Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders.

Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

Diagnostic validity of the Alzheimer's disease functional assessment and change scale in mild cognitive impairment and mild to moderate Alzheimer's disease.

BACKGROUND: The Alzheimer's Disease Functional Assessment and Change Scale (ADFACS) is a functional assessment instrument widely used in clinical research. AIMS: To test the diagnostic and concurrent validity of the Spanish version of this scale and to describe the functional deficit pattern for mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia. METHODS: The ADFACS, the Interview for Deterioration in Daily Living Activities in Dementia (IDDD), and the Mini Mental State Examination (MMSE) were administered to 146 control subjects (CS) and 165 patients (67 MCI and 98 AD). Nonparametric tests were used to compare the diagnostic groups. Cronbach's α and correlations with the MMSE and the IDDD were calculated. Sensitivity, specificity and predictive values were studied. RESULTS: The ADFACS had a high internal consistency (α = 0.95). Three cutoff points of 1, 4, and 17 were provided to separate CS and MCI patients, MCI and mild AD patients, and mild AD and moderate AD patients, respectively. The ADFACS strongly correlated with functional (IDDD, 0.927) and cognitive (MMSE, 0.747) measures. A similar pattern of dysfunction, but in different grades, was found for the MCI and AD groups. CONCLUSION: The ADFACS is a reliable, valid, and sensitive instrument to assess functional abilities; it is useful in dementia assessment for elderly populations.

PICOGEN: experiencia de 5 años de un programa de asesoramiento genético en demencia / PICOGEN: Five years experience with a genetic counselling program for dementia

Introducción: Describimos la experiencia del Programa de Información y Consejo Genético para demencias familiares (PICOGEN) en sus 5 a˜nos de funcionamiento. Métodos: Todos los sujetos fueron asesorados por un neurólogo que seleccionó los candidatos a estudio genético según la historia familiar y el diagnóstico (enfermedad de Alzheimer [EA], degeneración lobular frontotemporal [DLFT] o enfermedad priónica). Los sujetos asintomáticos que decidieron conocer su estatus genético siguieron un protocolo estructurado de evaluación antes y después de la realización del test genético. Resultados: Ochenta y siete pacientes de 72 familias fueron candidatos a estudio genético, 20 de 72 familias presentaban historia familiar autosómica dominante de inicio precoz (HADp). En 22 se detectó una mutación patogénica (8 PSEN1, 1 PSEN2, 1 APP, 4 MAPT, 8 PRNP), 5 no descritas previamente. Todos los casos con mutación, excepto uno PSEN1 (12,5%) y 4 PRNP (50%) presentaban HADp. En 3 casos con HADp (15%) no se encontró ninguna mutación. 24 de 54 sujetos asintomáticos de familias con mutación conocida decidieron realizarse el estudio presintomático, 10 resultaron portadores. En el seguimiento de los sujetos que realizaron el estudio predictivo no se observó ninguna complicación psiquiátrica mayor. Conclusiones: En nuestra serie la HADp resultó un criterio sensible para la detección de mutaciones patogénicas en EA y DLFT, pero no en enfermedades priónicas. Un 15% de los casos HADp no presentaron alteraciones genéticas causales en estudios diagnósticos convencionales. El 43% de los sujetos en riesgo que recibieron asesoramiento genético individual realizaron el estudio presintomático. El estudio presintomático resultó seguro en este contexto (AU)

Introduction: We describe the 5 year experience of a genetic counselling program for familial dementias (the PICOGEN program). Methods: The neurologist selected the candidates for genetic testing in the screening visit based on family history and phenotype (Alzheimer disease-AD, frontotemporal lobar degeneration-FTLD, or prion disease). Asymptomatic subjects who decided to know their genetic status were evaluated within a structured protocol by the psychiatrist and psychologist prior to entering the program and followed up afterwards. Results: A total of 87 patients from 72 families were candidates for the genetic study, 20 of the 72 families had a family history of autosomal dominant early-onset dementia (ADEOD). A pathogenic mutation was found in 22 patients (8 PSEN1, 1 PSEN2, 1 APP, 4 MAPT, 8 PRNP), 5 of which had not been previously described. All positive cases, except for 1 PSEN1 (12.5%) and 4 PRNP (50%) showed ADEOD. In 3 ADEOD cases (15%) no pathogenic mutation was found. After individual genetic counselling, 24/54 asymptomatic subjects at risk decided to have the presymptomatic study, of whom 10 (42%) were carriers of the pathogenic mutation. In the follow up, no major psychiatric complication was observed. Conclusions: In our series, family history of ADEOD was a sensitive criterion for the detection of pathogenic mutations in AD and FTLD but not in prion diseases. No genetic anomalies were detected in 15% of the ADEOD cases using conventional diagnostic procedures, and 43% of presymptomatic subjects at risk who received individual genetic counselling decided to have the study. The pre-symptomatic diagnosis proved to be safe under these conditions (AU)

PICOGEN: five years experience with a genetic counselling program for dementia.

