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BACKGROUND AND PURPOSE: Behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD), such as mood, psychotic, and autism spectrum disorders, share similar clinical characteristics of behavior and social cognition. Better understanding of clinical progression in bvFTD and PPD is essential for adequate disease monitoring and trial design. METHODS: In this longitudinal study (N = 89), patients with bvFTD and PPD with at least one follow-up assessment were included from the Social Brain Project of the Alzheimer Center Amsterdam. Behavioral change and social cognitive decline were assessed via informant-rated questionnaires (Cambridge Behavioral Inventory-Revised, Frontal Behavioral Inventory [FBI], Stereotypy Rating Inventory, Frontotemporal Dementia Rating Scale, Revised Self-Monitoring Scale [RSMS]-caregiver) and patient assessment (Ekman 60-Faces Test, RSMS-patient, Emotional Contagion Scale). Clinical trajectories (median = 1.4 years, interquartile range = 1.0-2.2) were examined using linear mixed models. In a subsample, associations with baseline serum neurofilament light (sNfL) were examined. RESULTS: At baseline, behavioral and social cognitive symptoms were similar between diagnosis groups, except for poorer emotion recognition in bvFTD. Over time, behavioral symptoms worsened in bvFTD, whereas most measures remained stable and the FBI improved in PPD. Regarding social cognition, emotion recognition and caregiver-reported socioemotional sensitivity worsened in bvFTD and remained stable in PPD. Patient-reported social cognitive measures did not change over time. Higher sNfL was associated with faster behavioral change. CONCLUSIONS: Trajectories of behavior and social cognition differentiate bvFTD from PPD, provided that social cognition is not patient-reported. Therefore, we stress the need to optimize longitudinal social cognitive assessment in bvFTD. sNfL may be a useful prognostic marker of behavioral progression in neuropsychiatric populations.
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The behavioural variant of Alzheimer's disease (bvAD) is characterized by early predominant behavioural changes, mimicking the behavioural variant of frontotemporal dementia (bvFTD), which is characterized by social cognition deficits and altered biometric responses to socioemotional cues. These functions remain understudied in bvAD. We investigated multiple social cognition components (i.e. emotion recognition, empathy, social norms and moral reasoning), using the Ekman 60 faces test, Interpersonal Reactivity Index, empathy eliciting videos, Social Norms Questionnaire and moral dilemmas, while measuring eye movements and galvanic skin response. We compared 12 patients with bvAD with patients with bvFTD (n = 14), typical Alzheimer's disease (tAD, n = 13) and individuals with subjective cognitive decline (SCD, n = 13), using ANCOVAs and age- and sex-adjusted post hoc testing. Patients with bvAD (40.1 ± 8.6) showed lower scores on the Ekman 60 faces test compared to individuals with SCD (49.7 ± 5.0, P < 0.001), and patients with tAD (46.2 ± 5.3, P = 0.05) and higher scores compared to patients with bvFTD (32.4 ± 7.3, P = 0.002). Eye-tracking during the Ekman 60 faces test revealed no differences in dwell time on the eyes (all P > 0.05), but patients with bvAD (18.7 ± 9.5%) and bvFTD (19.4 ± 14.3%) spent significantly less dwell time on the mouth than