studies have identified a higher prevalence of age-related visual problems among elderly people with dementia compared to the general population 4. The burden of both visual impairment and cognitive decline is expected to rise in the near future due to the increase in life expectancy 5,6 .

Annals of neurology, Jun 18, 2024

Proceedings of the National Academy of Sciences, Aug 28, 2023

Plasma amyloid beta levels measured with ABtest for the FACEHBI samples. (XLSX 28 kb)

Annals of clinical and translational neurology, Mar 4, 2024

Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2022

Alzheimer's disease (AD) and other dementias are a global challenge. Early diagnosis is important... more Alzheimer's disease (AD) and other dementias are a global challenge. Early diagnosis is important to manage the disease. However, there are barriers to diagnosis that differ by region. Researchers from Brazil, China, Nigeria, Spain, and Sweden have identified key barriers to AD diagnosis in their countries. In Brazil, socioeconomic inequalities and poor recognition of dementia by physicians can prevent diagnosis. In China, a very large population and lack of physician training in dementia make diagnosis problematic. In Nigeria, socioeconomic inequalities and cultural stigma can stand in the way of diagnosis. In Spain, patient hesitancy and an overloaded health-care system are barriers to diagnosis. In Sweden, inconsistent use of biomarkers is a prominent barrier to diagnosis of AD. To support diagnosis, more focus is needed on education of patients and physicians, increased use of support services, and improved access to biomarkers to accurately diagnose AD.

PLOS ONE, Jul 7, 2023

Ethical challenges of using remote monitoring technologies for clinical research: A case study of... more Ethical challenges of using remote monitoring technologies for clinical research: A case study of the role of local research ethics committees in the RADAR-AD study. PLoS ONE 18(7): e0285807.

Current Opinion in Neurology, Jun 9, 2023

Purpose of review Currently, no disease modifying therapies (DMTs) have been approved for use in ... more Purpose of review Currently, no disease modifying therapies (DMTs) have been approved for use in dementia with Lewy bodies (DLB). Clinical trials face difficulties due to the clinical and neuropathological heterogeneity of the condition with a diverse array of neuropathogenic mechanisms contributing to the clinical phenotype. The purpose of this review is to describe how recent advances in the development of biofluid biomarkers may be used in clinical trials to tackle some of these challenges. Recent findings Biomarkers are essential both to support the accurate diagnosis of DLB and to delineate the influence of coexisting pathologies. Recent advances in the development of α-synuclein seeding amplification assays (SAA) allow accurate identification of α-synuclein from the prodromal stages in DLB. Additionally, validation of plasma phosphorylated tau assays in DLB is ongoing and offers an accessible biomarker to indicate the existence of AD co-pathology. Use of biomarkers for diagnosis and group stratification in clinical trials of DLB is growing and likely to be of increasing importance in the future. Summary In vivo biomarkers can enhance patient selection in clinical trials allowing greater diagnostic accuracy, a more homogeneous trial population, and stratification by co-pathology to create subgroups most likely to derive therapeutic benefit from DMTs.

Seminars in Neurology, Mar 20, 2023

Patients with neurodegenerative movement disorders can develop cognitive impairment during the di... more Patients with neurodegenerative movement disorders can develop cognitive impairment during the disease. Cognitive symptoms have been associated with decreased quality of life, higher caregiver burden, and earlier institutionalization, and are therefore critical for physicians to understand and address. The evaluation of cognitive performance of patients with neurodegenerative movement disorders is important for providing adequate diagnosis, management, prognosis, and support patients and their caregivers. In this review, we discuss the features of the cognitive impairment profile of commonly encountered movement disorders: Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome, and Huntington's disease. In addition, we provide neurologists with practical guidance and evaluation tools for the assessment and management of these challenging patients.