INTRODUCTION: We describe the 5 year experience of a genetic counselling program for familial dementias (the PICOGEN program). METHODS: The neurologist selected the candidates for genetic testing in the screening visit based on family history and phenotype (Alzheimer disease-AD, frontotemporal lobar degeneration-FTLD, or prion disease). Asymptomatic subjects who decided to know their genetic status were evaluated within a structured protocol by the psychiatrist and psychologist prior to entering the program and followed up afterwards. RESULTS: A total of 87 patients from 72 families were candidates for the genetic study, 20 of the 72 families had a family history of autosomal dominant early-onset dementia (ADEOD). A pathogenic mutation was found in 22 patients (8 PSEN1, 1 PSEN2, 1 APP, 4 MAPT, 8 PRNP), 5 of which had not been previously described. All positive cases, except for 1 PSEN1 (12.5%) and 4 PRNP (50%) showed ADEOD. In 3 ADEOD cases (15%) no pathogenic mutation was found. After individual genetic counselling, 24/54 asymptomatic subjects at risk decided to have the pre-symptomatic study, of whom 10 (42%) were carriers of the pathogenic mutation. In the follow up, no major psychiatric complication was observed. CONCLUSIONS: In our series, family history of ADEOD was a sensitive criterion for the detection of pathogenic mutations in AD and FTLD but not in prion diseases. No genetic anomalies were detected in 15% of the ADEOD cases using conventional diagnostic procedures, and 43% of pre-symptomatic subjects at risk who received individual genetic counselling decided to have the study. The pre-symptomatic diagnosis proved to be safe under these conditions.

Cardiac sympathetic impairment parallels nigrostriatal degeneration in Probable Dementia with Lewy Bodies.

AIM: Dementia with Lewy Bodies (DLB) must be distinguished from other types of dementia because of important differences in patient management and outcome. Both reduction in cardiac 123I-metaiodobenzilguanidine (MIBG) uptake and decreased 123I-FP-CIT binding in basal ganglia have been described in DLB. The aim of this study was to assess the relationship between cardiac sympathetic activity and nigrostriatal degeneration in patients with probable DLB. METHODS: Twenty-eight patients (15 males; mean age 77 years, range 64-88 years) with clinical international criteria of probable DLB were included in the study. All patients underwent a cardiac MIBG scintigraphy and a FP-CIT SPECT. Global cardiac MIBG uptake was semiquantified by means of heart-to-mediastinum ratio (HMR) (normal >1.56). FP-CIT binding in basal ganglia was calculated and compared with an age-matched control group. The relation between cardiac MIBG uptake and FP-CIT uptake in basal ganglia, and the relationship of these two techniques with distinctive symptoms of DLB, features of past medical history and data from the neuropsychological examination were assessed. RESULTS: Cardiac MIBG uptake was decreased in 23 of 28 patients (HMR=1.32, range 0.95-1.85). The FP-CIT binding in basal ganglia was significantly lower than in control group (2.01±0.5 vs 2.62±0.2, P<0.05). All patients with reduced cardiac HMR showed decreased FP-CIT binding in basal ganglia. There was a positive correlation between the HMR and specific binding ratio of striatum (P<0.01). A high correlation between FP-CIT SPECT and the presence of parkinsonism also was found. No correlation between cardiac MIBG uptake and demographic, clinical or neuropsychological data was found. CONCLUSION: In probable DLB cardiac MIBG uptake and FP-CIT binding in basal ganglia are reduced. The positive correlation between both measures suggests that cardiac sympathetic degeneration and nigrostriatal degeneration parallel similarly in patients with probable DLB.

Problem-solving abilities and frontal lobe cortical thickness in healthy aging and mild cognitive impairment.

Mild cognitive impairment (MCI) is considered a transitional state between normal aging and Alzheimer disease. Most MCI subjects present disturbances in multiple neuropsychological domains, including executive function. This study aimed at exploring frontal lobe cortical thinning in MCI and healthy controls, and its relationship with problem-solving abilities. Twenty-three MCI patients and 30 elderly controls underwent MRI and neuropsychological assessment. Cortical thickness was measured by means of FreeSurfer. Problem-solving was assessed by means of the Tower of London (TOL) task. MCI showed a global thinning of the cortex. With regard to specific regions of interest, a thinning in the left frontal lobe and the bilateral posterior cingulate gyri was found. Partial correlations, after controlling for age, education, Mini-Mental Status Examination, and non-frontal mean thickness revealed negative significant correlations between frontal lobe thickness and executive outcomes in the control group. This counterintuitive relationship was not observed in the MCI group, suggesting that the frontal cortical atrophy observed in MCI entails a specific pathology-related relationship with high-level executive outcomes that is qualitatively different from that observed in healthy aging.

[Prevalence of cognitive deterioration in people over 80-years-old: COGMANLLEU study]. / Prevalencia de deterioro cognitivo en personas mayores de 80 años: estudio COGMANLLEU.