individuals with SCD (30.7 ± 11.6%, P < 0.01) and patients with tAD (32.7 ± 12.1%, P < 0.01). Patients with bvAD (11.3 ± 4.6) exhibited lower scores on the Interpersonal Reactivity Index compared with individuals with SCD (15.6 ± 3.1, P = 0.05) and similar scores to patients with bvFTD (8.7 ± 5.6, P = 0.19) and tAD (13.0 ± 3.2, P = 0.43). The galvanic skin response to empathy eliciting videos did not differ between groups (all P > 0.05). Patients with bvAD (16.0 ± 1.6) and bvFTD (15.2 ± 2.2) showed lower scores on the Social Norms Questionnaire than patients with tAD (17.8 ± 2.1, P < 0.05) and individuals with SCD (18.3 ± 1.4, P < 0.05). No group differences were observed in scores on moral dilemmas (all P > 0.05), while only patients with bvFTD (0.9 ± 1.1) showed a lower galvanic skin response during personal dilemmas compared with SCD (3.4 ± 3.3 peaks per min, P = 0.01). Concluding, patients with bvAD showed a similar although milder social cognition profile and a similar eye-tracking signature to patients with bvFTD and greater social cognition impairments and divergent eye movement patterns compared with patients with tAD. Our results suggest reduced attention to salient facial features in these phenotypes, potentially contributing to their emotion recognition deficits.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Humanos , Enfermedad de Alzheimer/psicología , Cognición/fisiología , Cognición Social , Pruebas Neuropsicológicas , Emociones , Demencia Frontotemporal/psicologíaRESUMEN
BACKGROUND: Patients displaying clinical features of behavioural variant of frontotemporal dementia (bvFTD) but lacking both neuroimaging abnormalities and clinical progression are considered to represent the phenocopy syndrome of bvFTD (phFTD). Extensive clinical overlap between early phase bvFTD and phFTD hampers diagnostic distinction. We aimed to assess the diagnostic value of clinician-rated, self-reported and caregiver-reported symptoms for clinical distinction between phFTD and bvFTD. METHODS: There were 33 phFTD and 95 probable bvFTD patients included in the study (total N = 128). Clinician-rated, self-reported tests and caregiver-reported symptoms were compared between phFTD and bvFTD on social cognition, behaviour, mood and activities of daily living (ADL). Scores were compared between groups, followed by multiple logistic regression analysis, adjusted for age and sex. Receiver operating characteristic curves were plotted to assess diagnostic value. RESULTS: Using clinician-rated and self-reported tests, phFTD patients performed better on facial emotion recognition and reported more depressive symptoms. Caregiver-reported behavioural symptoms indicated higher behavioural and ADL impairment in phFTD compared to bvFTD. Facial emotion recognition provided highest diagnostic accuracy for distinction of phFTD from bvFTD (area under the curve (AUC) 0.813 95% CI 0.735-0.892, P < 0.001, sensitivity 81%, specificity 74%) followed by depressive symptoms (AUC 0.769 95% 0.674-0.864, P < 0.001 sensitivity 81%, specificity of 63%). CONCLUSION: Social cognition tests are most suitable for distinction of phFTD from bvFTD. Caregiver-reported questionnaires and phFTD diagnosis seemed inversely correlated, showing more symptoms in phFTD. Further research is needed on phFTD aetiology and in caregivers taking into account disease burden to assess what explains this discrepancy between clinician-rated and caregiver-based tools.
