Microhemorragias cerebrales: epidemiología e implicaciones clínicas / Brain microbleeds: Epidemiology and clinical implications

INTRODUCCIÓN: Las microhemorragias cerebrales (MHC) son depósitos de hemosiderina, fagocitados por macrófagos, que se visualizan como imágenes hipointensas en determinadas secuencias de adquisición T2 de resonancia magnética cerebral. Existen muchas incógnitas acerca de su fisiopatología y significado clínico. DESARROLLO: Revisión bibliográfica de los principales estudios epidemiológicos, clínicos y anatomopatológicos de MHC en la población general, en pacientes con enfermedad o riesgo vascular y en pacientes con deterioro cognitivo. Descripción de la prevalencia, factores de riesgo, mecanismos fisiopatológicos y posibles implicaciones clínicas de las MHC. CONCLUSIONES: La prevalencia de las MHC es muy variable (3-27% en la población general, 6-80% en pacientes con enfermedad o riesgo vascular, 16-45% en pacientes con deterioro cognitivo). Las MHC se asocian a la edad, a la enfermedad de Alzheimer y, en particular, a la enfermedad vascular (hemorrágica o isquémica) cerebral. El sustrato patológico es la lipohialinosis (MHC subcorticales) o la angiopatía amiloide cerebral (MHC lobulares). Las MHC contribuyen al deterioro cognitivo, posiblemente a través de una desconexión córtico-subcortical e intracortical, y se asocian a una mayor mortalidad, especialmente de causa vascular. Las MHC aumentan el riesgo de sufrir hemorragia cerebral, especialmente en pacientes con múltiples MHC lobulares (probable angiopatía amiloide cerebral), por lo que el tratamiento anticoagulante podría estar contraindicado en estos pacientes. En pacientes con menor riesgo de sangrado, los nuevos anticoagulantes orales y la realización de un seguimiento combinado -clínico y mediante resonancia magnética- podrían ser útiles en la toma de decisiones

INTRODUCTION: Brain microbleeds (BMB) are haemosiderin deposits contained within macrophages, which are displayed as hypointense images in some T2-weighted magnetic resonance imaging sequences. There are still many questions to be answered about the pathophysiology and clinical relevance of BMB. DEVELOPMENT: We conducted a literature review of the main epidemiological, clinical, and anatomical pathology studies of BMB performed in the general population, in patients at risk of or already suffering from a vascular disease, and in patients with cognitive impairment. We analysed the prevalence of BMB, risk factors, and potential pathophysiological mechanisms and clinical implications. CONCLUSIONS: The prevalence of BMB is highly variable (3%-27% in the general population, 6%-80% in patients with vascular risk factors or vascular disease, and 16%-45% in patients with cognitive impairment). BMB are associated with ageing, Alzheimer disease (AD), and in particular haemorrhagic or ischaemic cerebrovascular disease. The pathological substrate of BMB is either lipohyalinosis (subcortical BMB) or cerebral amyloid angiopathy (lobar BMB). BMB exacerbate cognitive impairment, possibly through cortical-subcortical and intracortical disconnection, and increase the risk of death, mostly due to vascular causes. BMB also increase the risk of cerebral haemorrhage, particularly in patients with multiple lobar BMB (probable erebral amyloid angiopathy). Therefore, anticoagulant treatment may be contraindicated in these patients. In patients with lower risk of bleeding, the new oral anticoagulants and the combination of clinical and magnetic resonance imaging follow-up could be helpful in the decision-making process

Brain microbleeds: Epidemiology and clinical implications. / Microhemorragias cerebrales: epidemiología e implicaciones clínicas.