INTRODUCTION: We want to detect the prevalence of cognitive prevalence deterioration in the elderly population of 80-years-old or older, their grade of deterioration and the causal pathogenic entity. DESIGN: a cross-sectional population study, including a first phase of screening and a second one of diagnosis confirmation. STUDY SUBJECTS: a total of 877 elderly people of 80-years-old or older belonging to the basic health care area of Manlleu (Osona, Catalonia midlands). In the first phase, relatives and/or caregivers were interviewed, and the participating subjects underwent a set of tests. Those who obtained 24 points or less on the Mini-Mental State Examination (MMSE) and/or an equal Global Deterioration Scale (GDS) or over 3 were admitted to the second phase. During the second phase, a general and a neurological examination were performed, along with blood tests, cranial computed tomography scan and a neuropsychological study. DSM-IV criteria were used for dementia diagnosis, NINCDS-ADRA criteria for Alzheimer's disease (AD) and NINCS-AIREN for vascular dementia. RESULTS: Half of the people over 80-years-old had cognitive deterioration. One-fourth had dementia. A total of 70.3% of these dementias corresponded to AD (47.2% AD without vascular lesions and 23.1% AD with vascular lesions) and 12% corresponded to vascular dementia. The percentage of other degenerative dementias was 17.6%. Age and gender were observed to be associated to dementia. CONCLUSIONS: The prevalence of dementia in the COGMANLLEU study is similar to other European studies. AE is the most frequent dementia.

[Genetic and environmental factors that may influence in the senile form of Alzheimer's disease: nested case control studies]. / Factores genéticos y ambientales que pueden influir en la forma senil de la enfermedad de Alzheimer: estudio de casos y controles anidado.

INTRODUCTION: We identify the genetic and environmental factors associated to Alzheimer's disease (AD) in a population aged 80 years or greater. POPULATION STUDIED: subjects who participated in the COGMANLLEU study on prevalence of cognitive deterioration in Manlleu (Osona, Central Catalonia). DESIGN: nested case control studies. The subjects who were diagnosed of AD (cases) in phases 2 of said study were paired 1:1 by age and gender with control subjects who were selected from among those who had no suspicion of cognitive deterioration and who had been examined in phase 1 of the study. The participating subjects (cases and controls) and their family or caregivers were interviewed. This included psychometric tests, physical examination, biological measurements, cranial computed tomography scan and determination of ApoE genotype. RESULTS: Age is the principal factor associated to AD: risk of getting the disease is six time greater among those over 85 years (odds ratio [OR]: 6.54; 95% confidence interval [CI]: 2.05-20.81; p<0.05). Other factors associated of AD were female gender (OR: 3.17; 95 % CI: 0.80-12.50) and having been exposed to general anesthesia (OR: 3.22; 95 % CI: 1.03-10.09; p < 0.05). Arterial hypertension (AHT) presented a negative association (OR: 0.37; 95% CI: 0.10-1.31; p<0.05). An association was also observed between AD and the presence of ApoE4 allele so that the likelihood of ApoE4 in subjects with AD was three times greater than in the control group (OR: 3.44; 95% CI: 0.67-17.62). CONCLUSIONS: The results agree with the hypothesis that senile AD is a complex, multifactorial disease in which different genetic and environmental factors play a part, among which having received general anesthesia has a role that can be considered in future research.

Prevalencia de deterioro cognitivo en personas mayores de 80 años: estudio COGMANLLEU / Prevalence of cognitive deterioration in people over 80 years old: COGMANLLEU study

Introducción. Se quiere detectar la prevalencia de deteriorocognitivo en la población de edad igual o superior a 80 años, asícomo el grado de deterioro y la entidad patológica causal.Método. Diseño: estudio transversal de base poblacional con unaprimera fase de cribado y una segunda fase de confirmación del diagnóstico.Sujetos de estudio: 877 personas de edad igual o mayor a 80años adscritas al área básica de salud de Manlleu (Osona, Cataluñacentral). En la primera fase se realizó una entrevista a familiares y/o acuidadores y se pasó una batería de tests a los sujetos participantes.Pasaron a la segunda fase los que obtuvieron una puntuación igual omenor a 24 en el Mini-Mental State Examination (MMSE) y/o una EscalaGlobal de Deterioro (GDS) igual o superior a 3. En la segunda fasese procedió a la exploración general y neurológica, a la realización deuna analítica, tomografía computerizada craneal y estudio neuropsicológico.Para el diagnóstico de demencia se utilizaron los criteriosdel DSM-IV, para la enfermedad de Alzheimer (EA) los del NINCDSADRDAy para la demencia vascular los del NINCS-AIREN.Resultados. La mitad de las personas mayores de 80 años presentabandeterioro cognitivo. Una cuarta parte presentaban demencia.El 70,3 % de las demencias correspondía a EA (47,2% EA sin lesionesvasculares y 23,2% EA con lesiones vasculares) y el 12% ademencia vascular. El porcentaje de otras demencias degenerativas ysecundarias fue del 17,6%. Se observó asociación de la demenciacon la edad y el género.Conclusiones. La prevalencia de demencia en el estudio COGMANLLEUes similar a la descrita en otros estudios europeos. La EAconstituye la demencia más frecuente (AU)