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Demencia Frontotemporal , Pruebas Neuropsicológicas , Cognición Social , Humanos , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/psicología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Cuidadores/psicología , Actividades Cotidianas/psicología , Diagnóstico Diferencial , Autoinforme , FenotipoRESUMEN
BACKGROUND AND PURPOSE: Early diagnosis of behavioral variant frontotemporal dementia (bvFTD) is challenging due to symptomatic overlap with primary psychiatric disorders (PPD). As emotion recognition deficits are early and key features of bvFTD, the aim was to explore processes driving social cognition deficits that may aid in the differentiation between bvFTD and PPD. METHODS: The total sample (N = 51) included 18 patients with bvFTD, 11 patients with PPD (mood, autism spectrum and psychotic disorders) and 22 controls from the Alzheimer Center Amsterdam of the Amsterdam UMC. Emotion recognition was assessed with the Ekman 60 Faces test, during which eye tracking metrics were collected in the first 5 s a face was presented. Group differences in dwell time on the total image as well as the circumscribed eyes area and mouth area were analysed using ANOVA, with post hoc comparisons. RESULTS: Patients with bvFTD scored lowest, patients with PPD scored intermediate and controls scored highest on emotion recognition. During facial processing, patients with bvFTD spent less dwell time on the total image than controls (mean difference 11.3%, F(2, 48) = 6.095, p = 0.004; bvFTD-controls p = 0.001, 95% confidence interval [CI] -892.64, -239.70). Dwell time on the eyes area did not differ between diagnostic groups, whilst patients with bvFTD spent less dwell time on the mouth area than PPD patients (mean difference 10.7%; F(2, 48) = 3.423, p = 0.041; bvFTD-PPD p = 0.022, 95% CI -986.38, -79.47) and controls (mean difference 7.8%; bvFTD-controls p = 0.043, 95% CI -765.91, -12.76). CONCLUSIONS: In bvFTD, decreased emotion recognition may be related to reduced focus on facial hallmarks. These findings suggest a valuable role for biometrics in social cognition assessment and the differentiation between bvFTD and PPD.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Humanos , Demencia Frontotemporal/psicología , Pruebas Neuropsicológicas , Reconocimiento en Psicología , Emociones , Cognición , Enfermedad de Alzheimer/diagnósticoRESUMEN
BACKGROUND: Adequate detection of symptoms and disease progression in behavioural variant frontotemporal dementia (bvFTD) is complex. Dementia cohorts usually utilize cognitive and functional measures, which fail to detect dominant behavioural and social cognitive deficits in bvFTD. Moreover, since patients typically have a loss of insight, caregivers are important informants. This is the first qualitative study to investigate caregiver relevant symptoms during the disease course of bvFTD, aiming to improve tools for diagnosis, progression, and future clinical trials. METHODS: Informal caregivers of patients in different disease stages of bvFTD (N = 20) were recruited from the neurology outpatient clinic of the Amsterdam UMC and a patient organization for peer support in the Netherlands. Their perspectives on clinical relevance were thoroughly explored during individual semi-structured interviews. Inductive content analysis with open coding was performed by two researchers independently to establish overarching themes and patterns. RESULTS: Caregivers reported a variety of symptoms, in which (i) loss of emotional connection, (ii) preoccupation and restlessness, and (iii) apathy and dependency compose major themes of relevance for diagnosis and treatment. Within heterogeneous disease trajectories, symptom presence differed between stages and among individuals, which is relevant in the context of progression and outcome measures. Significant socio-emotional changes dominated in early stages, while severe cognitive, behavioural, and physical deterioration shifted focus from predominant personality change to quality of life in later stages. CONCLUSIONS: Caregiver perspectives on target symptoms in bvFTD differ according to clinical stage and patient-caregiver characteristics, with significant socio-emotional changes characterizing early stages. These findings call for more appropriate tools and symptomatic treatments, as well as a personalized approach in treatment of bvFTD and a focus on early stage interventions in clinical trial design.
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Cuidadores , Demencia Frontotemporal , Humanos , Cuidadores/psicología , Manejo de la Enfermedad , Demencia Frontotemporal/psicología , Demencia Frontotemporal/terapia , Ensayos Clínicos como Asunto , Proyectos de InvestigaciónRESUMEN
OBJECTIVES: Frontotemporal dementia (FTD) can present with changes in music appreciation. Research has suggested a relationship of altered music appreciation phenotypes with typical socio-emotional changes. We aimed to determine the prevalence and severity of music appreciation phenotypes in FTD and study the relationship with emotion recognition capacities in order to examine whether they could serve as a proxy for changes in socio-emotional functioning. METHODS/DESIGN: Based on reported musical changes in the literature, we developed an informant-based questionnaire to assess musical changes and a music test to assess music emotion recognition. Social cognition was assessed with the Ekman 60 faces test in a subgroup of patients (n = 23). Relationships between measures were assessed with linear regressions. RESULTS: We included 47 patients (44.7% female, mean age 65.0 ± 8.4, 31 behavioral variant FTD (bvFTD), 10 semantic dementia (SD), and six progressive nonfluent aphasia (PNFA)). Thirty-six caregivers were included in the music emotion recognition test as controls. Altered music appreciation phenotypes were observed in 79% of the FTD patients. Musicophilia was present in a third of bvFTD patients, and only in up to 10% in language FTD variants. Changes in music appreciation were not associated with decreased music emotion recognition or visual emotion recognition. Compared to controls, bvFTD performed worse on the music emotion recognition task (p < 0.003), and no differences were found with SD (p = 0.06) and PNFA patients (p = 0.8). CONCLUSIONS: Music appreciation phenotypes are highly prevalent in FTD patients. Future studies should further investigate the potential diagnostic value of changes in music processing.