INTRODUCTION: Brain microbleeds (BMB) are haemosiderin deposits contained within macrophages, which are displayed as hypointense images in some T2-weighted magnetic resonance imaging sequences. There are still many questions to be answered about the pathophysiology and clinical relevance of BMB. DEVELOPMENT: We conducted a literature review of the main epidemiological, clinical, and anatomical pathology studies of BMB performed in the general population, in patients at risk of or already suffering from a vascular disease, and in patients with cognitive impairment. We analysed the prevalence of BMB, risk factors, and potential pathophysiological mechanisms and clinical implications. CONCLUSIONS: The prevalence of BMB is highly variable (3%-27% in the general population, 6%-80% in patients with vascular risk factors or vascular disease, and 16%-45% in patients with cognitive impairment). BMB are associated with ageing, Alzheimer disease (AD), and in particular haemorrhagic or ischaemic cerebrovascular disease. The pathological substrate of BMB is either lipohyalinosis (subcortical BMB) or cerebral amyloid angiopathy (lobar BMB). BMB exacerbate cognitive impairment, possibly through cortical-subcortical and intracortical disconnection, and increase the risk of death, mostly due to vascular causes. BMB also increase the risk of cerebral haemorrhage, particularly in patients with multiple lobar BMB (probable erebral amyloid angiopathy). Therefore, anticoagulant treatment may be contraindicated in these patients. In patients with lower risk of bleeding, the new oral anticoagulants and the combination of clinical and magnetic resonance imaging follow-up could be helpful in the decision-making process.

Aplicación práctica de los test cognitivos breves / Practical application of brief cognitive tests

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

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

Practical application of brief cognitive tests.

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.

Brain Donation by Proxy: Are There Predictors in Neurodegenerative Dementia?

OBJECTIVES: To describe the frequency and predictors of brain donation by relatives in patients with neurodegenerative dementia. DESIGN: Database review and quantitative analysis. SETTING: The Alzheimer Center Reina Sofia Foundation (ACRSF), a center devoted to the care and research of patients with neurodegenerative dementia. PARTICIPANTS: Patients with signed consent for participation in the ACRSF research program. MEASUREMENTS: A set of 38 demographic, clinical, and social variables related to patient and closest relative, which were collected by the ACRSF multidisciplinary team upon patient admission. RESULTS: Admission data were available for 198 patients who entered the ACRSF research program; 85 of them (42.9%) died during follow-up. Mean age (SD) at admission was 82.3 (6.8) years and 80.8% of the patients were female. Family link between patient and closest relative was spouse or partner (12.0%), son or daughter (74.9%), or other link (13.1%). Brain was obtained from 56 patients (65.9%). Consent by legal representative and patient's depressive symptoms were more frequent in the donors (p<0.05, corrected) and trend was observed for more aberrant motor symptoms in the donors (p<0.05, uncorrected). CONCLUSION: A high rate of brain donation was achieved, probably due to the unique characteristics of the ACRSF and consent for research policy. Wish of alleviating suffering, as well as general interest in dementia research, possibly exerted an influence in brain donation. More research is needed to ascertain the values, motivations, and circumstances that may lead to brain donation by proxy in neurodegenerative dementia.

Cumulative effect of depression on dementia risk.

Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer's disease (AD), with control of vascular factors (VFs). Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES) study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (nD), past depression (pD), present depression (prD), and present and past depression (prpD). Logistic regression was used. Results. Data of 1,807 subjects were investigated at baseline (mean age 74.3, 59.3% women), and 1,376 (81.6%) subjects were evaluated after three years. The prevalence of dementia at baseline was 6.7%, and dementia incidence was 6.3%. An effect of depression was observed on dementia prevalence (OR [CI 95%] 1.84 [1.01-3.35] for prD and 2.73 [1.08-6.87] for prpD), and on dementia due to AD (OR 1.98 [0.98-3.99] for prD and OR 3.98 [1.48-10.71] for prpD) (fully adjusted models, nD as reference). Depression did not influence dementia incidence. Conclusions. Present depression and, particularly, present and past depression are associated with dementia at old age. Multiple mechanisms, including toxic effect of depression on hippocampal neurons, plausibly explain these associations.

Psychometric properties of the Spanish QoL-AD with institutionalized dementia patients and their family caregivers in Spain.