Introduction. We want to detect the prevalence of cognitiveprevalence deterioration in the elderly population of 80 years oldor older, their grade of deterioration and the causal pathogenicentity.Method. Design: a cross-sectional population study, includinga first phase of screening and a second one of diagnosisconfirmation. Study subjects: a total of 877 elderly people of 80years old or older belonging to the basic health care area of Manlleu(Osona, Catalonia midlands). In the first phase, relativesand/or caregivers were interviewed, and the participating subjectsunderwent a set of tests. Those who obtained 24 points orless on the Mini-Mental State Examination (MMSE) and/or anequal Global Deterioration Scale (GDS) or over 3 were admittedto the second phase. During the second phase, a general and aneurological examination were performed, along with bloodtests, cranial computed tomography scan and a neuropsychologicalstudy. DSM-IV criteria were used for dementia diagnosis,NINCDS-ADRA criteria for Alzheimer’s disease (AD) and NINCSAIRENfor vascular dementia.Results. Half of the people over 80 years old had cognitivedeterioration. One-fourth had dementia. A total of 70.3% of thesedementias corresponded to AD (47.2% AD without vascularlesions and 23.1% AD with vascular lesions) and 12 % correspondedto vascular dementia. The percentage of other degenerativedementias was 17.6%. Age and gender were observed to beassociated to dementia.Conclusions. The prevalence of dementia in the COGMANLLEUstudy is similar to other European studies. AE is the mostfrequent dementia (AU)

Factores genéticos y ambientales que pueden influir en la forma senil de laenfermedad de Alzheimer: estudiode casos y controles anidado / Genetic and environmental factors that may influence in the senile form of Alzheimer's disease: nested case control studies

Introducción. Se identifican los factores genéticos y ambientalesasociados a la enfermedad de Alzheimer (EA) en una población deedad igual o superior a 80 años.Método. Población estudiada: sujetos que participaron en el estudioCOGMANLLEU sobre prevalencia de deterioro cognitivo en Manlleu(Osona, Cataluña central). Diseño: estudio de casos y controles anidado.Los sujetos que fueron diagnosticados de EA (casos) en la fase 2 delmencionado estudio se emparejaron 1:1 por edad y sexo a sujetos controlque se seleccionaron entre los que no presentaron ninguna sospechade deterioro cognitivo y que habían sido examinados en la fase 1del estudio. Se realizó una entrevista a los sujetos participantes (casosy controles) y a sus familiares o cuidadores que incluyó pruebas psicométricas,exploración física, determinaciones biológicas, tomografíacomputarizada craneal y determinación del genotipo ApoE.Resultados. La edad es el principal factor asociado a la EA: elriesgo de contraer la enfermedad es seis veces superior entre los mayoresde 85 años (odds ratio [OR]: 6,54; intervalo de confianza [IC]95%: 2,05-20,81; p<0,05). Otros factores asociados a la EA fueron elsexo femenino (OR: 3,17; IC 95 %: 0,80-12,50) y haber estado expuestosa anestesia general (OR: 3,22; IC 95%: 1,03-10,09; p<0,05).La hipertensión arterial (HTA) presentaba una asociación negativa(OR: 0,37; IC 95 %: 0,10-1,31; p<0,05). También se observó asociaciónentre la EA y la presencia del alelo ApoE4 de manera que la probabilidadde ApoE4 en los sujetos con EA era tres veces superior a ladel grupo control (OR: 3,44; IC 95%: 0,67-17,62).Conclusiones. Los resultados concuerdan con la hipótesis deque la EA senil es una enfermedad compleja, multifactorial, en la queintervienen diversos factores genéticos y ambientales entre los queel recibir anestesia general puede desempeñar un papel a consideraren investigaciones futuras (AU)

Introduction. We identify the genetic and environmentalfactors associated to Alzheimer's disease (AD) in a populationaged 80 years or greater.Method. Population studied: subjects who participated in theCOGMANLLEU study on prevalence of cognitive deterioration inManlleu (Osona, Central Catalonia). Design: nested case controlstudies. The subjects who were diagnosed of AD (cases) in phases2 of said study were paired 1:1 by age and gender with controlsubjects who were selected from among those who had no suspicionof cognitive deterioration and who had been examined inphase 1 of the study. The participating subjects (cases and controls)and their family or caregivers were interviewed. This includedpsychometric tests, physical examination, biological measurements,cranial computed tomography scan and determinationof ApoE genotype.Results. Age is the principal factor associated to AD: risk ofgetting the disease is six time greater among those over 85 years(odds ratio [OR]: 6.54; 95% confidence in-terval [CI]: 2.05-20.81;p<0.05). Other factors associated of AD were female gender (OR:3.17; 95 % CI: 0.80-12.50) and having been exposed to generalanesthesia (OR: 3.22; 95 % CI: 1.03-10.09; p < 0.05). Arterialhypertension (AHT) presented a negative association (OR: 0.37;95% CI: 0.10-1.31; p<0.05). An association was also observedbetween AD and the presence of ApoE4 allele so that the likelihoodof ApoE4 in subjects with AD was three times greater thanin the control group (OR: 3.44; 95% CI: 0.67-17.62).Conclusions. The results agree with the hypothesis that senileAD is a complex, multifactorial disease in which different geneticand environmental factors play a part, among which havingreceived general anesthesia has a role that can beconsidered in future research (AU)

