Authors: Rodríguez-Gómez, Octavio | Abdelnour, Carla | Jessen, Frank | Valero, Sergi | Boada, Merçé
Article Type: Review Article
Abstract: Subjective cognitive decline (SCD) has been proposed as a marker of neurodegeneration in cognitively normal elderly. This idea is supported by the growing evidence that SCD is associated with Alzheimer’s disease (AD) biomarkers and increases the risk of future cognitive impairment. Nevertheless, this evidence is not complete, since other studies have not found these associations. This discrepancy could have a methodological basis. It is well known that across the broad spectrum of degenerative disease from healthy controls to dementia, the research setting affects key characteristics of the sample such as age, educational level, or family history of dementia. However, virtually …no studies have specifically tested the influence of sampling and recruitment methods in SCD research. Population-based samples are less biased and therefore they probably are more suitable for the study of memory complaints as a symptom at the population level. On the other hand, the memory clinic setting could introduce a set of biases that make these patients more likely to develop cognitive impairment. Thus, memory clinic would be the most cost-effective context in which to study the phenomenology of SCD due to AD and eventually recruit patients for secondary prevention trials. However, this general hypothesis needs to be tested. Studies that compare samples of patients with SCD from different settings are necessary. Sometimes it is difficult for patients with subtle forms of cognitive impairment to access specialized diagnostic centers. Based in our experience we state that Open House type initiatives may be useful for attracting these individuals to memory clinics. Show more
Keywords: Alzheimer’s disease, epidemiologic research design, epidemiologic studies, patient selection, risk, sampling, selection bias, subjective cognitive decline
DOI: 10.3233/JAD-150189
Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S99-S107, 2015
Authors: Espinosa, Ana | Alegret, Montserrat | Valero, Sergi | Vinyes-Junqué, Georgina | Hernández, Isabel | Mauleón, Ana | Rosende-Roca, Maitée | Ruiz, Agustín | López, Oscar | Tárraga, Lluís | Boada, Mercè
Article Type: Research Article
Abstract: The most recent studies about mild cognitive impairment (MCI) are focused on the search for factors that make patients more vulnerable to conversion to dementia, mainly Alzheimer's disease (AD). The aim of this study was to determine which neuropsychological test performances, including episodic memory profiles, and genetic risk factors (APOE ε4) better predict early conversion to dementia among the four MCI subtypes. Data from 550 MCI patients were analyzed for the purpose of this study and were classified according to Petersen's criteria (2004), and also taking into account the absence (probable MCI) or presence (possible MCI) of comorbidities that could …explain cognitive deficits. MCI cases were divided into Probable amnestic (Pr-aMCI) (n = 115), probable non-amnestic (Pr-naMCI) (n = 37), possible amnestic (Pss-aMCI) (n = 234), and possible non-amnestic (Pss-naMCI) (n = 164), single or multiple domain. In the whole MCI sample, regression analysis showed that low performances on Orientation, Verbal Delayed Recall of the Word List Learning test from WMS-III, and Luria's Clock test were associated with conversion to dementia, independently of APOE ε4 allele. Cox proportional-hazards showed that the Probable MCI subtype, presence of storage memory impairment, multiple domain condition, and presence of at least one ε4 allele increased the risk of conversion to dementia. Multivariate survival and Kapplan-Meier analyses showed that the Pr-aMCI with storage memory impairment had the most and closest risk of conversion to dementia. In conclusion, the Pr-aMCI subset of patients had 8.5 times more risk of converting to dementia than the Pss-naMCI group, who displayed the slowest conversion rate to dementia. Show more
Keywords: Amnestic, cognition, dementia conversion, genetics, mild cognitive impairment, risk factors
DOI: 10.3233/JAD-122002
Citation: Journal of Alzheimer's Disease, vol. 34, no. 3, pp. 769-780, 2013
Authors: Alegret, Montserrat | Peretó, Mar | Pérez, Alba | Valero, Sergi | Espinosa, Ana | Ortega, Gemma | Hernández, Isabel | Mauleón, Ana | Rosende-Roca, Maitée | Vargas, Liliana | Rodríguez-Gómez, Octavio | Abdelnour, Carla | Berthier, Marcelo L. | Bak, Thomas H. | Ruíz, Agustín | Tárraga, Lluís | Boada, Mercè
Article Type: Research Article