OBJECTIVES: To evaluate the psychometric attributes of the Spanish version of the Quality of Life-Alzheimer's Disease Scale (QoL-AD) in institutionalized patients and family caregivers in Spain. METHOD: 101 patients (88.1% women; mean age, 83.2 ± 6.3) with Alzheimer's disease (AD) (n = 82) and mixed dementia (n = 19) and their closest family caregivers. Patient-related variables included severity of dementia, cognitive status, perceived general health, quality of life, behavior, apathy, depression, and functional status. QoL-AD acceptability, reliability, and construct validity were analyzed. RESULTS: The mean Mini-Mental State Examination (MMSE) score was 7.2 ± 6.1 and Global Deterioration Scale was: stage four (4%); five (21.2%); six (34.3%); and seven (40.4%). Both, QoL-AD patient version (QoL-ADp) (n = 40; MMSE = 12.0 ± 4.5) and QoL-AD caregiver version (QoL-ADc) (n = 101) lacked significant floor and ceiling effects and the Cronbach α index was 0.90 and 0.86, respectively. The corrected item-total correlation was 0.11-0.68 (QoL-ADc) and 0.28-0.84 (QoL-ADp). Stability was satisfactory for QoL-ADp (intraclass correlation coefficient [ICC]=0.83) but low for QoL-ADc (ICC = 0.51); the standard error of measurement was 2.72 and 4.69. Construct validity was moderate/high for QoL-ADc (QUALID=-0.43; EQ-5D = 0.65), but lower for QoL-ADp. No significant correlations were observed between QoL-ADp and patient variables or QoL-ADc. A low to high association (r = 0.18-0.55) was obtained between QoL-ADc and patient-related measures of neuropsychiatric, function, and cognitive status. CONCLUSION: Differences in their psychometric attributes, and discrepancy between them, were found for QoL-ADp and QoL-ADc. In patients with AD and advanced dementia, the QoL perceived by the patient could be based on a construct that is different from the traditional QoL construct.

Cortical excitability in very mild Alzheimer's disease: a long-term follow-up study.

Measurement of motor cortex excitability using paired-pulse transcranial magnetic stimulation (pTMS) has been proposed for the early diagnosis of Alzheimer's disease (AD) and could also be useful for monitoring treatment response and disease progression. However, studies conducted at the pre-dementia stage of AD are scarce, very few long-term data are available, and correlations between cortical excitability and cognitive performance have not been addressed. Eleven patients with mild cognitive impairment (MCI) that converted to AD-related dementia and 12 elderly control subjects were selected for this study. Cognitive assessments and pTMS were conducted at baseline in the two groups and also after 4 and 21 months of treatment with donepezil in the AD group. Non-parametric statistics were used to compare cortical excitability between the two study groups at baseline and to analyse disease course in the AD group. Correlation analysis was performed to investigate associations between cortical excitability and cognitive performance. Short-latency intracortical inhibition (SICI) and intracortical facilitation were reduced in AD patients. However, there was high inter-individual variability, and statistical significance was only attained at a 2-ms interstimulus interval (ISI). A trend towards recovery of 2-ms SICI was observed after treatment with donepezil. Baseline cortical excitability at 300 ms was associated with better cognitive performance in AD patients. Although the present results do not support a role for pTMS in the early diagnosis of late-onset AD, a potential role in prediction of treatment response and understanding of disease mechanisms emerged.

[Quality of neurological care in the emergency services: a study from the community-hospital]. / Calidad de la asistencia neurológica en urgencias: un estudio desde el área.