Whole genome analysis in a consanguineous family with early onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is a clinically and genetically heterogeneous condition in which the typical features appear significantly earlier in life (before 65 years). Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in autosomal dominant forms of EOAD. However, in about 50% of Mendelian cases and in most of the sporadic EOAD patients, no mutations have been found. We present clinical characteristics of an Israeli family comprising two affected siblings with EOAD born to neurologically healthy parents who were first cousins (both parents died after 90 years old). Sequence analysis of PSEN1, PSEN2, APP, TAU, PGRN, and PRNP failed to reveal any mutations in the affected siblings. Because the disease in this family is consistent with an autosomal recessive mode of inheritance we identified all homozygous regions identical by descent (IBD) in both siblings, by high-density SNP genotyping. We provide here the first catalog of autozygosity in EOAD and suggest that the regions identified are excellent candidate loci for a recessive genetic lesion causing this disease.

Mild cognitive impairment: a risk indicator of later dementia, or a preclinical phase of the disease?

OBJECTIVES: The proposals for classifying the transitional range between normal, ageing-associated cognitive dysfunctions and those suggestive of evolution towards dementia do not clarify whether the profiles are risk indicators of later cognitive impairment or represent preclinical phases of dementia. METHODS: Retrospective study of the baseline neuropsychological performance of ten subjects with subjective complaints of memory loss which evolved to dementia within 2 years and who meet clinical and neurological diagnosis for Probable Alzheimer's Disease (Progression group). They were compared with 34 normal subjects (Normative group), 33 patients with subjective complaints of memory who in 2 year did not evolve towards dementia and presented a stable profile (Stable group), and 47 Alzheimer's patients (Alzheimer group). A broad neuropsychological battery was administered to assess a range of cognitive functions. RESULTS: The Progression group presented a globally poor baseline neuropsychological performance, except in Working Memory, with clear deficits in Episodic Memory and Visual Memory. In the logistic regression analysis, Delayed Verbal Memory was significant as prognostic value for 80 . 5% of cases. CONCLUSION: Deficit on Episodic and Visual Memory at least 1.5 SD below T = 50 are preclinical manifestations of dementia in subjects with complain of memory loss. The use of broad neuropsychological batteries and the quantitative assessment of deficits is essential to identify and predict the risk of dementia.

Valor diagnóstico y correlaciones funcionales de la escala ADAS-Cog en la enfermedad de Alzheimer: datos del proyecto NORMACODEM / Diagnostic value and functional correlations of the ADAS-Cog scale in Alzheimer's disease: data on NORMACODEM project

Introducción. El objetivo es estudiar la validez de criterio de la Alzheimer's Disease Assessment Scale (ADAS) y de su subescala cognitiva ADAS-Cog para el diagnóstico de la enfermedad de Alzheimer (EA) y determinar diferentes puntos de corte obteniendo la sensibilidad y especificidad diagnósticas respectivas. Además se pretenden estudiar las correlaciones de las puntuaciones de la escala ADAS con medidas funcionales.Métodos. Se estudiaron 451 sujetos (254 controles sanos,86 casos con deterioro cognitivo sin demencia y 111 sujetos afectos de EA). Se obtuvieron las puntuaciones de la escala ADAS-total. La puntuación global es la resultante de la suma de dos subtests: la subescala cognitiva (ADAS-Cog) y la subescala no cognitiva (ADAS-Nocog). Se aplicaron ajustes por edad y escolaridad correspondientes para cada sujeto. A fin de poder establecer la correlación con medidas funcionalesse administraron la Rapid Disability Rating Scale-2(RDRS-2), la Blessed Dementia Rating Scale (BDRS) y la escala Interview for Detererioration of Daily Living in Dementia (IDDD). El estudio estadístico se realizó mediante las curvas ROC y el coeficiente de correlación de Pearson. Resultados. El punto de corte más equilibrado para la ADAS-total ajustado por edad y escolaridad fue de >= 17 (sensibilidad: 90,09 %, y especificidad: 85,88%). El punto de corte más equilibrado del ADAS-Cog ajustado por edad y escolaridad fue de >= 12 (sensibilidad: 89,19 %, y especificidad: 88,53%). El área bajo la curva ROC fue, respectivamente, 0,95 y 0,94. La escala ADAS-total y ADAS-Cog presentan buenas correlaciones con las escalas funcionales estudiadas. Conclusiones. Tanto la ADAS-total como la ADAS-Cog presentan una buena validez discriminativa en términos de sensibilidad, especificidad y valor predictivo. Asimismo existe una buena correlación entre el deterioro funcional estudiado en los pacientes con EA y la puntuación obtenida en ambas escalas