Abstract: Background: Verb fluency (VF) is the less commonly used fluency test, despite several studies suggesting its potential as a neuropsychological assessment tool. Objective: To investigate the presence of VF deficits in mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD) dementia; to assess the usefulness of VF in the detection of cognitively healthy (CH) people who will convert to MCI, and from MCI to dementia; and to establish the VF cut-offs useful in the cognitive assessment of Spanish population. Methods: 568 CH, 885 MCI, and 367 mild AD dementia individuals were administered the VF test and a complete neuropsychological battery. …Longitudinal analyses were performed in 231 CH and 667 MCI subjects to search for VF predictors of diagnosis conversion. Results: A worsening on VF performance from CH, MCI to AD dementia groups was found. Lower performances on VF were significantly related to conversion from CH to MCI/MCI to dementia. When the effect of time to conversion was analyzed, a significant effect of VF was found on the faster conversion from CH to MCI, but not from MCI to dementia. Moreover, VF cut-off scores and sensitivity/specificity values were calculated for 6 conditions (3 age ranges by 2 educational levels). Conclusion: The VF test may be a useful tool for the differential diagnosis of cognitive failure in the elderly. Since VF deficits seem to take place in early stages of the disease, it is a suitable neuropsychological tool for the detection not only of CH people who will convert to MCI, but also from MCI to dementia. Show more
Keywords: Alzheimer’s disease, cognitively healthy, mild cognitive impairment, verb fluency, verbal fluency
DOI: 10.3233/JAD-170826
Citation: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 611-619, 2018
Authors: Alegret, Montserrat | Vinyes-Junqué, Georgina | Boada, Mercè | Martínez-Lage, Pablo | Cuberas, Gemma | Espinosa, Ana | Roca, Isabel | Hernández, Isabel | Valero, Sergi | Rosende-Roca, Maitée | Mauleón, Ana | Becker and, James T. | Tárraga, Lluís
Article Type: Research Article
Abstract: Visuoperceptual processing is impaired early in the clinical course of Alzheimer's disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in mild cognitive impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal, and prefrontal regions have been found in early AD and MCI patients. The objectives of this study were to confirm the role of the 15-OT in the diagnosis of MCI and AD and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD, and normal aging. Forty-two AD, 42 MCI, and 42 healthy elderly control subjects underwent a …brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. Show more
Keywords: Alzheimer's disease, brain SPECT, cerebral perfusion, mild cognitive impairment, visuoperception
DOI: 10.3233/JAD-2010-091069
Citation: Journal of Alzheimer's Disease, vol. 21, no. 2, pp. 557-567, 2010
Authors: Alegret, Montserrat | Cuberas-Borrós, Gemma | Espinosa, Ana | Valero, Sergi | Hernández, Isabel | Ruíz, Agustín | Becker, James T. | Rosende-Roca, Maitée | Mauleón, Ana | Sotolongo, Oscar | Castell-Conesa, Joan | Roca, Isabel | Tárraga, Lluís | Boada, Mercè
Article Type: Research Article
Abstract: Background: There is a range of factors that predict the development of Alzheimer’s disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI). Objectives: To identify the neuropsychological, genetic, and functional brain imaging data that best predict conversion to AD dementia in patients with amnestic MCI. Methods: From an initial group of 42 amnestic MCI patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25 converters, 14 non-converters) were followed for 4 years, and 36 had APOE ε4 genotyping. Baseline neuropsychological data and brain SPECT data were used to predict which of the MCI patients would develop dementia by …the end of the 4 years of observation. Results: The MCI patients who had converted to AD dementia had poorer performance on long-term visual memory and Semantic Fluency tests. The MCI subjects who developed dementia were more likely to carry at least one copy of the APOE ε4 allele (Hazard Risk = 4.22). There was lower brain perfusion in converters than non-converters, mainly in postcentral gyrus. An additional analysis of the SPECT data found differences between the MCI subjects and controls in the posterior cingulate gyrus and the basal forebrain. When the brain imaging and neuropsychological test data were combined in the same Cox regression model, only the neuropsychological test data were significantly associated with time to dementia. Conclusion: Although the presence of reduced brain perfusion in postcentral gyrus and basal forebrain indicated an at-risk condition, it was the extent of memory impairment that was linked to the speed of decline from MCI to AD. Show more
Keywords: Alzheimer's disease, brain SPECT, cerebral perfusion, four-year follow-up, longitudinal, mild cognitive impairment, prospective, visual memory
DOI: 10.3233/JAD-132516
Citation: Journal of Alzheimer's Disease, vol. 41, no. 3, pp. 739-748, 2014
Authors: Alegret, Montserrat | Cuberas-Borrós, Gemma | Vinyes-Junqué, Georgina | Espinosa, Ana | Valero, Sergi | Hernández, Isabel | Roca, Isabel | Ruíz, Agustín | Rosende-Roca, Maitée | Mauleón, Ana | Becker, James T. | Castell-Conesa, Joan | Tárraga, Lluís | Boada, Mercè
Article Type: Research Article
