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Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series., The authors would like to thank patients and controls who participated in this project. The Genome Research @ Fundacio ACE project (GR@ACE) is supported by Fundacion bancaria La Caixa, Grifols SA, Fundacio ACE, and ISCIII (Ministry of Health, Spain). They also want to thank the private sponsors who support the basic and clinical projects of our institution (Piramal AG, Laboratorios Echevarne, Araclon Biotech S.A., and Fundacio ACE). They are indebted to the Trinitat Port-Carbo legacy and her family for their support of Fundacio ACE research programs. Fundacio ACE is a participating center in the Dementia Genetics Spanish Consortium (DEGESCO). A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, and PI17/01474. Accion Estrategica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)-Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de Hacer Europa). L.M.R. is supported by Consejeria de Salud de la Junta de Andalucia (grant PI-0001/2017). Control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III (www.bancoadn.org, University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain); they were processed after standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. The present work was performed as part of the Biochemistry, Molecular Biology, and Biomedicine doctoral program of S. MorenoGrau at Universitat Autonoma de Barcelona (Barcelona, Spain).r Data collection and sharing for this project was partially funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). The ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, as well as through generous contributions from the following: AbbVie; the Alzheimer's Association; the Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research provides funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study was coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of Southern California.; r The AddNeuroMed data are from a public-private partnership supported by EFPIA companies and SMEs as part of InnoMed (Innovative Medicines in Europe), an integrated project funded by the European Union of the Sixth Framework program priority FP6-2004-LIFESCIHEALTH-5. Clinical leads responsible for data collection are Iwona K1oszewska (Lodz), Simon Lovestone (London), Patrizia Mecocci (Perugia), Hilkka Soininen (Kuopio), Magda Tsolaki (Thessaloniki), and Bruno Vellas (Toulouse). Imaging leads are Andy Simmons (London), Lars-Olad Wahlund (Stockholm), and Christian Spenger (Zurich). Bioinformatics leads are Richard Dobson (London) and Stephen Newhouse (London).r Funding support for the Alzheimer's Disease Genetics Consortium (ADGC) was provided through the NIA Division of Neuroscience (U01-AG032984).r The Mayo Clinic Alzheimer's Disease Genetic Studies, led by Dr. Nilufer Ertekin-Taner and Dr. Steven G. Younkin at the Mayo Clinic in Jacksonville, FL, used samples from the Mayo Clinic Study of Aging, the Mayo Clinic Alzheimer's Disease Research Center, and the Mayo Clinic Brain Bank. Data collection was supported through funding by NIA grants P50 AG016574, R01 AG032990, U01 AG046139, R01 AG018023, U01 AG006576, U01 AG006786, R01 AG025711, R01 AG017216, and R01 AG003949, NINDS grant R01 NS080820, the CurePSP Foundation, and support from the Mayo Foundation.r The Neocodex-Murcia study was funded by the Fundacion Alzheimur (Murcia), the Ministerio de Educacion y Ciencia (Gobierno de Espana), Corporacion Tecnologica de Andalucia, Agencia IDEA (Consejeria de Innovacion, Junta de Andalucia), the Diabetes Research Laboratory, and the Biomedical Research Foundation. University Hospital Clinico San Carlos has been supported by CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM); CIBERDEM is an ISCIII Project.r The ROS/MAP study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984 and U01AG46152, the Illinois Department of Public Health, and the Translational Genomics Research Institute.r The TGEN study was supported by Kronos Life Science Laboratories, the National Institute on Aging (Arizona Alzheimer's Disease Center grants P30 AG19610 and RO1 AG023193, the Mayo Clinic Alzheimer's Disease Center grant P50 AG16574, and the Intramural Research Program), the National Alzheimer's Coordinating Center (U01 AG016976), and the state of Arizona.r The authors thank the International Genomics of Alzheimer's Project (IGAP) for providing summary result data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i-Select chip was funded by the French National Foundation on Alzheimer's disease and related disorders. European Alzheimer's Disease Initiative (EADI) was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Universite de Lille 2, and the Lille University Hospital. GERAD was supported by the Medical Research Council (grant no. 503480), Alzheimer's Research UK (grant no. 503176), the Wellcome Trust (grant no. 082604/2/07/Z), and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant no.; 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIH/NIA grant R01 AG033193 and the NIA AG081220 and AGES contract N01-AG12100, the NHLBI grant R01 HL105756, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer's Association grant ADGC-10-196728.

Background and purpose Decreased plasma progranulin levels are a very specific marker for the diagnosis of frontotemporal lobar degeneration (FTLD) caused by mutations in the progranulin gene (GRN). A frequent neuroimaging pattern in this type of dementia is asymmetric cortical atrophy. The aim of this study was to screen for GRN-linked FTLD in cases with different cortical dementia phenotypes and asymmetric perisylvian atrophy. Methods Progranulin plasma levels were analyzed in a variety of FTLD phenotypes (n = 71), dementia of the Alzheimer type (DAT) (n = 22) and probable Lewy body dementia (n = 8), both latter groups presented with asymmetric perisylvian atrophy. A group of elderly controls (n = 29) and DAT cases with symmetric atrophy (n = 33) were also analyzed. The GRN gene was sequenced in cases with lower plasma levels. Results Four cases with clinical FTLD phenotypes and plasma levels below 70 ng/ml were found to carry different GRN mutations: M1?, C139R, a point mutation in the splice donor site of intron 3 (A89VfsX41), and a deletion in exon 9 (A303AfsX57), this latter one being a new mutation. Thirteen cases with levels between 72 and 85 ng/ml did not show pathogenic changes in the GRN gene. None of the cases with asymmetric atrophy and clinical phenotypes other than FTLD had GRN mutations. Conclusions Asymmetric perisylvian atrophy is not likely to predict progranulin-linked FTLD unless it is associated with a consistent FTLD clinical phenotype.

Degeneracion frontotemporal (DFT): La DFT es reconocible clinicamente, pero compleja, incluyendo procesos degenerativos y alteraciones histologicas diferentes. Supone entre el 10 y el 20% de todas las demencias en nuestro ambito; aparece antes de los 65 anos con cierta frecuencia. En aproximadamente una tercera parte de los casos es familiar, con herencia autosomica dominante. La DFT comunmente provoca atrofia cerebral, a menudo netamente delimitada; microscopicamente existen distintos patrones de alteracion. Clinicamente son caracteristicas las alteraciones de la conducta personal y social y de las funciones ejecutivas, mas notables que la afectacion de la memoria. En otras ocasiones cursa con afectacion inicial del lenguaje (afasia progresiva, demencia semantica) o asocia notorios trastornos motores. Destaca la asociacion de algunos casos con esclerosis lateral amiotrofica. En el manejo terapeutico caben importantes distinciones entre la enfermedad de Alzheimer (EA) y la DFT. Demencia con cuerpos de Lewy (DCL): Supone algo menos del 20% del total de las demencias en nuestro entorno; es algo mas frecuente que la DFT y mas propia de edades avanzadas. Debe su nombre a la presencia constante en la corteza cerebral de cuerpos de Lewy, hallazgo anatomopatologico diagnostico de enfermedad de Parkinson cuando se presenta en la sustancia negra. Siempre coexisten en grado variable alteraciones histologicas propias de la EA. Clinicamente se distinque de la EA por tener una progresion fluctuante, a menudo rapida, su asociacion con parkinsonismo y la alta frecuencia de alucinaciones visuales. El delirio y los rasgos frontales tambien pueden ser muy notorios. En la terapeutica los anticolinesterasicos pueden mejorar notablemente los sintomas y los neurolepticos empeorarlos gravemente. Los antiparkinsonianos son de utilidad limitada.