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Demencia Frontotemporal , Música , Femenino , Demencia Frontotemporal/psicología , Humanos , Masculino , Pruebas Neuropsicológicas , Fenotipo , Proyectos PilotoRESUMEN
A clinical syndrome with neuropsychiatric features of bvFTD without neuroimaging abnormalities and a lack of decline is a phenocopy of bvFTD (phFTD). Growing evidence suggests that psychological, psychiatric and environmental factors underlie phFTD. We describe a patient diagnosed with bvFTD prior to the revision of the diagnostic guidelines of FTD. Repeated neuroimaging was normal and there was no FTD pathology at autopsy, rejecting the diagnosis. We hypothesize on etiological factors that on hindsight might have played a role. This case report contributes to the understanding of phFTD and adds to the sparse literature of the postmortem assessment of phFTD.
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Fluorodesoxiglucosa F18 , Demencia Frontotemporal , Humanos , Imagen por Resonancia Magnética , Neuroimagen , FenotipoRESUMEN
BACKGROUND: Lack of early molecular biomarkers in sporadic behavioral variants of frontotemporal dementia (bvFTD) and its clinical overlap with primary psychiatric disorders (PPD) hampers its diagnostic distinction. Synaptic dysfunction is an early feature in bvFTD and identification of specific biomarkers might improve its diagnostic accuracy. Our goal was to understand the differential diagnostic potential of cerebrospinal fluid (CSF) synaptic biomarkers in bvFTD versus PPD and their specificity towards bvFTD compared with Alzheimer's disease (AD) and controls. Additionally, we explored the association of CSF synaptic biomarkers with social cognition, cognitive performance, and disease severity in these clinical groups. METHODS: Participants with probable bvFTD (n = 57), PPD (n = 71), AD (n = 60), and cognitively normal controls (n = 39) with available CSF, cognitive tests, and disease severity as frontotemporal lobar degeneration-modified clinical dementia rating scale (FTLD-CDR) were included. In a subset of bvFTD and PPD cases, Ekman 60 faces test scores for social cognition were available. CSF synaptosomal-associated protein 25 (SNAP25), neurogranin (Ng), neuronal pentraxin 2 (NPTX2), and glutamate receptor 4 (GluR4) were measured, along with neurofilament light (NfL), and compared between groups using analysis of covariance (ANCOVA) and logistic regression. Diagnostic accuracy was assessed using ROC analyses, and biomarker panels were selected using Wald's backward selection. Correlations with cognitive measures were performed using Pearson's partial correlation analysis. RESULTS: NPTX2 concentrations were lower in the bvFTD group compared with PPD (p < 0.001) and controls (p = 0.003) but not compared with AD. Concentrations of SNAP25 (p < 0.001) and Ng (p < 0.001) were elevated in patients with AD versus those with bvFTD and controls. The modeled panel for differential diagnosis of bvFTD versus PPD consisted of NfL and NPTX2 (AUC = 0.96, CI: 0.93-0.99, p < 0.001). In bvFTD versus AD, the modeled panel consisted of NfL, SNAP25, Ng, and GluR4 (AUC = 0.86, CI: 0.79-0.92, p < 0.001). In bvFTD, lower NPTX2 (Pearson's r = 0.29, p = 0.036) and GluR4 (Pearson's r = 0.34, p = 0.014) concentrations were weakly associated with worse performance of total cognitive score. Lower GluR4 concentrations were also associated with worse MMSE scores (Pearson's r = 0.41, p = 0.002) as well as with worse executive functioning (Pearson's r = 0.36, p = 0.011) in bvFTD. There were no associations between synaptic markers and social cognition or disease severity in bvFTD. CONCLUSION: Our findings of involvement of NTPX2 in bvFTD but not PPD contribute towards better understanding of bvFTD disease pathology.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Degeneración Lobar Frontotemporal , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/líquido cefalorraquídeo , Demencia Frontotemporal/patología , Degeneración Lobar Frontotemporal/diagnóstico , Curva ROC , Pruebas Neuropsicológicas , Biomarcadores/líquido cefalorraquídeoRESUMEN
Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by diverse and prominent changes in behavior and personality. One of the greatest challenges in bvFTD is to capture, measure and predict its disease progression, due to clinical, pathological and genetic heterogeneity. Availability of reliable outcome measures is pivotal for future clinical trials and disease monitoring. Detection of change should be objective, clinically meaningful and easily assessed, preferably associated with a biological process. The purpose of this scoping review is to examine the status of longitudinal studies in bvFTD, evaluate current assessment tools and propose potential progression markers. A systematic literature search (in PubMed and Embase.com) was performed. Literature on disease trajectories and longitudinal validity of frequently-used measures was organized in five domains: global functioning, behavior, (social) cognition, neuroimaging and fluid biomarkers. Evaluating current longitudinal data, we propose an adaptive battery, combining a set of sensitive clinical, neuroimaging and fluid markers, adjusted for genetic and sporadic variants, for adequate detection of disease progression in bvFTD.
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BACKGROUND: Neuropsychiatric symptoms (NPS) are prevalent in the early clinical stages of Alzheimer's disease (AD) according to proxy-based instruments. Little is known about which NPS clinicians report and whether their judgment aligns with proxy-based instruments. We used natural language processing (NLP) to classify NPS in electronic health records (EHRs) to estimate the reporting of NPS in symptomatic AD at the memory clinic according to clinicians. Next, we compared NPS as reported in EHRs and NPS reported by caregivers on the Neuropsychiatric Inventory (NPI). METHODS: Two academic memory clinic cohorts were used: the Amsterdam UMC (n = 3001) and the Erasmus MC (n = 646). Patients included in these cohorts had MCI, AD dementia, or mixed AD/VaD dementia. Ten trained clinicians annotated 13 types of NPS in a randomly selected training set of n = 500 EHRs from the Amsterdam UMC cohort and in a test set of n = 250 EHRs from the Erasmus MC cohort. For each NPS, a generalized linear classifier was trained and internally and externally validated. Prevalence estimates of NPS were adjusted for the imperfect sensitivity and specificity of each classifier. Intra-individual comparison of the NPS classified in EHRs and NPS reported on the NPI were conducted in a subsample (59%). RESULTS: Internal validation performance of the classifiers was excellent (AUC range: 0.81-0.91), but external validation performance decreased (AUC range: 0.51-0.93). NPS were prevalent in EHRs from the Amsterdam UMC, especially apathy (adjusted prevalence = 69.4%), anxiety (adjusted prevalence = 53.7%), aberrant motor behavior (adjusted prevalence = 47.5%), irritability (adjusted prevalence = 42.6%), and depression (adjusted prevalence = 38.5%). The ranking of NPS was similar for EHRs from the Erasmus MC, although not all classifiers obtained valid prevalence estimates due to low specificity. In both cohorts, there was minimal agreement between NPS classified in the EHRs and NPS reported on the NPI (all kappa coefficients < 0.28), with substantially more reports of NPS in EHRs than on NPI assessments. CONCLUSIONS: NLP classifiers performed well in detecting a wide range of NPS in EHRs of patients with symptomatic AD visiting the memory clinic and showed that clinicians frequently reported NPS in these EHRs. Clinicians generally reported more NPS in EHRs than caregivers reported on the NPI.