Abstract: The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual impairment from normal aging through Alzheimer's disease (AD) and correlates with temporo-parietal perfusion. The objectives of this study were to analyze progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and its correlates with cognition and single photon emission computerized tomography (SPECT), as well as to examine neuropsychological and SPECT differences between the MCI patients who developed AD and those who did not. From the initial 126 participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two …years. The progression of cognitive and SPECT scores during this period was compared between groups, and baseline data between converters and non-converters. The 15-OT was the only measure of progression that differed between the three groups; worsening scores on 15-OT were associated with worsening in verbal and visual retention, and decreased perfusion on left postsubicular area. In the MCI patients, cerebral perfusion fell over the two years in medial-posterior cingulate and fronto-temporo-parietal regions; AD showed extensive changes involving almost all cerebral regions. No SPECT changes were detected in controls. At baseline, the MCI patients who developed AD differed from non-converters in verbal recognition memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to provide a potential measure to differentiate between normal aging, MCI, and AD. Worsening on 15-OT was related to decreased perfusion in postsubicular area; but further longitudinal studies are needed to determine the contribution of 15-OT as a predictor of AD from MCI. Show more
Keywords: 15-objects test, Alzheimer's disease, brain SPECT, cerebral perfusion, longitudinal, mild cognitive impairment, prospective, two-year follow-up, visuoperception
DOI: 10.3233/JAD-2012-111850
Citation: Journal of Alzheimer's Disease, vol. 30, no. 1, pp. 109-120, 2012
Authors: Alegret, Montserrat | Rodríguez, Octavio | Espinosa, Ana | Ortega, Gemma | Sanabria, Angela | Valero, Sergi | Hernández, Isabel | Rosende-Roca, Maitée | Vargas, Liliana | Abdelnour, Carla | Mauleón, Ana | Gailhajanet, Anna | Martín, Elvira | Tárraga, Lluís | Rentz, Dorene M. | Amariglio, Rebecca E. | Ruíz, Agustín | Boada, Mercè
Article Type: Research Article
Abstract: BACKGROUND: Subjective memory impairment (SMI) refers to subjective awareness of initial memory decline undetectable with existing standardized cognitive tests. The Face Name Associative Memory Exam (FNAME) was created to detect memory deficits in individuals with preclinical Alzheimer’s disease (AD). We reported normative data of a Spanish version of FNAME (S-FNAME) in cognitively normal (CN) Spanish-speaking subjects >49. OBJECTIVE: To determine whether higher SMI [a modification of Memory Failures Everyday (MFE-30)] was related to worse memory performance (S-FNAME) or associated with greater affective symptoms in subjects >49; and whether MFE-30 and FNAME were able to discriminate between CN and mild cognitive …impairment (MCI) subjects. METHODS: 317 subjects (CN = 196, MCI = 121) were included in the analysis because they attended the annual “Open House Initiative” at Memory Clinic Fundació ACE, were >49 years, literate, received S-FNAME, MFE-30, and Hospital Anxiety and Depression Scale, had Mini-Mental State Examination scores ≥27, and returned to complete a comprehensive diagnostic assessment. RESULTS: MFE-30 scores were associated with affective symptoms but not with S-FNAME performance. S-FNAME scores were related to performance on memory variables of NBACE (neuropsychological battery used in Fundació ACE). Although the MCI group showed significantly higher MFE-30 and worse S-FNAME scores than the CN group, their discriminability values were similar (Sensitivity: 49.6 versus 52.9; Specificity: 85.1 versus 83.6, respectively). CONCLUSIONS: SMI was more related to depressive symptoms than to S-FNAME memory performance; and S-FNAME scores were related to other episodic memory test performances, but neither to affective symptoms nor to SMI. MFE-30 and S-FNAME are not optimal for discriminating between CN and MCI groups. Longitudinal follow-up will determine if lower S-FNAME and higher SMI are related to increased risk of AD. Show more
Keywords: Episodic memory, FNAME, neuropsychology, preclinical Alzheimer’s disease, subjective memory impairment
DOI: 10.3233/JAD-150594
Citation: Journal of Alzheimer's Disease, vol. 48, no. 4, pp. 1109-1117, 2015
Authors: Ibarria, Marta | Alegret, Montserrat | Valero, Sergi | Morera, Amèrica | Guitart, Marina | Cañabate, Pilar | Moreno, Mariola | Lara, Susana | Diego, Susana | Hernández, Joan | Tantinyá, Natàlia | Vera, Maribel | Hernández, Isabel | Becker, James T. | Ruíz, Agustín | Boada, Mercè | Tárraga, Lluís
Article Type: Research Article