Introduction: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. Development: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 minutes. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. Conclusion: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI.The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce—but never substitute—clinical judgement, patient–doctor communication, and inter-professional dialogue. Resumen: Introducción: Los test cognitivos breves (TCB) pueden ayudar a detectar el deterioro cognitivo (DC) en el ámbito asistencial. Se han desarrollado y/o validado varios TCB en nuestro país, pero no existen recomendaciones específicas para su uso. Desarrollo: Revisión de estudios sobre el rendimiento diagnóstico en la detección del DC llevados a cabo en España con TCB que requieran menos de 20 min y recomendaciones de uso consensuadas por expertos, sobre la base de las características de los TCB y de los estudios disponibles. Conclusión: El Fototest, el Memory Impairment Screen (MIS) y el Mini-Mental State Examination (MMSE) son las opciones más recomendables para el primer nivel asistencial, pudiendo añadirse otros test (Test del Reloj [TR] y test de fluidez verbal [TFV]) en caso de resultado negativo y queja o sospecha persistente (aproximación escalonada). En el segundo nivel asistencial es conveniente una evaluación sistemática de las distintas áreas cognitivas, que puede llevarse a cabo con instrumentos como el Montreal Cognitive Assessment, el MMSE, el Rowland Universal Dementia Assessment o el Addenbrooke's Cognitive Examination, o bien mediante el uso escalonado o combinado de herramientas más simples (TR, TFV, Fototest, MIS, Test de Alteración de la Memoria y Eurotest). El uso asociado de cuestionarios cumplimentados por un informador (CCI) aporta valor añadido a los TCB en la detección del DC.La elección de los instrumentos vendrá condicionada por las características del paciente, la experiencia del clínico y el tiempo disponible. Los TCB y los CCI deben reforzar —pero nunca suplantar— el juicio clínico, la comunicación con el paciente y el diálogo interprofesional. Keywords: Brief cognitive tests, Cognitive impairment, Detection, Screening, Primary care, Specialised care, Palabras clave: Test cognitivos breves, Deterioro cognitivo, Detección, Cribado, Atención primaria, Atención especializada

Resumen: Introducción: Los test cognitivos breves (TCB) pueden ayudar a detectar el deterioro cognitivo (DC) en el ámbito asistencial. Se han desarrollado y/o validado varios TCB en nuestro país, pero no existen recomendaciones específicas para su uso. Desarrollo: Revisión de estudios sobre el rendimiento diagnóstico en la detección del DC llevados a cabo en España con TCB que requieran menos de 20 min y recomendaciones de uso consensuadas por expertos, sobre la base de las características de los TCB y de los estudios disponibles. Conclusión: El Fototest, el Memory Impairment Screen (MIS) y el Mini-Mental State Examination (MMSE) son las opciones más recomendables para el primer nivel asistencial, pudiendo añadirse otros test (Test del Reloj [TR] y test de fluidez verbal [TFV]) en caso de resultado negativo y queja o sospecha persistente (aproximación escalonada). En el segundo nivel asistencial es conveniente una evaluación sistemática de las distintas áreas cognitivas, que puede llevarse a cabo con instrumentos como el Montreal Cognitive Assessment, el MMSE, el Rowland Universal Dementia Assessment o el Addenbrooke's Cognitive Examination, o bien mediante el uso escalonado o combinado de herramientas más simples (TR, TFV, Fototest, MIS, Test de Alteración de la Memoria y Eurotest). El uso asociado de cuestionarios cumplimentados por un informador (CCI) aporta valor añadido a los TCB en la detección del DC.La elección de los instrumentos vendrá condicionada por las características del paciente, la experiencia del clínico y el tiempo disponible. Los TCB y los CCI deben reforzar —pero nunca suplantar— el juicio clínico, la comunicación con el paciente y el diálogo interprofesional. Abstract: Introduction: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. Development: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. Conclusion: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI.The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce — but never substitute — clinical judgment, patient-doctor communication, and inter-professional dialogue. Palabras clave: Test cognitivos breves, Deterioro cognitivo, Detección, Cribado, Atención primaria, Atención especializada, Keywords: Brief cognitive tests, Cognitive impairment, Detection, Screening, Primary care, Specialised care

Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use.Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results.The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue.

The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Background and Purpose— To provide further insight into the MRI assessment of age-related white matter changes (ARWMCs) with visual rating scales, 3 raters with different levels of experience tested the interrater agreement and comparability of 3 widely used rating scales in a cross-sectional and follow-up setting. Furthermore, the correlation between visual ratings and quantitative volumetric measurement was assessed. Methods— Three raters from different sites using 3 established rating scales (Manolio, Fazekas and Schmidt, Scheltens) evaluated 74 baseline and follow-up scans from 5 European centers. One investigator also rated baseline scans in a set of 255 participants of the Austrian Stroke Prevention Study (ASPS) and measured the volume of ARWMCs. Results— The interrater agreement for the baseline investigation was fair to good for all scales (κ values, 0.59 to 0.78). On the follow-up scans, all 3 raters depicted significant ARWMC progression; however, the direct interrater agreement for this task was poor (κ, 0.19 to 0.39). Comparison of the interrater reliability between the 3 scales revealed a statistical significant difference between the scale of Manolio and that of Fazekas and Schmidt for the baseline investigation ( z value, −2.9676; P =0.003), demonstrating better interrater agreement for the Fazekas and Schmidt scale. The rating results obtained with all 3 scales were highly correlated with each other (Spearman rank correlation, 0.712 to 0.806; P ≤0.01), and there was significant agreement between all 3 visual rating scales and the quantitative volumetric measurement of ARWMC (Kendall W , 0.37, 0.48, and 0.57; P Conclusions— Our data demonstrate that the 3 rating scales studied reflect the actual volume of ARWMCs well. The 2 scales that provide more detailed information on ARWMCs seemed preferential compared with the 1 that yields more global information. The visual assessment of ARWMC progression remains problematic and may require modifications or extensions of existing rating scales.