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Enfermedad de Alzheimer , Apatía , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/psicología , Registros Electrónicos de Salud , Procesamiento de Lenguaje Natural , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is generally considered a young-onset dementia, although age at onset is highly variable. While several studies indicate clinical differences regarding age at onset, no biomarker validated cohort studies with updated clinical criteria have been performed. OBJECTIVE: We aimed to examine behavior, cognition, and mortality over the full age spectrum in a cohort of bvFTD patients with neuroimaging, genetic, or histopathological confirmation and exclusion of positive Alzheimer's disease biomarkers or severe cerebrovascular damage. METHODS: In total, 315 patients with a clinical diagnosis of probable or definite bvFTD were included from the Amsterdam Dementia Cohort and grouped into quartiles by age-at-diagnosis. Neuropsychiatric symptoms and cognitive functioning were assessed with the neuropsychiatric inventory, the geriatric depression scale and a neuropsychological test battery. Data on mortality was obtained from the Dutch municipal register. Associations between age-at-diagnosis and clinical features and mortality risk were examined. RESULTS: Age-at-diagnosis ranged from 26 to 85 years and established quartiles with mean ages of 52±6, 61±2, 66±2, and 74±3 years. In the total sample, 44.4%exceeded an age of 65 years at time of diagnosis. Earlier age-at-diagnosis was associated with more severe behavioral symptoms, while later age-at-diagnosis was associated with more severe memory impairment. Unexpectedly, mortality risk was not associated with age-at-diagnosis. CONCLUSION: In bvFTD, symptom profile is associated with age-at-diagnosis. This should be taken into account with regard to diagnostics, patient management, and trial design. Additionally, based on our sample, the prevalence of late-onset bvFTD is higher than generally thought.
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Demencia Frontotemporal/fisiopatología , Mortalidad , Pruebas Neuropsicológicas , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Ansiedad/fisiopatología , Ansiedad/psicología , Apatía/fisiología , Deluciones/fisiopatología , Deluciones/psicología , Femenino , Demencia Frontotemporal/psicología , Alucinaciones/fisiopatología , Alucinaciones/psicología , Humanos , Inhibición Psicológica , Genio Irritable/fisiología , Masculino , Trastornos de la Memoria/fisiopatología , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Trastornos del Humor/fisiopatología , Trastornos del Humor/psicología , Fenotipo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Reported sex distributions differ between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that has resulted in varying demographics. OBJECTIVE: Our aim was to determine the sex distribution of sporadic and genetic FTD cases and its subtypes in an international cohort. METHODS: We included 910 patients with behavioral variant frontotemporal dementia (bvFTD; nâ=â654), non-fluent variant primary progressive aphasia (nfvPPA; nâ=â99), semantic variant primary progressive aphasia (svPPA; nâ=â117), and right temporal variant frontotemporal dementia (rtvFTD; nâ=â40). We compared sex distribution between genetic and sporadic FTD using χ2-tests. RESULTS: The genetic FTD group consisted of 51.2% males, which did not differ from sporadic FTD (57.8% male, pâ=â0.08). In the sporadic bvFTD subgroup, males were predominant in contrast to genetic bvFTD (61.6% versus 52.9% males, pâ=â0.04). In the other clinical FTD subgroups, genetic cases were underrepresented and within the sporadic cases the sex distribution was somewhat equal. CONCLUSION: The higher male prevalence in sporadic bvFTD may provide important clues for its differential pathogenesis and warrants further research.