INTRODUCTION: The medical conditions shared by hospital emergency services and community-hospital neurology clinics (CHNC) have not been described, and the quality of the medical care received in these conditions has not been evaluated in our environment. METHODS: Over a 2 month period, those patients presenting at any of the seven CHNC in a Health Care Area 1 of Madrid due to previously attended medical conditions in the emergency services were systematically registered. The area neurologists of the CHNC collected administrative and clinical variables and made a judgment on the medical care (primary outcome measure) and diagnoses (secondary outcome measure) received. RESULTS: A total of 181 patients were included (mean age: 58 years; 60% women). The inclusion rate was one patient per working day, and 31% of patients were visited out of the established quota number of patients for the clinic. The most frequent reasons for visiting the emergency room were: headache (20%), focal neurological syndrome (16%) and loss of consciousness (14%). The most frequent diagnoses at the CHNC were: primary headache (19 %), stroke (11%) and epilepsy (9 %). Emergency care was deemed correct in 56 % of patients. When the patients with intervention were compared to those with no intervention, participation of the neurology service in the emergency room was associated to a greater percentage of correct diagnoses (59% vs. 41%; p=0.019) and care (69% vs. 47%; p=0.003). CONCLUSIONS: The medical conditions shared with the emergency services represent a small but relevant proportion of the patients assisted in the CHNC. Some of these conditions (primary headaches, syncopes) should be canalized into primary health care. Others (epilepsy) require a circuit between emergency room and CNNC, but the appointment system should be adapted. The intervention of a neurologist in the emergency room raises the quality of the care.

Consistency of clinical diagnosis of dementia in NEDICES: A population-based longitudinal study in Spain.

BACKGROUND: Few longitudinal studies have verified the clinical diagnosis of dementia based on clinical examinations. We evaluated the consistency of the clinical diagnosis of dementia over a period of 3 years of follow-up in a population-based, cohort study of older people in central Spain. METHODS: Individuals (N = 5278) were evaluated at baseline (1994-1995) and at follow-up (1997-1998). The evaluation included a screening questionnaire for dementia and a neurological assessment. RESULTS: Dementia screening consisted of a 37-item version of the Mini-Mental State Examination (MMSE) and the Pfeffer Functional Activities Questionnaire (FAQ). Study neurologists investigated those participants who screened positively (N = 713) as well as 843 who had screened negatively to test the sensitivity of the screening instruments or because they had a positive screening for other chronic neurological diseases. We detected 295 patients among those who screened positive and 13 among those who screened negatively. Three years follow-up evaluation demonstrated 14 diagnostic errors at baseline (4.5%) leading to a final number of 306 patients with dementia. The corrected prevalence of dementia was 5.8% (95% confidence interval [CI] 5.2-6.5). CONCLUSIONS: The diagnosis of dementia was highly accurate in this population-based, Spanish cohort study, and our prevalence figures agree with other European surveys. Given the high cost and difficulties of population rescreening and its relatively low yield, we conclude that a single 2-phase investigation (screening followed by clinical examination) provides accurate information for most population-based prevalence studies of dementia.

Cognitive dysfunction in systemic lupus erythematosus: prevalence and correlates.

Little is known about the mechanisms and relevance of cognitive dysfunction in systemic lupus erythematosus (SLE) patients who never displayed major neuropsychiatric manifestations (nSLE). Thirty-one nSLE female patients and 31 cognitively healthy control women were recruited. Sociodemographic, clinical, neuropsychological and SLE-related markers were collected including cerebral perfusion by single-photon emission computed tomography. Prevalences of cognitive complaints were 22.6% in nSLE versus 6.5% in the control group (p = 0.147); respective prevalences of cognitive dysfunction were 32.3 versus 6.5% (p = 0.01). Within the nSLE group, all cognitive domains appeared similarly affected, and correlations were found between cognitive dysfunction and less skilled occupation (r = -0.41, p = 0.02) and between cognitive complaints and depressive symptoms (r = 0.35, p = 0.05). Cognitive dysfunction is rather frequent in nSLE and seems to negatively impinge on social functioning.

Cognitive dysfunction in multiple sclerosis: methods and prevalence from the GEDMA Study.