ObjetivoEstimar la proporción de casos de demencia detectados en personas mayores de 70 años que residen en sus domicilios y describir la utilización de los servicios sanitarios y sociales que hacen las personas con demencia.Material y métodosEncuesta poblacional de los supervivientes de la cohorte «Envejecer en Leganés» iniciada en 1993. En el tercer seguimiento de 1999–2000 se incorporó el diagnóstico clínico de la demencia realizado según el examen neurológico y una extensa batería neuropsicológica. Se preguntó también sobre la utilización de servicios sanitarios y sociales y sobre diagnósticos previos.ResultadosEn la muestra de supervivientes (n=527), la prevalencia de demencia fue de 12,1%. Sólo el 30% de los dementes había sido previamente diagnosticado por los servicios sanitarios. La proporción de demencia no detectada está significativamente asociada con su gravedad (leve, 95%; moderada, 69%; grave, 36%). Comparados con las personas mayores no dementes, los dementes utilizan con mayor frecuencia los servicios hospitalarios, la consulta médica y de enfermería a domicilio y la consulta por terceros, y con menos frecuencia, los servicios preventivos y de rehabilitación. Esta tendencia se acentúa en los pacientes con demencia grave. La utilización de los servicios sociales comunitarios es muy baja (inferior al 8% en los casos más graves).ConclusionesLa detección de la demencia en los ancianos es muy baja y deben incrementarse los esfuerzos de detección en la atención primaria. También deben aumentar los recursos sociosanitarios específicos para esta población y cambiar las pautas asistenciales del equipo de atención primaria y de los profesionales sanitarios en general.ObjectivesTo calculate the proportion of cases of dementia detected in people over 70 living in their homes and to describe the use made by people with dementia of the health and social services.Material and methodsPopulation survey of the survivors of the cohort «Growing old in Leganés», started in 1993. In the third monitoring (1999–2000), the clinical diagnosis of dementia on the basis of a neurological examination and an extensive neuro-psychological battery was included. Their use of health and social services and prior diagnoses were also asked.ResultsIn the sample of survivors (n=527), there was 12.1% prevalence of dementia. Only 30% of the demented had previously been diagnosed by the health services. The proportion of undetected dementia was significantly associated with its seriousness (light 95%, moderate 69%, severe 36%). Compared with older persons who were not demented, the demented used more often hospital services, medical and nursing consultations at home and consultations through third parties; and less often, preventive and rehabilitation services. This trend was accentuated in patients with grave dementia. The use of community social services was very low (below 8% in the most serious cases).ConclusionsThe detection of dementia in the elderly is very low and efforts to detect it in primary care need to be stepped up. Specific social-health resources for this population also need to be increased and the attendance guide-lines for primary care teams, and for health professionals in general, need to be changed.

The purpose of the present study was to compare serum levels of coenzyme Q(10) (CoQ(10)) and the coenzyme Q(10) cholesterol (CoQ(10)/cholesterol) ratio in 18 patients with Lewy body disease (LBD) with 20 matched controls. The mean serum coenzyme Q10 levels in patients with LBD were significantly reduced with respect to control group, however, no differences were found in CoQ(10)/cholesterol ratio between LBD patients and control group. There was no correlation among CoQ(10) and CoQ(10)/cholesterol ratio with age, age of onset, body mass index, duration of the disease or scores of the Mini Mental State Examination, UPDRS and Hoehn and Yahr stage. These results suggest the involvement of this enzimatic system in the pathogenic mechanism of LBD.

Proton magnetic resonance spectroscopy (1H-MRS) provides a non-invasive, in vivo insight into the brain metabolism, and has been successfully used in several neurological conditions. Our objective was to characterise the cerebral metabolic changes in dementia with Lewy bodies (DLB) patients using 1H-MRS. Single Voxel 1H-MRS was performed in 12 DLB patients with mild to moderate symptoms and 11 age-matched healthy controls. Volumes of interest (VOI) were selected, including white matter (WM) in the centrum semiovale and grey matter (GM) in the parasagittal parietal cortex. Main metabolic peaks corresponding to N-acetylaspartate (NAA), glutamate/glutamine (Glx), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were identified. These areas were measured and referred to that of the water. Metabolic ratios among the different peak areas were also calculated. In comparison with the control group, DLB patients showed significantly lower mean NAA/Cr, Glx1/Cr and Cho/Cr ratios in the WM, while their Ins/Cr and Ins/NAA ratios did not differ from those of the control group. In the GM, no significant differences were found between both groups. Correlations between age at onset, disease duration, Mini-Mental State Examination, the motor section of the Unified Parkinson’s Disease Rating Scale, Hoehn and Yahr staging and metabolic ratios, both for WM and GM, were not significant in DLB patients. Our spectroscopy data show WM involvement, along with GM preservation, in DLB patients with early or intermediate stages. Hence, 1H-MRS may provide adjunctive information in the ante-mortem diagnosis of DLB.

Objective To develop and assess the consistency and validity of simple cognitive function measures for an elderly population with low levels of formal education for use in a longitudinal study of dementia. Methods Data were from the population longitudinal study ‘Growing old in Leganes’ (Spain). In 1993, a random sample of 1540 people over 65 was drawn from the City Roll of Leganes from which 1284 (83%) were successfully interviewed. Measures of memory and orientation were based on the SPMSQ (Short Portable Mental Status Questionnaire), the Barcelona test and the short story from EPESE (Established Populations Epidemiologic Studies of the Elderly). Non-response to a test item was coded as an error. Internal consistency was assessed by factor analysis and Cronbach's alpha. Construct validity was examined with multiple linear regressions of the proposed measurements on variables chosen from the existing literature on cognitive function. Results Two factors, memory and orientation, emerged from the factor analysis. Internal consistency of the proposed indexes for memory and orientation was acceptable. Memory and orientation scores were summed into one summary index of cognition. Associations between covariates and both cognitive indexes were in the expected direction. Among those highly functional, orientation was influenced by illiteracy due to higher error rates in the time orientation items based on dates; however, memory and summary scores were not significantly different by literacy status. A large proportion of the variance in IADL was explained by the memory and orientation measures. Conclusion The memory and orientation indexes are valid and reliable measurements of cognitive function for use in a population of community dwelling elderly with low levels of formal education and high rates of illiteracy. Copyright © 2000 John Wiley & Sons, Ltd.

Vascular dementia (VaD) is a heterogeneous pathology currently regarded as the result of a variety of causes. Different types of VaD can be identified according to different criteria. This heterogeneity might be one of the causes of the controversial results observed, up to now, in clinical trials. Recently, the 10th revision of the International Classification of Diseases (ICD-10) explicitly identified subcortical VaD as a welldefined subgroup. Abnormalities of white matter are clearly detectable with computed tomography or magnetic resonance scans. The clinicoradiological association of dementia, blood hypertension, and other vascular risk factors, extensive white matter lesions, and small subcortical infarcts might be considered as a clinical univocal entity. Following the encouraging results of a preliminary pilot study, the above-mentioned criteria were followed to define a population of patients to be enrolled in a double-blind, parallel- groups, placebo-controlled clinical trial with nimodipine, which has been proposed as a drug that can improve cognitive functions in patients with VaD. The paper discusses the protocol design of this ongoing trial and its main entry criteria, with particular emphasis on the definition of the population to be enrolled. Implication for future trials in subcortical VaD are discussed further.