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Afasia Progresiva Primaria , Demencia Frontotemporal , Distribución por Sexo , Femenino , Demencia Frontotemporal/clasificación , Demencia Frontotemporal/genética , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SemánticaRESUMEN
Nutrition is one of the modifiable risk factors for cognitive decline and Alzheimer's disease (AD) dementia, and is therefore highly relevant in the context of prevention. However, knowledge of dietary quality in clinical populations on the spectrum of AD dementia is lacking, therefore we studied the association between dietary quality and cognitive impairment in Alzheimer's disease (AD) dementia, mild cognitive impairment (MCI) and controls. We included 357 participants from the NUDAD project (134 AD dementia, 90 MCI, 133 controls). We assessed adherence to dietary guidelines (components: vegetables, fruit, fibers, fish, saturated fat, trans-fat, salt, and alcohol), and cognitive performance (domains: memory, language, visuospatial functioning, attention, and executive functioning). In the total population, linear regression analyses showed a lower vegetable intake is associated with poorer global cognition, visuospatial functioning, attention and executive functioning. In AD dementia, lower total adherence to dietary guidelines and higher alcohol intake were associated with poorer memory, a lower vegetable intake with poorer global cognition and executive functioning, and a higher trans-fat intake with poorer executive functioning. In conclusion, a suboptimal diet is associated with more severely impaired cognition-this association is mostly attributable to a lower vegetable intake and is most pronounced in AD dementia.
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Enfermedad de Alzheimer/etiología , Disfunción Cognitiva/etiología , Dieta Saludable , Ingestión de Alimentos , Fenómenos Fisiológicos Nutricionales del Anciano , Conducta Alimentaria , Desnutrición/complicaciones , Ingesta Diaria Recomendada , Verduras , Consumo de Bebidas Alcohólicas/efectos adversos , Enfermedad de Alzheimer/psicología , Cognición , Disfunción Cognitiva/psicología , Grasas de la Dieta/efectos adversos , Función Ejecutiva , Femenino , Humanos , Masculino , Cooperación del Paciente , Factores de Riesgo , Ácidos Grasos trans/efectos adversosRESUMEN
INTRODUCTION: Weight loss is associated with higher mortality and progression of cognitive decline, but its associations with magnetic resonance imaging (MRI) changes related to Alzheimer's disease (AD) are unknown. METHODS: We included 412 patients from the NUDAD project, comprising 129 with AD dementia, 107 with mild cognitive impairment (MCI), and 176 controls. Associations between nutritional status and MRI measures were analyzed using linear regression, adjusted for age, sex, education, cognitive functioning, and cardiovascular risk factors. RESULTS: Lower body mass index (BMI), fat mass (FM), and fat free mass index were associated with higher medial temporal atrophy (MTA) scores. Lower BMI, FM, and waist circumference were associated with more microbleeds. Stratification by diagnosis showed that the observed associations with microbleeds were only significant in MCI. DISCUSSION: Lower indicators of nutritional status were associated with more MTA and microbleeds, with largest effect sizes in MCI.
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As malnutrition is common in patients with Alzheimer's disease (AD), we evaluated nutritional status and body composition of patients with AD, mild cognitive impairment (MCI) and controls, and studied associations of AD biomarkers and cognitive performance with nutritional status and body composition. We included 552 participants, of which 198 patients had AD, 135 patients had MCI and 219 controls. We assessed nutritional status (mini nutritional assessment (MNA)) and body composition (body mass index (BMI), fat-free mass (FFM) and waist circumference). Linear regression analyses (adjusted for age, gender and education where appropriate) were applied to test associations of AD biomarkers and cognitive performance on five domains with nutritional parameters (dependent). Patients with MCI and AD had a lower BMI and MNA score than controls. Worse performance in all cognitive domains was associated with lower MNA score, but not with body composition. AD biomarkers were associated with MNA score, BMI and waist circumference, and associations with MNA score remained after adjustment for cognitive performance. Both AD biomarkers and cognitive performance were associated with nutritional status, associations with AD biomarkers remained after adjustment for cognition. Our data suggest that malnutrition is not only related to impaired cognition but also to AD pathology.