Introduction. The aims of this study were to assessthe criterion validity of Alzheimer's Disease AssessmentScale (ADAS) and its cognitive subscale (ADAS-Cog) forthe diagnosis of Alzheimer’s disease (AD), and to determine their different cut-off scores and sensitivity and specificity values. In addition, we also attempted tostudy the possible correlations between cognitive scores(ADAS) and functional measures. Methods. 451 subjects were studied (254 controls, 86 subjects with mild cognitive impairment and 111 patients with AD). ADAS total score was obtained by adding the cognitive (ADAS-Cog) and non-cognitive (ADAS-Nocog) scales. Scores were adjusted for age and formal education. For assessing the possible correlation between cognitive and functional measures, the following instruments were administered: Rapid Disability Rating Scale-2 (RDRS-2), Blessed Dementia Rating Scale (BDRS) and the Interview for the Deterioration of Daily Living in Dementia (IDDD). Statistical analysis: ROC curves and Pearson correlation coefficient. Results. ADAS best cut-off score for dementia was >=17 providing sensitivity and specificity values of 90.09% and 85.88 % respectively, while for the ADAS-Cog best cut-off score was >= 12 with sensitivity and specificity values of 89.19 % and 88.53 % respectively. In both cases scores were adjusted for age and formal education. The area under the ROC curve was 0.95 and 0.94 respectively. Highly significant correlations were found for ADAS and 19 ADAS-Cog with the functional scales studied. Conclusions. Both, ADAS and ADAS-Cog report good validity in terms of sensitivity, specificity and as predictive value for AD. Moreover, significant correlations were found between the functional impairment observed in patients with AD and the overall scores achieved in the ADAS and ADAS-Cog

[Diagnostic value and functional correlations of the ADAS-Cog scale in Alzheimer's disease: data on NORMACODEM project]. / Valor diagnóstico y correlaciones funcionales de la escala ADAS-Cog en la enfermedad de Alzheimer: datos del proyecto NORMACODEM.

INTRODUCTION: The aims of this study were to assess the criterion validity of Alzheimer's Disease Assessment Scale (ADAS) and its cognitive subscale (ADAS-Cog) for the diagnosis of Alzheimer's disease (AD), and to determine their different cut-off scores and sensitivity and specificity values. In addition, we also attempted to study the possible correlations between cognitive scores (ADAS) and functional measures. METHODS: 451 subjects were studied (254 controls, 86 subjects with mild cognitive impairment and 111 patients with AD). ADAS total score was obtained by adding the cognitive (ADAS-Cog) and non-cognitive (ADAS-Nocog) scales. Scores were adjusted for age and formal education. For assessing the possible correlation between cognitive and functional measures, the following instruments were administered: Rapid Disability Rating Scale-2 (RDRS-2), Blessed Dementia Rating Scale (BDRS) and the Interview for the Deterioration of Daily Living in Dementia (IDDD). STATISTICAL ANALYSIS: ROC curves and Pearson correlation coefficient. RESULTS: ADAS best cut-off score for dementia was > or = 17 providing sensitivity and specificity values of 90.09% and 85.88 % respectively, while for the ADAS-Cog best cut-off score was > or = 12 with sensitivity and specificity values of 89.19 % and 88.53 % respectively. In both cases scores were adjusted for age and formal education. The area under the ROC curve was 0.95 and 0.94 respectively. Highly significant correlations were found for ADAS and 19 ADAS-Cog with the functional scales studied. CONCLUSIONS: Both, ADAS and ADAS-Cog report good validity in terms of sensitivity, specificity and as predictive value for AD. Moreover, significant correlations were found between the functional impairment observed in patients with AD and the overall scores achieved in the ADAS and ADAS-Cog.

Espectroscopia protónica en el deterioro cognitivo leve / Proton spectroscopy in mild cognitive impairment

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Estudio de la Escala de Evaluación Rápida de Discapacidad-2 (Rapid Disability Rating Scale-2) en la enfermedad de Alzheimer: datos del proyecto NORMACODEM / Rapid Disability Rating Scale-2 in Alzheimer's disease: NORMACODEM project data