White matter changes (WMC), detected by imaging techniques, are frequent in stroke patients. The aim of the study was to determine how WMC relate to stroke subtypes and to stroke outcome. We made a systematic Medline search for articles appearing with two of the following key words: either ‘WMC or white matter lesions or leukoencephalopathy or leukoaraiosis’ and ‘stroke or cerebral infarct or cerebral hemorrhage or cerebrovascular disease or transient ischemic attack (TIA)’. WMC, as defined radiologically, are present in up to 44% of patients with stroke or TIA and in 50% of patients with vascular dementia. WMC are more frequent in patients with lacunar infarcts, deep intracerebral hemorrhages, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and cerebral amyloid angiopathy. After an acute ischemic stroke, WMC are associated with a higher risk of death or dependency, recurrent stroke of any type, cerebral bleeding under anticoagulation, myocardial infarction, and poststroke dementia. WMC in stroke patients are often associated with small-vessel disease and lead to a higher risk of death, and poor cardiac and neurological outcome. However, several questions remain open and need further investigations.

Since the recognition of white matter changes on CT (leukoaraiosis), rating scales for the location and severity of white matter changes have been developed, mainly for research purposes, to investigate factors such as the relation with cognition, risk factors, and pathology. The main purpose of rating scales is to provide scores that can be used in statistical analyses. The development of the NINDS-AIREN criteria for vascular dementia have introduced a new application for these rating scales in investigating and delineating the amount of white matter changes on CT/MRI sufficient to fulfill the criteria. Furthermore, in Alzheimer’s disease, recognition of white matter changes may serve to delineate homogeneous groups and help to identify patients with different symptomatology. We reviewed the existing rating scales for CT and MRI and judged their properties and reliability. The ideal rating scale does not yet exist, but different rating scales may serve different purposes, for which some recommendations are made.

This study was devised to check the feasibility and validity of a rating scale specifically designed to evaluate gait impairment in Parkinson's disease (RSGE). Demographic data, a brief questionnaire on general aspects influencing gait and mobility, a battery of scales (Barthel Index; Hoehn and Yahr staging; and Northwestern University Disability, Schwab and England, and Unified Parkinson's Disease Rating Scale [UPDRS]), and timed tests ("Up and Go" and "Steps x Seconds" tests) were recorded under protocol, as was the RSGE-Version 1.0 (23 items in four subscales). Fifty patients enrolled at two centers were included. Twenty-five (50%) were simultaneously (though independently) evaluated by three examiners, in order to determine the interrater reliability. The mean age of the patients was 67.6 +/- 11.16 years, with a mean 8.18 +/- 5.58 years of disease duration. Motor fluctuations were present in 48% of patients. The RSGE Cronbach's alpha was 0.94. Only the item "Dyskinesias" was not correlated with the RSGE total sum. The item "Axial rigidity" showed a fair interrater reliability (kappa = 0.30). However, most of the RSGE items (16/23, 70%) had kappaor = 0.65. The convergent validity with the applied scales was very high (Spearman r = 0.74-0.90, p0.001). The highest correlation (0.90) was obtained with the UPDRS. Also, the RSGE correlation with timed tests was very satisfactory ("Up and Go" = 0.81; "Steps x Seconds" = 0.70; both, p0.001). Factor analysis of the RSGE disclosed four dimensions explaining 68% of the variance. The RSGE-Version 1.0 proved to be a valid instrument. The reliability of some items has to be improved, however.

Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD) brains. Both patients and mouse models of AD show decreased level of circulating IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma IGF-I. Importantly, in presymptomatic AD mice this reduction is already manifested as a decreased brain input of serum IGF-I in response to environmental enrichment. To explore a potential diagnostic use of this early loss of IGF-I input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice. Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD mice showed blunted ECG responses. Because nonhuman primates showed identically enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD patients., This work has been supported by grants from the Spanish Ministry of Economy (Explora Program and SAF2010/17036 to IT-A and BFU2012/36107 to AN). Ángel Trueba-Sáiz holds an FPU fellowship of the Spanish Ministry of Education (ref. FPU AP2009-0372).

Several therapeutic trials have been performed for vascular dementia, with drugs differing in type and mechanism of action. The results have been almost invariably inconclusive. Given the current notion that there are different subtypes of vascular dementia according to pathophysiological mechanisms, it is reasonable to suspect that one of the main causes of the disappointing results was that the study samples included patients not fitting with the rationale of selective treatments. Testing this hypothesis is difficult because characterization of patients in relation to different subtypes of vascular dementia is not available for most studies. However, attempts are ongoing to reclassify patients entered in some trials for post hoc subgroup analyses with some preliminary interesting results. We propose that (1) specific subtypes of vascular dementia should be the target in any single trial using a treatment with a proper rationale; and (2) subcortical vascular dementia, caused by small vessel disease leading to lacunar infarcts and subcortical white matter changes, represents a clinically and radiologically well-defined entity to be considered for future trials designed specifically for testing adequate drugs.

The "cognitive reserve" hypothesis states that education provides a better tolerance to brain pathological processes. Consequently, the development of dementia would require more cognitive loss in more educated people. We examine in a cohort of patients with different levels of cognitive impairment, the relationship between the amount of cognitive loss and educational attainment.A total of consecutive outpatients were assessed prospectively with an extensive clinical and neuropsychological protocol, followed up for 6 months, diagnosed by a central expert committee as demented (DSM-III-R criteria) or cognitively impaired. They were included in the Spanish Multicentric Registry of Incident Cases of Dementia. Premorbid verbal fluency (pVF), as a marker of previous cognitive function, was estimated by a validated predictive model. Cognitive loss was defined as the difference between estimated pVF and present observed verbal fluency (oVF) in two ways: as an absolute Z-score (pVF-oVF/sigma of residuals in the normative sample) and as a relative quotient-score (pVF-oVF/pVF).A two-way ANOVA showed that clinical stage (Z-scores: F=75.88; p0.0001; quotient-scores: F=126.56; p0.0001) and also education (Z-scores: F = 83.51; p=0.0001; quotient-scores: F=34.88; p=0.0001) were positively related with both estimates of cognitive loss.Our data confirm that education, or some other related factor, determines the amount of cognitive loss needed for clinical expression of the pathological illness and gives the individuals more tolerance to these processes.