Alzheimers & Dementia, Dec 1, 2020

Background: FDA has made great efforts to promote inclusion of women in clinical trials. The aim ... more Background: FDA has made great efforts to promote inclusion of women in clinical trials. The aim is to protect specific biological gender and sex issues and encourage drug developers to consider specific clinical outcomes and drug-safety profiles in terms of gender and sex. Alzheimer's disease (AD) affects predominantly women, who double men in the number of patients diagnosed with dementia. Therefore, we explored gender and sex bias in the inclusion criteria for clinical trials in AD. Here our aim was to compare main inclusion criteria for clinical trials in MCI and dementia patients in terms of sex. Method: Patients evaluated at FACE from 1996 to 2019 with CDR 0,5 to 2 evaluated from 1996 to 2019 were analyzed. Then, we used the main inclusion criteria for AD clinical trials to compare the sample in terms of sex and syndromic diagnosis. The chosen variables were age, sex, education, comorbidities, treatment and MMSE score. Logistic regression analysis was used accounting for these variables. Result: From a total sample of 20,203 MCI and dementia patients, we selected potential candidates for clinical trials with complete information regarding age, years of education, MMSE, comorbidities and treatment. After adjusting for age, years of education, comorbidities and treatment, in the dementia sample only age and years of education showed statistically significant differences. Whereas in the MCI sample: age, years of education, treatment and comorbidities showed statistically significant differences (Table 1 and 2). Conclusion: Women with MCI and dementia are less likely to participate in a clinical trial due to older age and less years of education than men. Another factor that prevent women for participating in clinical trials is their comorbidities when compared to men, whereas men are excluded due to treatment criteria more often than women.

Alzheimers & Dementia, Dec 1, 2020

Background: FDA has made great efforts to promote inclusion of women in clinical trials. The aim ... more Background: FDA has made great efforts to promote inclusion of women in clinical trials. The aim is to protect specific biological gender and sex issues and encourage drug developers to consider specific clinical outcomes and drug-safety profiles in terms of gender and sex. Alzheimer's disease (AD) affects predominantly women, who double men in the number of patients diagnosed with dementia. Therefore, we explored gender and sex bias in the inclusion criteria for clinical trials in AD. Here our aim was to compare main inclusion criteria for clinical trials in MCI and dementia patients in terms of sex. Method: Patients evaluated at FACE from 1996 to 2019 with CDR 0,5 to 2 were analysed. Then, we used the main inclusion criteria for AD clinical trials to compare the sample in terms of sex and syndromic diagnosis. The chosen variables were age, sex, education, comorbidities, treatment and MMSE score. Logistic regression analysis accounting for age, years of education, MMSE, treatment and comorbidities was used. Result: From a total sample of 20,203 MCI and dementia patients, we selected potential candidates for clinical trials with complete information regarding age, age, years of education, MMSE, comorbidities and treatment. After adjusting for age, years of education, MMSE, comorbidities and treatment, in the dementia sample only age and years of education showed statistically significant differences. Whereas in the MCI sample: age, years of education, treatment and comorbidities showed statistically significant differences (Tables 1 and 2) Conclusion: Women with MCI and dementia are less likely to participate in a clinical trial due to older age and less years of education than men. Another factor that prevent women for participating in clinical trials is their comorbidities when compared to men, whereas men are excluded due to treatment criteria more often than women.

Scientific Reports, Apr 3, 2023

Although beta-amyloid (Aβ) and phosphorylated tau remain the preferred targets for diseasemodifyi... more Although beta-amyloid (Aβ) and phosphorylated tau remain the preferred targets for diseasemodifying treatments (DMT) against Alzheimer's disease (AD), part of the pathophysiological mechanisms of cognitive impairment are related to neuroinflammation and oxidative stress. In mild cognitive impairment (MCI), a prodromal stage of AD and other neurodegenerative conditions, the joint appearance of inflammation, oxidative stress, and metabolic alterations are the common pathways of neurotoxicity and neurodegeneration. The standardized extract of Ginkgo biloba EGb 761 interferes with the pathogenic mechanisms involved in both the development of cognitive impairment due to AD and that of vascular origin. The primary objective of this study is to compare changes in the levels of blood markers of inflammation and oxidative stress after treatment with EGb 761 in a cohort of 100 patients with MCI. In addition, we aim to assess changes in these blood markers during an additional 12-month extension phase in which patients in the control group will also receive EGb 761 and patients in the active group will extend their treatment duration. Secondary objectives include comparing changes in neuropsychiatric and cognitive test scores between the baseline (v0) and 12-month visits (v2). This study is a Phase IV, single-center, randomized, open-label, parallelgroup clinical trial consisting of the 12-month follow-up of a cohort of participants with MCI [Global Deterioration Scale (GDS) = 3] and an extension with an additional 12-month follow-up. During the first 12 months, participants will be randomized into two arms: in one arm, patients will receive 1 daily tablet of EGb 761 240 mg orally (study group, n = 50), while in the other arm, patients will not receive EGb 761 and will undergo the same assessments as the treated group (control group, n = 50). After the first 12 months of the study, patients in the EGb 761-treated group will continue treatment, and patients in the control group will be offered one EGb 761 240 mg tablet per day orally. All participants will be monitored for an additional 12 months. A battery of blood markers of inflammation and oxidative stress will be quantified at v0, v1, v2, v3, and v4. The Olink Proteomics panel of inflammation markers (https:// www. olink. com/ produ cts/ infla mmati on/) will be used to evaluate 92