Introducción. El propósito del presente artículo fue el estudio de la Rapid Disability Rating Scale-2 (RDRS-2) en la enfermedad de Alzheimer (EA). Se analiza la fiabilidad testretest, la consistencia interna, la validez discriminativa de esta escala y el grado de correlación con otras escalas funcionales y cognitivas. Material y métodos. Se estudiaron 451 sujetos: 254 controles sanos, 86 casos de deterioro cognitivo sin demencia (DSD) y 111 sujetos afectos de EA. Se obtuvieron las puntuaciones de los diversos apartados de la escala de RDRS-2. La puntuación total de la RDRS-2 es la suma resultante de tres subescalas: actividades de la vida diaria, grado de discapacidad y problemas especiales. A fin de poder establecer su correlación con otras escalas funcionales y tests cognitivos se aplicaron la Blessed Dementia Rating Scale (BDRS), Interview for Detererioration of Daily Living in Dementia (IDDD), la subescala cognitiva del Alzheimer's Disease Assessment Scale (ADASCog) y el Mini-Mental State Examination (MMSE). Estudio estadístico: regresión lineal multivariable. Validación cruzada. Curvas ROC. Coeficiente de correlación intraclase. Coeficiente alfa de Cronbach. Coeficiente de Pearson. Resultados. Las puntuaciones obtenidas de la RDRS-2 (media y DE) fueron las siguientes: controles (18,95; 1,64), DSD (20,61; 2,88) y EA (28,96; 9,07). La regresión lineal multivariable demostró que la puntuación de la RDRS-2 no está influenciada por factores socioculturales, tales como la edad o la escolaridad. Se objetivaron las siguientes correlaciones: BDRS, r=0,820; IDDD, r=0,882; ADAS-Cog, r=0,762, y MMSE, r=0,742. El coeficiente de correlación intraclase fue de 0,86 y el coeficiente alfa de Cronbach de 0,91. El punto de corte más equilibrado de la RDRS-2 fue 21 (sensibilidad: 82,88 %, y especificidad: 88,8 %). El área bajo la curva ROC fue de 0,92. Conclusiones. La presente versión en lengua castellana de la RDRS-2 no está influenciada por factores socioculturales, presenta gran fiabilidad test-retest y consistencia interna. Aunque no fue diseñada específicamente para usarla en la EA, se correlaciona de forma significativa con otras escalas funcionales y además existe una buena correlación con el grado de deterioro cognitivo presente en pacientes con EA (AU)

INTRODUCTION: The study aimed to investigate the Rapid Disability Rating Scale-2 (RDRS-2) in Alzheimer's disease (AD). Test retest reliability, internal consistency, data of discriminant validity of the scale, correlations with other functional and cognitive measures were analyzed. MATERIAL AND METHODS: 451 subjects were assessed: 254 healthy controls, 86 with cognitive impairment but no dementia (CIND) and 111 subjects diagnosed of AD. Total and subscales scores of the RDRS-2 were obtained. The total score is the sum of three subscales: activities of daily living, disability, and special problems. To establish its correlation with other functional scales and cognitive instruments, the following tools were applied: Blessed Dementia Rating Scale (BDRS), Interview for the Deterioration of Daily Living in Dementia (IDDD), Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) and the Mini-Mental State Examination (MMSE). STATISTICAL ANALYSIS: lineal multivariate regression analysis. Crossvalidation. ROC curves. Intraclass coefficient. Cronbach's alpha and Pearson's Correlation coefficient. RESULTS: RDRS-2 scores by group were the following (mean and SD): Controls (18.95; 1.64), CIND (20.61; 2.88), and AD (28.96; 9.07). Results from regression analysis 282 demonstrated absence of influence of sociocultural variables such as age and education in RDRS-2 scores. Correlations with other instruments were as following: BDRS, r=0.820; IDDD, r=0.882; ADAS-Cog, r=0.762, and MMSE, r=0.742. Intraclass coefficient was 0.86 and Cronbach's alpha was 0.91. For the RDRS-2 the best cutoff score was 21 (82.88% sensitivity and 88.8% specificity). Area under the ROC curve was 0.92. CONCLUSIONS: The Spanish adaptation of the RDRS-2 is free of sociocultural influence, and shows very adequate data on internal consistency and stability. Although not specifically designed for its use in AD it correlates highly and significantly with other functional scales as well as with the degree of cognitive impairment in AD (AU)

Estudio observacional sobre seguridad, tolerabilidad y efectividad de la galantamina en pacientes con enfermedad de Alzheimer leve a moderadamente grave / Observational study on safety, tolerability and effectiveness of galantamine in patients with mild to moderately severe Alzheimer's disease

Introducción. Ensayos clínicos controlados han demostrado la seguridad, tolerabilidad y efectividad de la galantamina en pacientes con enfermedad de Alzheimer (EA). Se presenta un estudio realizado en España, de carácter observacional y multicéntrico, con galantamina en el tratamiento de la EA leve a moderadamente grave en condiciones asistenciales reales. Métodos. Se llevaron a cabo cinco visitas durante un período de observación de 6 meses. El tratamiento con galantamina fue iniciado según la pauta estándar. Se recogieron todos los acontecimientos adversos (AA) comunicados por los pacientes, con especial atención a los considerados graves. También se exploraron las áreas cognitiva, actividades de la vida diaria, los síntomas conductuales y la calidad del sueño. Resultados. De los 723 pacientes reclutados se excluyeron 74, quedando una muestra total de 649 (71% mujeres y 29% varones). El 56.3% completó todas las visitas. La puntuación basal media del Mini-Examen Cognoscitivo (MEC) fue de 19,4 (DE: 4,7). El 29,3% de los pacientes comunicaron un total de 400 AA. Los AA más frecuentes fueron: náuseas (9,7%), vómitos (7,1), mareo (4,6%) y diarrea (4,5%). La puntuación del MEC se estabilizó a lo largo del estudio y hubo diferencias significativas favorables en la valoración de la conducta y la calidad del sueño. Conclusiones. La galantamina es un tratamiento bien tolerado en pacientes con EA leve a moderadamente grave y ha mostrado efectividad cognitiva, funcional y conductual en la práctica clínica habitual (AU)