Objective: To determine whether individuals with Alzheimer's disease (AD) and the K variant allele of butyrylcholinesterase have a slower rate of cognitive decline than those without the K variant allele of butyrylcholinesterase. Method: The cognitive status of 339 community based subjects with AD was assessed with the Mini Mental State Examination at baseline and yearly over a three year follow up period. The rates of cognitive decline of subjects with and without the K variant allele were compared. Result: Presence of the K allele was associated with a slower average rate of cognitive decline in subjects with severe AD. Conclusions: This finding is consistent with the suggestion that the K variant of butyrylcholinesterase has an important role in disease progression in AD, and this may have implications for treatment.

Objective: To evaluate the efficacy of a cognitive-motor program in patients with early Alzheimer disease (AD) who are treated with a cholinesterase inhibitor (ChEI).Methods: Patients with mild cognitive impairment (MCI) (12), mild AD (48), and moderate AD (24) (Global Deterioration Scale stages 3, 4, and 5) were randomized to receive psychosocial support plus cognitive-motor intervention (experimental group) or psychosocial support alone (control group). Cognitive-motor intervention (CMI) consisted of a 1-year structured program of 103 sessions of cognitive exercises, plus social and psychomotor activities. The primary efficacy measure was the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary efficacy measures were the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Geriatric Depression Scale. Evaluations were conducted at 1, 3, 6, and 12 months by blinded evaluators.Results: Patients in the CMI group maintained cognitive status at month 6, whereas patients in the control group had significantly declined at that time. Cognitive response was higher in the patients with fewer years of formal education. In addition, more patients in the experimental group maintained or improved their affective status at month 12 (experimental group, 75%; control group, 47%; p = 0.017).Conclusions: A long-term CMI in ChEI-treated early Alzheimer disease patients produced additional mood and cognitive benefits.

To standardize the Spanish version of the 7 Minute screening neurocognitive battery (7MS) in a population sample of elderly over 70 years.We examined 416 persons, living at home, participating in elderly the longitudinal study "Aging in Leganes", aged 71 to 99 years old (mean age: 79 +- 9.2 years; 51.7 % women; 10.6 illiterate, 25 % without formal education). In order to do so, we used an extensive clinical survey, general and neurological exam and extensive neuropsychological battery with several cognitive scales, attention, language, memory, visuomotor skill and reasoning tests, Jorm's IQCODE questionnaire, CES-D depression questionnaire and the 7MS including the Benton Orientation Test, Clock Drawing Test, Free and Cued Learning Test and Categorial Verbal Fluency. Dementia was diagnosed according to DSM-IV criteria but independently of the 7MS scores. Several methods to obtain the total score of the 7MS were analyzed and the normative parameters of the test were obtained in the subgroup of non-demented subjects.The easiest and most efficient method to obtain the total score of the 7MS was the sum of the z-scores of the four subtests. We present the mean values, -1 and -1.5 standard deviations, range and percentiles of the partial and total scores of the 7MS stratified by age (71-75, 76-80, 81-85 andor = 86 years) and education (less than primary education and primary education or greater) in the subgroup of non-demented subjects.The normative data of the 7MS obtained in a representative sample of the general elderly population support its rigorous use in the Spanish clinical setting.

A heart transplant is the only effective therapeutic option open to many patients with severe heart failure and performing such an intervention is not free of complications. Little is known about the risk factors for neurological complications after a heart transplant.The aim of this study was to identify the risk factors for neurological complications following a heart transplant and, more especially, those associated with epileptic seizures, encephalopathy, cerebrovascular accidents (CVA) and headaches.We conducted a retrospective review of the records of 205 orthotopic heart transplant patients and collected clinical, haemodynamic and laboratory data before, during and after the intervention, using a standardised protocol.95 patients (48%) presented neurological complications. Their frequencies were as follows: encephalopathy (16.6%), epileptic seizures (13.6%), neuromuscular disorders (10.6%), headaches (10.6%), CVA (10.1%), psychiatric disorders (2.2%) and infection of the central nervous system (2.2%). The risk factors for encephalopathy were post-transplant renal failure (RR: 4.6; CI 95%: 1.4-15), post-transplant hepatic failure (RR: 5.6; CI 95%: 1.5-22) and pre-transplant haemodynamic instability (RR: 4.3; CI 95%: 1.3-14); for epileptic seizures they were a cardiac index ofor = 2 L/min/m2 (RR: 23.8; CI 95%: 2-247) and extracorporeal circulation timeor = 115 min (RR: 11.3; CI 95%: 1-79); and for CVA the risk factor was post-transplant hepatic failure (RR: 12.9; CI 95%: 2.5-66).Neurological complications often occur after a transplant and are transient. Perioperative haemodynamic instability giving rise to cerebral ischemia and the metabolic disorders secondary to multiple organ failure are determining factors of encephalopathy, epileptic seizures and CVA.

OBJECTIVES: To calculate the proportion of cases of dementia detected in people over 70 living in their homes and to describe the use made by people with dementia of the health and social services. MATERIAL AND METHODS: Population survey of the survivors of the cohort «Growing old in Leganés», started in 1993. In the third monitoring (1999–2000), the clinical diagnosis of dementia on the basis of a neurological examination and an extensive neuro-psychological battery was included. Their use of health and social services and prior diagnoses were also asked. RESULTS: In the sample of survivors (n = 527), there was 12.1% prevalence of dementia. Only 30% of the demented had previously been diagnosed by the health services. The proportion of undetected dementia was significantly associated with its seriousness (light 95%, moderate 69%, severe 36%). Compared with older persons who were not demented, the demented used more often hospital services, medical and nursing consultations at home and consultations through third parties; and less often, preventive and rehabilitation services. This trend was accentuated in patients with grave dementia. The use of community social services was very low (below 8% in the most serious cases). CONCLUSIONS: The detection of dementia in the elderly is very low and efforts to detect it in primary care need to be stepped up. Specific social-health resources for this population also need to be increased and the attendance guide-lines for primary care teams, and for health professionals in general, need to be changed.

Dementia with Lewy bodies is a generative brain disease of unknown origin, characterised clinically by progressive mental deterioration, with striking fluctuations and transitory episodes of confusion, hallucinations and psychotic symptoms (hallucinations and paranoid deliria), extrapyramidal signs and hypersensitivity to neuroleptic drugs. The main pathological finding was the abundance of Lewy bodies in the neurons of the cortex, brain stem and other subcortical nuclei. In many cases, however, varying amounts of Alzheimer like degenerative lesions are associated.This study analyses the anatomopathological, clinical, diagnostic and therapeutic aspects of this disease.