BACKGROUND/AIMS: Cognitive dysfunction is a major handicap in multiple sclerosis (MS). Its prevalence varies due to disease heterogeneity and methodological issues. A neuropsychological battery of intermediate size was designed for and explored in the screening of cognitive dysfunction in MS patients. METHODS: The battery was administered to a hospital-based sample of 191 MS patients and 50 matched controls. Eleven test scores measuring verbal fluency, verbal learning, attention, calculation and visuoperceptual ability were selected on the basis of sensitivity and lack of redundancy. Two alternative approaches were compared for diagnosis of cognitive dysfunction based, firstly, on the number of failed tasks, and secondly, on a single standardized global score. RESULTS: The approach based on the number of failed tasks discriminated better than did the global approach between patients and controls. Using a cutoff of two altered scores, a cognitive dysfunction prevalence of 34% was obtained. The score yielded after summing errors in all tests was the most frequently altered and proved particularly useful for detecting minimally impaired patients. CONCLUSION: The purpose-designed battery was adequate for the screening of cognitive dysfunction in MS patients. The better accuracy of the single-task approach might reflect MS heterogeneity.

Calidad de la asistencia neurológica en urgencias: un estudio desde el área / Quality of neurological care in the emergency services: a study from the community-hospital

Introducción. Los procesos compartidos por los servicios hospitalarios de urgencias y las consultas de neurología del área sanitaria (CNA) no han sido descritos y su calidad asistencial no ha sido evaluada en nuestro medio. Métodos. Durante 2 meses se registraron todos los pacientes que acudieron a las siete CNA 1 de Madrid debido a procesos médicos que habían sido previamente atendidos en urgencias. Los neurólogos del área sanitaria recogieron variables organizativas y clínicas y emitieron un juicio acerca de la asistencia (variable de efecto primaria) y del diagnóstico (variable de efecto secundaria) realizados. Resultados. Fueron incluidos 181 pacientes (edad media: 58 años; 60% mujeres), a un promedio de un paciente por día de consulta. El 31% estaban citados fuera del cupo. Los motivos más frecuentes de la visita a urgencias habían sido: cefalea (20%), focalidad neurológica (16 %) y pérdida de conciencia (14 %). Los diagnósticos más frecuentes en la CNA fueron: cefalea primaria (19%), accidente cerebrovascular (11%) y epilepsia (9 %). La asistencia en urgencias fue correcta en el 56% de los pacientes. Comparado con los procesos en que no intervino, la participación de neurología se asoció a un mayor porcentaje de diagnóstico y de asistencia correctos (59 frente a 41%; p=0,019, y 69 frente a 47%; p=0,003, respectivamente). Conclusiones. Los procesos compartidos con urgencias suponen una proporción pequeña pero no desdeñable del total de pacientes atendidos en las CNA. Algunos de estos procesos (cefaleas primarias, síncopes) deberían canalizarse hacia la asistencia primaria. Otros (epilepsia) precisan del circuito urgencias-CNA, pero el sistema de citaciones debe adaptarse. La actuación del neurólogo en urgencias eleva la calidad asistencial (AU)

Introduction: The medical conditions shared by hospital emergency services and community-hospital neurology clinics (CHNC) have not been described, and the quality of the medical care received in these conditions has not been evaluated in our environment. Methods: Over a 2 month period, those patients presenting at any of the seven CHNC in a Health Care Area 1 of Madrid due to previously attended medical conditions in the emergency services were systematically registered. The area neurologists of the CHNC collected administrative and clinical variables and made a judgment on the medical care (primary outcome measure) and diagnoses (secondary outcome measure) received. Results: A total of 181 patients were included (mean age: 58 years; 60% women). The inclusion rate was one patient per working day, and 31% of patients were visited out of the established quota number of patients for the clinic. The most frequent reasons for visiting the emergency room were: headache (20%), focal neurological syndrome (16%) and loss of consciousness (14%). The most frequent diagnoses at the CHNC were: primary headache (19 %), stroke (11%) and epilepsy (9 %). Emergency care was deemed correct in 56 % of patients. When the patients with intervention were compared to those with no intervention, participation of the neurology service in the emergency room was associated to a greater percentage of correct diagnoses (59% vs. 41%; p=0.019) and care (69% vs. 47%; p=0.003). Conclusions: The medical conditions shared with the emergency services represent a small but relevant proportion of the patients assisted in the CHNC. Some of these conditions (primary headaches, syncopes) should be canalized into primary health care. Others (epilepsy) require a circuit between emergency room and CNNC, but the appointment system should be adapted. The intervention of a neurologist in the emergency room raises the quality of the care (AU)

[Clinical validity of two scales of instrumental activities in Alzheimer's disease]. / Validez clínica de dos escalas de actividades instrumentales en la enfermedad de Alzheimer.