Abstract: Background: The existing pharmacological treatments for Alzheimer’s disease (AD) can only slow the progression of symptoms or delay admission to long-term care facilities. The beneficial effects of non-drug treatments are poorly studied. Objective: To describe the effects of an Integrated Psychostimulation Program (IPP) in patients with mild-moderate AD treated with acetylcholinesterase inhibitors; and to identify factors related to greater benefit of the IPP. Methods: 206 patients (mean age = 75.9 years; MMSE = 19.6) were evaluated before starting the IPP and 3, 6, 9, and 12 months later. Measures included: Mini-Mental State Examination (MMSE), Cognitive Subscale of Alzheimer’s Disease Assessment Scale (ADAS-Cog), Rapid Disability …Rating Scale (RDRS-2), and Neuropsychiatric Inventory Questionnaire (NPI-Q). Results: Patients remained cognitively stable (MMSE/ADAS-Cog) for more than 6 months and significantly worsened at 9-month and 12-month follow-ups, without clinically significant functional changes (RDRS-2) or psychiatric symptoms(NPI-Q). The mean annual change on MMSE and ADAS-Cog were 2.06 and 3.56 points, respectively, lower than the annual decline demonstrated previously in similar patients (2.4 and 4.5, respectively). 42.7% of patients maintained or improved global cognitive scores between baseline and 12-month follow-up. The patients who maintained cognitive functions were older than those who did not (77.5 versus 74.7 years). Conclusions: The IPP may be an effective treatment to maintain cognition, functionality, and psychiatric symptoms in AD patients pharmacologically treated, and older age seems to increase beneficial effects of IPP. Show more
Keywords: Alzheimer’s disease, cognition, cognitive stimulation, dementia, functionality, Integral Psychostimulation Program, non-pharmacological therapy
DOI: 10.3233/JAD-150455
Citation: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 559-566, 2016
Authors: Alegret, Montserrat | García-Gutiérrez, Fernando | Muñoz, Nathalia | Espinosa, Ana | Ortega, Gemma | Lleonart, Núria | Rodríguez, Isabel | Rosende-Roca, Maitee | Pytel, Vanesa | Cantero-Fortiz, Yahveth | Rentz, Dorene M. | Marquié, Marta | Valero, Sergi | Ruiz, Agustín | Butler, Christopher | Boada, Mercè
Article Type: Research Article
Abstract: Background: The FACEmemory® online platform comprises a complex memory test and sociodemographic, medical, and family questions. This is the first study of a completely self-administered memory test with voice recognition, pre-tested in a memory clinic, sensitive to Alzheimer’s disease, using information and communication technologies, and offered freely worldwide. Objective: To investigate the demographic and clinical variables associated with the total FACEmemory score, and to identify distinct patterns of memory performance on FACEmemory. Methods: Data from the first 3,000 subjects who completed the FACEmemory test were analyzed. Descriptive analyses were applied to demographic, FACEmemory, and medical and family variables; t -test …and chi-square analyses were used to compare participants with preserved versus impaired performance on FACEmemory (cut-off = 32); multiple linear regression was used to identify variables that modulate FACEmemory performance; and machine learning techniques were applied to identify different memory patterns. Results: Participants had a mean age of 50.57 years and 13.65 years of schooling; 64.07% were women, and 82.10% reported memory complaints with worries. The group with impaired FACEmemory performance (20.40%) was older, had less schooling, and had a higher prevalence of hypertension, diabetes, dyslipidemia, and family history of neurodegenerative disease than the group with preserved performance. Age, schooling, sex, country, and completion of the medical and family history questionnaire were associated with the FACEmemory score. Finally, machine learning techniques identified four patterns of FACEmemory performance: normal, dysexecutive, storage, and completely impaired. Conclusions: FACEmemory is a promising tool for assessing memory in people with subjective memory complaints and for raising awareness about cognitive decline in the community. Show more
Keywords: Alzheimer’s disease, community, computerized assessment, early detection, memory, memory impairment, new technologies, patient engagement, subjective memory complaints
DOI: 10.3233/JAD-230983
Citation: Journal of Alzheimer's Disease, vol. 97, no. 3, pp. 1173-1187, 2024
Authors: Alegret, Montserrat | Espinosa, Ana | Ortega, Gemma | Pérez-Cordón, Alba | Sanabria, Ángela | Hernández, Isabel | Marquié, Marta | Rosende-Roca, Maitée | Mauleón, Ana | Abdelnour, Carla | Vargas, Liliana | de Antonio, Ester Esteban | López-Cuevas, Rogelio | Tartari, Juan Pablo | Alarcón-Martín, Emilio | Tárraga, Lluís | Ruiz, Agustín | Boada, Mercè | Valero, Sergi
Article Type: Research Article
Abstract: 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 home-to-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. Show more
Keywords: Alzheimer’s disease, cognitive impairment, construct validity, face-to-face, home-to-home, invariance, neuropsychological assessment, telemedicine, teleneuropsychology
DOI: 10.3233/JAD-201389
Citation: Journal of Alzheimer's Disease, vol. 81, no. 4, pp. 1541-1553, 2021