The presence of alterations in the neuroimaging in patients with anosmia without traumatic antecedents is not frequent.Male aged 38 who came to surgery after having suffered, 6 months earlier, for 1 week, a picture of intense, oppressive holocranial headache, accompanied by fever. Associated with this, an acute complete anosmia also began and persisted up to the moment the patient came for consultation. It was not associated with any infection of the respiratory tract, there was no history of cranial trauma, no ingestion of medicines nor toxins, nor had he been exposed to toxic products. The exploration to which he was submitted only showed an anosmia and was otherwise found to be normal. Cranial MRI showed signal alterations in both lower (orbitary) convolutions of the frontal lobes, in the anterior region of the right temporal lobe and in both olfactory nerves. Tests for HIV serology, parotiditis, hepatitis B and C virus, HSV, VZV, Mycoplasma pneumoniae and lues were negative. The acute onset of the anosmia in midst of a picture of febricula and headaches made us suspect the presence of an infectious aetiology, and the alterations found in the neuroimaging could be due to post encephalic lesions, with a special predilection for olfactory areas.1. MRI plays a fundamental role in the topographic and aetiological evaluation of olfactory dysfunctions of a central origin; 2. Affectation of the central olfactory passages of an infectious aetiology in a non HIV patient and with neuroimaging findings is a rare complication.

This study was designed to assess the effects of rivastigmine (Exelon®) on the cognitive functioning of patients suffering from dementia with Lewy bodies. This was a prospective, multi-centre, randomised, double-blind, placebo-controlled exploratory study conducted at sites in the UK, Spain and Italy. The treatment period was 20 weeks with a 3-week posttreatment follow-up. The primary outcome measures were the Cognitive Drug Research (CDR) computerised assessment system and the Neuropsychiatric Inventory. Testing was conducted prior to dosing and then again at weeks 12, 20 and 23. Analysis of the data from the 92 patients who completed the study identified a significant pattern of benefits of rivastigmine over placebo on the CDR system. These benefits were seen on tests of attention, working memory and episodic secondary memory. Taking attention for example, patients given placebo showed a significant deterioration from predosing scores at 12 and 20 weeks, whereas patients on rivastigmine performed significantly above their predosing levels. These effects were also large in magnitude, the decline under placebo at week 12 being 19%, while the improvement under rivastigmine was 23%. The clinical relevance of this 23% improvement was that it took the patients 33% towards being normal for their age on this assessment of attention. These benefits to cognitive function were accompanied by a significant improvement of the other primary outcome measure, the Neuropsychiatric Inventory. Three weeks after discontinuation of rivastigmine, most parameters of cognitive performance returned to predrug levels.

The most widely accepted criteria for Alzheimer's disease (AD) diagnosis (NINCDS-ADRDA and DSM-IV) do not allow to differentiate accurately between AD and other degenerative dementias which have recently formulated criteria for its clinical diagnosis. Therefore, it is necessary to bring AD diagnostic criteria up to date in order to optimise their specificity, by assessing its most specific clinical manifestations, its most representative markers and those features typical of other diseases which are usually taken into account for a differential diagnosis. According to the latest reports on the subject, the disturbances suffered by memory, behaviour and the rest of cognitive and executive functions must be equally considered when establishing the syndromic diagnosis of dementia; this will always require the coexistence of an evident functional impairment. Due to this, the concepts of "dementia" and "mild cognitive impairment" should be clearly distinguished. For the time being, AD can only be diagnosed when dementia has been proved and this shows a series of cognitive, behavioural and neurological features which are representative of it. Nevertheless, some diagnostic markers appear to be precocious and specific enough to try to identify those patients who suffer from mild cognitive impairment due to an incipient stage of AD. We are suggesting some criteria for the clinical diagnosis of dementia, mild cognitive impairment and AD that seem to be more detail

This is a document prepared by the Spanish Society of Neurology (SEN), which was given to the President of Spain (Mr. José María Aznar) last September with the main aim of examining the current situation of Neurology in our country. It analyses the present and future of Neurology in clinical assistance, teaching and research. To prepare this document the criteria of patients' associations has been considered, including the Declaration of Madrid which has been subscribed by thirty of these associations. In spite of its relevant development in the previous decades, the current situation of Neurology in Spain is far from the ideal. To reach the recommendable menber of 3 or 4 neurologists per 100,000 inhabitants it is necessary to duplicate the present number of neurologists which has been estimated around 2/100,000; this situation is especially urgent in some Autonomous Communities. The most important problems in neurological assistance are: inadequate follow-up of the chronic outpatients, low numbers of neurological beds and of duties of Neurology, as well as of neurological case of patients with urgent neurological disorders. It is also necessary to increase the number of professors of Neurology to adequately cover pregraduate teaching; again there are important differences in teaching positions among Autonomous Communities. Neurology residence should be prolonged from 4 to 5 years. Finally, it is necessary to support the appearance of superespecialised units and to promote a coordinated research with other close specialities including basic neuroscience.

The objectives of this study were to examine the clinical and pathologic features of two subgroups of patients with dementia with Lewy bodies (DLB) differing in Alzheimer disease (AD)-type pathology load and to identify clinical variables useful in the differential diagnosis from AD. The records of 64 consecutive demented patients were reviewed. Pathologic diagnoses were independently established [35 AD cases, 11 cases of pure dementia with Lewy bodies (pDLB), and 18 cases of combined AD plus Lewy bodies (AD+LB)], and several neurodegenerative lesions were quantified. Clinical and pathologic data were compared between groups with univariate and multivariate analyses. Compared with the other groups, pDLB cases had more frequent acute-subacute onset of dementia [45% vs. AD (3%) and AD+LB (16%)], early parkinsonism [45% vs. AD (0%) and AD+LB (0%)], early [27% vs. AD (0%) and AD+LB (0%)] and late [73% vs. AD (11%) and AD+LB (16%)] hallucinations, fluctuating course [46% vs. AD (9%) and AD+LB (22%)], delusions [45% vs. AD (11%) and AD+LB (6%)], spontaneous parkinsonism [63% vs. AD (8%) and AD+LB (16%)], less frequent ideomotor apraxia and loss of insight, earlier urinary incontinence [3.2 +/- 1.4 years after onset vs. AD (6.3 years) and AD+LB (5.8 years)], shorter duration of dementia [7.7 +/- 2.4 years vs. AD (9.6 years) and AD+LB (11 years)], milder atrophy in computed tomography scans, greater brain weight, more transcortical spongiosis, wider cortex and subcortex, and less amyloid angiopathy. All pDLB cases but no AD cases had abnormal CA2 neurites. The clinical features of AD+LB patients were similar to those of AD patients other than more frequent acute-subacute onset and fluctuating evolution. Discriminant analyses selected four clinical variables differentiating pDLB from the other two groups as a whole: acute-subacute onset, early parkinsonism, early hallucinations, and early onset of urinary incontinence. Two or more of these features identified pDLB with a sensitivity of 81.8% and a specificity of 95.9%. Differentiation between the three groups (pDLB, AD+LB, and AD) or between both groups with LB (DLB) from AD could be only attained in 70% of cases. We conclude that early symptomatology is the main clue for the diagnosis of pDLB. We identified by discriminant analysis a set of clinical diagnostic criteria similar to those proposed by the Consortium on Dementia With Lewy Bodies. Accuracy was excellent for the diagnosis of pDLB but only mediocre for separating AD+LB as well as the entire DLB group from AD.