Oncotarget, May 15, 2018

The apolipoprotein E (APOE) gene on chromosome 19q13.32, was the first, and remains the strongest... more 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 www.oncotarget.com

Alzheimers & Dementia, Jul 1, 2016

Scientific Reports, Nov 18, 2020

To date, very few studies have been focused on the impact of the convergence of neuropsychiatric ... more To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3-2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic. Mild Cognitive Impairment (MCI) is a relevant syndromic entity characterized by early stages of cognitive decline with preserved autonomy and it is frequently associated with neurodegenerative diseases, Alzheimer's disease (AD) being the most prevalent one 1. As MCI is considered an intermediated diagnosis between normal cognition and dementia, much effort has been dedicated to the identification of those individuals with MCI with a higher vulnerability of conversion to dementia. The study of the simultaneous effect of neuropsychiatric symptoms and genes is increasing its interest in recent years 2. Considering that a susceptibility condition can be better explained by the confluence of a behavioral status and the effect of one or more genes, the main idea is to highlight the relevance of gene-behavioral interactions. To date, only two studies have looked into the interaction between NPS and APOE when determining an increased risk of the hazard of an eventual case of dementia 3,4. These studies have shown significant interactions between behavioral disturbances and APOE ε4 in predicting of incident dementia in cognitively healthy individuals or MCI patients extracted from population-based cohorts. However, nothing is known about the combined contribution of these two risk factors on the conversion to dementia in MCI patients diagnosed and followed in a Memory Clinic. The objective of the present study is to determine the effect of interaction of NPS and APOE ε4 on conversion to dementia in a large sample of MCI patients, controlling for several relevant clinical factors.

Scientific Reports, Mar 19, 2021

Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alz... more Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alzheimer's disease (AD) and other dementia types in patients diagnosed with Mild Cognitive Impairment (MCI). Our aim was to determine profiles based on the prominent NPS in MCI patients and to explore the predictive value of these profiles on conversion to specific types of dementia. A total of 2137 MCI patients monitored in a memory clinic were included in the study. Four NPS profiles emerged (classes), which were defined by preeminent symptoms: Irritability, Apathy, Anxiety/Depression and Asymptomatic. Irritability and Apathy were predictors of conversion to dementia (HR = 1.43 and 1.56, respectively). Anxiety/depression class showed no risk effect of conversion when compared to Asymptomatic class. Irritability class appeared as the most discriminant neuropsychiatric condition to identify non-AD converters (i.e., frontotemporal dementia, vascular dementia, Parkinson's disease and dementia with Lewy Bodies). The findings revealed that consistent subgroups of MCI patients could be identified among comorbid basal NPS. The preeminent NPS showed to behave differentially on conversion to dementia, beyond AD. Therefore, NPS should be used as early diagnosis facilitators, and should also guide clinicians to detect patients with different illness trajectories in the progression of MCI.

Scientific Reports, May 7, 2019

Alzheimers & Dementia, Jul 1, 2018

four to eight co-existing NPI symptoms. Disinhibition and irritability were common symptoms ident... more four to eight co-existing NPI symptoms. Disinhibition and irritability were common symptoms identified by the respondents. Frequency, severity and distress varied. From the narrative data thirteen categories were created; Communication challenges, lacking self-insight, a changed person, self-neglect, diagnosis before person, anti-social behaviour, suicidal thoughts, loss of impulse control, childlike behaviour, breeching social norms, coping and problem solving, support and unmet needs and fears for safety. The following two themes emerged; Living with a well-known stranger and Coping and overstepping social norms. Conclusions: Family members to persons with FTD found symptoms such as; apathy, disinhibition, and irritability most distressing. Coping and living alongside a changed family member with anti-social behaviour and other NPS was demanding on practical and emotional levels. The presence of NPS can threaten the safety and welfare of the person with FTD and their family in real world and on social media. Support offered should focus on the unique physical and psychological needs of the family.