INTRODUCTION: Several controlled clinical trials have demonstrated safety, tolerability, and efficacy of galantamine in patients with Alzheimer's disease (AD). We present an observational and multicenter study carried out in Spain. Its main objective was the assessment of the safety and tolerability of galantamine in the treatment of mild to moderately severe dementia of the Alzheimer type under real clinical conditions. METHODS: The study had five visits over a 6-month period. Titration of galantamine was performed on a standard basis. All the adverse events (AE) reported were recorded. Serious AE were particularly considered. Effectiveness was also assessed covering cognitive, functional, behavioral and sleep domains. RESULTS: 723 patients were enrolled but 74 were excluded, a sample of 649 (71% women and 29% men) remaining. A total of 56.3% patients completed all visits. Baseline Mini-Mental mean score was 19,4 (SD: 4,7). Up to 400 AEs were collected from 29.3% of the patients. The commonest AEs were: nausea (9.7%), vomiting (7.1%), dizziness (4.6%), and diarrhea (4.5%). Mini-Mental scores were stable over time and favorable and significant differences in behavioral and sleep evaluations were observed. CONCLUSIONS: Galantamine is a safe and well-tolerated treatment, and provides cognitive, functional, and behavioral benefits in patients with mild to moderately severe AD (AU)

[Rapid Disability Rating Scale-2 in Alzheimer's disease: NORMACODEM project data]. / Estudio de la Escala de Evaluación Rápida de Discapacidad-2 (Rapid Disability Rating Scale-2) en la enfermedad de Alzheimer: datos del proyecto NORMACODEM.

INTRODUCTION: The study aimed to investigate the Rapid Disability Rating Scale-2 (RDRS-2) in Alzheimer's disease (AD). Test retest reliability, internal consistency, data of discriminant validity of the scale, correlations with other functional and cognitive measures were analyzed. MATERIAL AND METHODS: 451 subjects were assessed: 254 healthy controls, 86 with cognitive impairment but no dementia (CIND) and 111 subjects diagnosed of AD. Total and subscales scores of the RDRS-2 were obtained. The total score is the sum of three subscales: activities of daily living, disability, and special problems. To establish its correlation with other functional scales and cognitive instruments, the following tools were applied: Blessed Dementia Rating Scale (BDRS), Interview for the Deterioration of Daily Living in Dementia (IDDD), Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) and the Mini-Mental State Examination (MMSE). STATISTICAL ANALYSIS: lineal multivariate regression analysis. Crossvalidation. ROC curves. Intraclass coefficient. Cronbach's alpha and Pearson's Correlation coefficient. RESULTS: RDRS-2 scores by group were the following (mean and SD): Controls (18.95; 1.64), CIND (20.61; 2.88), and AD (28.96; 9.07). Results from regression analysis 282 demonstrated absence of influence of sociocultural variables such as age and education in RDRS-2 scores. Correlations with other instruments were as following: BDRS, r=0.820; IDDD, r=0.882; ADAS-Cog, r=0.762, and MMSE, r=0.742. Intraclass coefficient was 0.86 and Cronbach's alpha was 0.91. For the RDRS-2 the best cutoff score was 21 (82.88% sensitivity and 88.8% specificity). Area under the ROC curve was 0.92. CONCLUSIONS: The Spanish adaptation of the RDRS-2 is free of sociocultural influence, and shows very adequate data on internal consistency and stability. Although not specifically designed for its use in AD it correlates highly and significantly with other functional scales as well as with the degree of cognitive impairment in AD.

[Observational study on safety, tolerability and effectiveness of galantamine in patients with mild to moderately severe Alzheimer's disease]. / Estudio observacional sobre seguridad, tolerabilidad y efectividad de la galantamina en pacientes con enfermedad de Alzheimer leve a moderadamente grave.

INTRODUCTION: Several controlled clinical trials have demonstrated safety, tolerability, and efficacy of galantamine in patients with Alzheimer's disease (AD). We present an observational and multicenter study carried out in Spain. Its main objective was the assessment of the safety and tolerability of galantamine in the treatment of mild to moderately severe dementia of the Alzheimer type under real clinical conditions. METHODS: The study had five visits over a 6-month period. Titration of galantamine was performed on a standard basis. All the adverse events (AE) reported were recorded. Serious AE were particularly considered. Effectiveness was also assessed covering cognitive, functional, behavioral and sleep domains. RESULTS: 723 patients were enrolled but 74 were excluded, a sample of 649 (71% women and 29% men) remaining. A total of 56.3% patients completed all visits. Baseline Mini-Mental mean score was 19,4 (SD: 4,7). Up to 400 AEs were collected from 29.3% of the patients. The commonest AEs were: nausea (9.7%), vomiting (7.1%), dizziness (4.6%), and diarrhea (4.5%). Mini-Mental scores were stable over time and favorable and significant differences in behavioral and sleep evaluations were observed. CONCLUSIONS: Galantamine is a safe and well-tolerated treatment, and provides cognitive, functional, and behavioral benefits in patients with mild to moderately severe AD.