Background and Purpose —The goal of the present study was to examine a series of putative risk factors of poststroke dementia (PSD), especially those factors usually associated with cerebrovascular disease and degenerative dementia, in a series of 251 consecutive unselected stroke patients. Methods —A standard protocol was prospectively applied at admission and 3 months after stroke; this protocol included clinical, functional, and cognitive assessments, hemogram and serum biochemistry, ECG and CT exams, apolipoprotein E and angiotensin-converting enzyme genotype, and neuropsychological examination. After a neuropsychological examination and an interview with a relative, the following diagnostic criteria were used: the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV for dementia after stroke, DSM-III-R for previous dementia and dementia stage, and Association Internationale pour la Recherche et l’Enseignement en Neurologie (NINDS-AIREN) for vascular dementia. Results —Seventy-five cases (30%) demonstrated dementia at 3-month follow up; 25 of them (10%) had demonstrated dementia before the stroke. Dementia was unrelated to type (ischemic/hemorrhagic) or location of stroke, vascular factors (hypertension, diabetes, ischemic heart disease, or hypercholesterolemia), apolipoprotein E or angiotensin-converting enzyme genotype, and serum homocysteine. Age (odds ratio [OR] 1.1, 95% CI 1.03 to 1.2), previous nephropathy (OR 6.1, 95% CI 1.5 to 24.3), atrial fibrillation (OR 4.4, 95% CI 1.4 to 13.9), low Canadian Neurological Scale score at discharge (OR 0.5, 95% CI 0.4 to 0.6), and previous mental decline assessed by the shortened Spanish version of the Informant Questionnaire on Cognitive Decline in the Elderly (SS-IQCODE; OR 1.2, 95% CI 1.1 to 1.4) were the correlates of dementia in logistic regression analyses. The same risks factors were found when cases with previous dementia and with hemorrhagic stroke were excluded. Conclusions —Dementia is frequent after ischemic or hemorrhagic stroke. Age, nephropathy, atrial fibrillation, previous mental decline, and stroke severity independently contribute to the risk.

Moderate and severe primary adult hypothyroidism produces cognitive and behavioral disturbances, but the effects of mild hypothyroidism are not well established. We have tried to determine the pattern of cognitive performance and the effect of hormonal treatment in mild hypothyroidism.15 patients with subclinical or very mild hypothyroidism were compared with other 15 patients suffering from mild diseases without central nervous system damage, who were matched in age, sex and previous intelligence. A neuropsychological battery, including tests of global cognitive performance (Mini Mental Status Examination, WAIS), attention (reaction time), visual memory (Benton test, Rey's Figure), verbal memory (word learning), verbal fluency and executive functions (Trail Making Test), was applied.Hypothyroid patients had worse performance in some WAIS subtests, reaction time, verbal fluency, free recall and copy of the Rey's figure. After hormonal treatment, a significant improvement and normal performance in almost all cognitive functions were found.Even mild hypothyroidism produces cognitive defects, mainly in tasks with high attentional requirements, that can and should be corrected with hormonal replacement.

Frontotemporal dementia is a degenerative disease, usually of presenile onset, frequently with positive family history, whose main clinical features are early social and personal behavioral disturbances, cognitive defects mainly in attention, language and executive functions, personality disorders and blunt, unconcerned and subdepressive affect. Anatomic and functional neuroimaging shows atrophy and functional defects in anterior brain regions, and the EEG is persistently normal. Although frontotemporal dementia has been confounded with Alzheimer's disease for long time, it can be identified on clinical grounds in order to perform new therapeutic trials.

To develop and assess the consistency and validity of simple cognitive function measures for an elderly population with low levels of formal education for use in a longitudinal study of dementia.Data were from the population longitudinal study 'Growing old in Leganés' (Spain). In 1993, a random sample of 1540 people over 65 was drawn from the City Roll of Leganés from which 1284 (83%) were successfully interviewed. Measures of memory and orientation were based on the SPMSQ (Short Portable Mental Status Questionnaire), the Barcelona test and the short story from EPESE (Established Populations Epidemiologic Studies of the Elderly). Non-response to a test item was coded as an error. Internal consistency was assessed by factor analysis and Cronbach's alpha. Construct validity was examined with multiple linear regressions of the proposed measurements on variables chosen from the existing literature on cognitive function.Two factors, memory and orientation, emerged from the factor analysis. Internal consistency of the proposed indexes for memory and orientation was acceptable. Memory and orientation scores were summed into one summary index of cognition. Associations between covariates and both cognitive indexes were in the expected direction. Among those highly functional, orientation was influenced by illiteracy due to higher error rates in the time orientation items based on dates; however, memory and summary scores were not significantly different by literacy status. A large proportion of the variance in IADL was explained by the memory and orientation measures.The memory and orientation indexes are valid and reliable measurements of cognitive function for use in a population of community dwelling elderly with low levels of formal education and high rates of illiteracy.

There are several Spanish versions and adaptations of the Mini-Mental State Examination (MMSE), the most used abbreviated test for screening of the cognitive decline in clinical and epidemiological setting. Among them, the Mini-Examen Cognoscitivo (MEC) is highlighted. The aim of this study was to compare the diagnostic usefulness between the Spanish translation of the MMSE (the MMSE1 which incorporates the proof of serial "sevens" and the MMSE2 which includes spelling "world" backward) and the MEC for the diagnosis of dementia.A sample of elderly persons (65 years or over), included in a population-based study of dementia prevalence. The diagnosis of dementia was assessed through exhaustive neuropsychological evaluation. The diagnosis of dementia (according to the standardized DSM-III-R criteria) was carried out by expert neurologists, who were independent and blind to the scores obtained in the MMSE and MEC.79 subjects underwent both tools and neuropsychological assessment. The MMSE1 obtained the highest accuracy (92%), followed by the MEC (90%) and the MMSE2 (83%). The analysis of the areas under receiver operating characteristic curves did not show significant statistical differences between the MMSE1 and MEC (p = 0.38), but significant differences were observed between those and the MMSE2 (p = 0.01).The diagnostic usefulness of Spanish translation of the MMSE is similar to the MEC. The proof of spelling "world" backward obtained poorer results than serial "sevens". The Spanish versions of the MMSE should be improved to be adapted to our cultural characteristics.