Journal of Alzheimer's Disease, Jun 15, 2021

Background: Over the last decade, teleneuropsychology has increased substantially. There is a nee... more Background: Over the last decade, teleneuropsychology has increased substantially. There is a need for valid neuropsychological batteries to be administered home-to-home. Since 2006, the neuropsychological battery of Fundació ACE (NBACE) has been administered face-to-face in our clinical settings. Recently, we adapted the NBACE for teleneuropsychology use to be administered home-to-home (NBACEtn). Objective: The aims of the present study are: 1) to determine the home-to-home NBACE equivalence compared to its original face-to-face version; and 2) to examine home-to-home NBACE discriminant capacity by differentiating among cognitively healthy, mild cognitive impairment, or mild dementia subjects and comparing it with the face-to-face version. Methods: Data from 338 individuals assessed home-to-home (NBACEtn) were contrasted with 7,990 participants assessed with its face-to-face version (NBACE). Exploratory and confirmatory factorial structure, and invariance analysis of the two versions of the battery were performed. Results: Exploratory and confirmatory factor analysis supported the four-factor model (attention, memory, executive, and visuospatial/constructional functions). Configural, metric, and scalar measurement invariance was found between hometo-home and face-to-face NBACE versions. Significant differences in most of the neuropsychological variables assessed were observed between the three clinical groups in both versions of administration. No differences were found between the technological devices used by participants (computer or tablet and mobile devices). Conclusion: For the first time, invariance analysis findings were addressed by determining a teleneuropsychological battery's equivalence in comparison with its face-to-face version. This study amplifies the neuropsychological assessment's applicability using a home-to-home format, maintaining the original measure's structure, interpretability, and discriminant capacity.

Scientific Reports, Oct 17, 2019

Scientific Reports, Jun 18, 2019

Visual impairment is common in people living with dementia and regular ophthalmological exams may... more Visual impairment is common in people living with dementia and regular ophthalmological exams may improve their quality of life. We evaluated visual function in a cohort of elderly individuals and analyzed its association with their degree of cognitive impairment. participants underwent neurological and neuropsychological exams, neuro-ophthalmological assessment (visual acuity, intraocular pressure, rates of past ophthalmological pathologies, use of ocular correction, treatments and surgeries) and optical coherence tomography (OCT) scan. We analyzed differences in ophthalmological characteristics among diagnostic groups. The final sample of 1746 study participants aged ≥ 50 comprised 229 individuals with Subjective Cognitive Decline (SCD), 695 with mild cognitive impairment (MCI) and 833 with Dementia (Alzheimer disease: n = 660; vascular dementia: n = 92, Lewy body dementia: n = 34; frontotemporal dementia: n = 19 and other: n = 28). Age, gender and education were used as covariates. patients with Dementia, compared to those with sCD and MCI, presented worse visual acuity (p < 0.001), used less visual correction (p = 0.02 and p < 0.001, respectively) and fewer ophthalmological treatments (p = 0.004 and p < 0.001, respectively) and underwent fewer ocular surgeries (p = 0.009 and p < 0.001, respectively). OCT image quality worsened in parallel to cognitive decline (Dementia vs sCD: p = 0.008; Dementia vs MCI: p < 0.001). No group differences in past ophthalmological disorders or abnormal OCT findings were detected. Efforts should be made to ensure dementia patients undergo regular ophthalmological assessments to correct their visual function in order to improve their quality of life. Alzheimer's Disease (AD), the leading cause of dementia in the elderly, is a neurodegenerative condition that irreversibly impairs cognition 1. AD symptoms progressively develop over time and include memory loss, impairment of judgment, disorientation, personality changes and emotional disturbances 2. Visual abnormalities are also common in AD, leading to falls, confusion and difficulty with activities of daily living. In combination with visual hallucinations, poor vision can affect an individual's autonomy and quality of life 3. Large population studies have identified a higher prevalence of age-related visual problems among elderly people with dementia compared to the general population 4. The burden of both visual impairment and cognitive decline is expected to rise in the near future due to the increase in life expectancy 5,6 .