White matter changes (WMC), detected by imaging techniques, are frequent in stroke patients. The aim of the study was to determine how WMC relate to stroke subtypes and to stroke outcome. We made a systematic Medline search for articles appearing with two of the following key words: either 'WMC or white matter lesions or leukoencephalopathy or leukoaraiosis' and 'stroke or cerebral infarct or cerebral hemorrhage or cerebrovascular disease or transient ischemic attack (TIA)'. WMC, as defined radiologically, are present in up to 44% of patients with stroke or TIA and in 50% of patients with vascular dementia. WMC are more frequent in patients with lacunar infarcts, deep intracerebral hemorrhages, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and cerebral amyloid angiopathy. After an acute ischemic stroke, WMC are associated with a higher risk of death or dependency, recurrent stroke of any type, cerebral bleeding under anticoagulation, myocardial infarction, and poststroke dementia. WMC in stroke patients are often associated with small-vessel disease and lead to a higher risk of death, and poor cardiac and neurological outcome. However, several questions remain open and need further investigations.

To study main factors determining medical decision in admitting patients with acute cerebrovascular disease (ACVD).This is an observational and transversal study. We analyze a hospitalary cohort made by all consecutive patients with ACVD coming to Emergency Room to Hospital Universitario de la Princesa during 1 year. Neurologist on call made on his/her own decision to admit the patient to hospital. Clinical and epidemiological characteristics of those patients admitted with those who went home are compared.517 patients were studied, 147 had transient ischemic attacks (TIA) and 370 had a stroke, 12.3% TIA and 68.4% stroke patients were hospitalized. Age, Canadian Stroke Scale (CSS) on admission, subtype of stroke, atrial fibrillation and abnormal EKG, old lesions in CT, previous TIA and/or CVD, diminished conscious level, orientation and language, sphincter control and evolution time greater than 48 hours were statistically significative in deciding admission. Logistic regression analysis (84.2% total predictive value) showed independent predictive value in age, CSS, previous CVD and some subtypes of stroke (ischemic non lacunar and hemorrhage).We hospitalize younger patients, with a worse clinical condition and overall hemorrhagic stroke. The percentage of admissions among TIA patients is low. On the other hand, date, time and physicians-team features do not affect the percentage of admissions.

Since the recognition of white matter changes on CT (leukoaraiosis), rating scales for the location and severity of white matter changes have been developed, mainly for research purposes, to investigate factors such as the relation with cognition, risk factors, and pathology. The main purpose of rating scales is to provide scores that can be used in statistical analyses. The development of the NINDS-AIREN criteria for vascular dementia have introduced a new application for these rating scales in investigating and delineating the amount of white matter changes on CT/MRI sufficient to fulfill the criteria. Furthermore, in Alzheimer's disease, recognition of white matter changes may serve to delineate homogeneous groups and help to identify patients with different symptomatology. We reviewed the existing rating scales for CT and MRI and judged their properties and reliability. The ideal rating scale does not yet exist, but different rating scales may serve different purposes, for which some recommendations are made.

The aim of this pilot study was to analyze an adaptation of the PDQ-39, a Parkinson's disease (PD) quality of life questionnaire, for use in Spanish. Fifty patients were enrolled. Patient characteristics and medical histories were recorded, including scores on the following scales: Hoehn and Yahr (HY), PD unified (UPDRS), Schwab and England (SE), Intermediate Scale for Assessment of PD (ISAPD). Barthel Index (BI), Pfeiffer's SPMSQ, Global Deterioration Scale (GDS), Geriatric Depression Scale (GDS). Hospital Depression and Anxiety Scale (HDA) and the PDQ-39. Descríptive statistics were recorded, as well as Spearman's r and ANOVA results. The dimensions that correlated well with PD scale scores were mobility, daily life activities and cognitive deterioration. The dimension stigma correlated with complications on the UPDRS and the ISAPD. Emotional well-being correlated with subscale I of the UPDRS, the GDS and the HDA (r = 0.39-0.79, p0.01-0.001). Physical discomfort correlated only with depression and anxiety. Stage of disease and level of depression influenced most dimensions assessed by the PDQ-39. Some psychosocial factors that are important components of well-being are scarcely reflected by the clinical scales usually applied.

The present study is devoted to the verification of the basic metrical characteristics of the ISAPD. One hundred and sixty-seven Parkinson's disease (PD) patients were included. Group A (n = 40) was simultaneously assessed by five raters who applied the ISAPD and other PD rating scales (PDRS). A set of timed tests, the MiniMental State Examination (MMSE) and the Hamilton Scale for Depression (HSD) were administered by an independent examiner. Group B (n = 127) was individually assessed through the UPDRS and the other PDRSs by separate neurologists in four different hospitals. The ISAPD was administered in 7.0 +/- 3.7 min. The internal consistency of this scale was high (Cronbach's alpha = 0.97). The inter-rater reliability of their items was very satisfactory (for all items, kappa > 0.70). There was a high correlation with the Hoehn and Yahr classification (r(s) = 0.71; p < 0.001) and some timed tests. The convergent validity with the other PDRS (UPDRS and Schwab and England Scale) was also very high (r(s) = 0.83-0.92; p < 0.001). The ISAPD also correlated with the MMSE and the HSD. Factor analysis identified three factors (activities of daily living; gait and mobility; speech and eating) that explained 76% of the variance. The ISAPD is an easy to apply, reliable, and valid scale that fulfills the aim for which it was designed.

We report the objectives and case registration methods used by neurologists belonging to the Spanish Neurological Society's dementia group (GERMICIDE). Forerunners of the present project are also described. The group's principal aim, which is to determine the distribution of dementia in the "neurological" environment is pursued by enrolling consecutive index cases (new presentations) arriving at 18 Spanish neurological units over a period of 2 years. A standard protocol was used to study the patients and final diagnoses were agreed upon in keeping with international criteria for dementia and the main neurological diseases (DSM-III-R, CDR and others). A second objective is to study risk factors for the main etiological groups of dementia (Alzheimer's disease and vascular dementia) and to follow each patient in the cohort until death in order to assess the course of disease and its biological markers. The series will be large, as there are already over 800 cases listed in the coordinating centre even though the period of enrollment has not ended.

Chronic alcoholic patients frequently exhibit a mild to moderate cognitive impairment that has been related to Wernicke-Korsakoff encephalopathy and attributed tentatively to nutritional and vitamin deficiencies. To elucidate the possible relation between alcoholic cognitive deterioration (ACD) and nutritional and vitamin deficiencies, several tests of intelligence and memory were administered to 54 chronic alcoholic patients and 30 controls. Serum levels of thiamine, folic acid, vitamins B12, A, and E, and certain nutritional indexes were determined in most of the subjects. The alcoholics scored significantly lower in intellectual and visuospatial tasks but not in verbal memory tasks. They had a lower serum level for thiamine but not of the remaining vitamins. However, the correlations between serum thiamin and cognitive performance scores were low, and according to stepwise regression analysis, duration of alcohol intake and education were the variables with predictive value for intellectual and memory test performance. These results suggest that serum thiamin deficiency is not the main pathogenetic factor related to ACD.