INTRODUCTION: Activities of daily living (ADL) are a major domain in the clinical assessment of Alzheimer's disease (AD) patients. However, ADL scales have not been sufficiently validated in Spain. METHODS: Patients attending a neurology outpatient clinic were classified according to the global deterioration scale (GDS). Afterwards, an independent evaluator administers two scales of instrumental activities of daily living (IADL): Lawton and Brody's scale of IADL (SIADL) and Pfeffer's functional activities questionnaire (FAQ). The SIADL was scored in the original way (dichotomic) (SIADLd) and in an alternative way (ordinal) (SIADLo). Internal consistency (Cronbach alpha coefficient), test-retest reliability (intraclass correlation coefficient), diagnostic validity (sensitivity, specificity, number of patients correctly classified) and influence of different variables (regression analysis) were analyzed for the SIADLd, the SIADLo and the FAQ. RESULTS: Ninety-eight patients were recruited. Internal consistency, reliability and diagnostic validity were good or excellent for the three scales. The SIADLo showed better diagnostic and scale features than the SIADLd, but the FAQ surpassed both in all the studied variables. No scale was able to make a proper distinction between patients with subjective complaints (GDS 2) and patients without complaints (GDS 1). Sex and age influenced the SIADL score, but not the FAQ score. The FAQ reached a sensitivity of 0.95 and a specificity of 0.88 in the screening of dementia. CONCLUSIONS: The SIADL and the FAQ are useful, valid and reliable tools for the clinical assessment of AD patients. Ordinal scoring is more advantageous than dichotomic scoring in the SIADL, but the FAQ is preferable.

Validez clínica de dos escalas de actividades instrumentales en la enfermedad de Alzheimer / Clinical validity of two scales of instrumental activities in Alzheimer's disease

Introducción. Las actividades de la vida diaria (AVD) constituyen uno de los ejes principales en la valoración clínica de los pacientes con enfermedad de Alzheimer (EA). Apenas se han llevado a cabo estudios de validación de escalas de AVD en España. Métodos. Los pacientes de una consulta neurológica general fueron clasificados según la escala de deterioro global (GDS). Posteriormente, una evaluadora independiente administró dos escalas de actividades instrumentales de la vida diaria (AIVD): la escala de AIVD de Lawton y Brody (EAIVD) y el cuestionario de actividades funcionales de Pfeffer (CAF). La EAIVD fue puntuada según el modo original (dicotómico) (EAIVDd) y de una forma alternativa (ordinal) (EAIVDo). Se estudió la consistencia interna (coeficiente ex de Cronbach). la fiabilidad test-retest (coeficiente de correlación intraclase), el rendimiento diagnóstico (sensibilidad, especificidad, pacientes correctamente clasificados) y la influencia de distintas variables (análisis de regresión) en la EAIVDd, la EAIVDo y el CAF. Resultados. Se reclutaron 98 pacientes. La consistencia interna, la fiabilidad y el rendimiento diagnóstico de las tres escalas fueron buenos o excelentes. La EAIVDo presentó mejores propiedades diagnósticas y escalares que la EAIVDd, pero el CAF superó a ambas en todos los índices analizados. Ninguna escala consiguió discriminar adecuadamente a los pacientes con quejas subjetivas (GDS 2) respecto de los pacientes sin quejas (GDS 1). El sexo y la edad influyeron en la EAIVD, pero no en el CAF, que alcanzó una sensibilidad de 0,95 y una especificidad de 0,88 en el cribado de la demencia. Conclusiones. La EAIVD y el CAF son herramientas útiles, válidas y fiables en la valoración clínica de la EA. La puntuación ordinal es más ventajosa que la puntuación dicotómica en la EAIVD. Con todo, el CAF es preferible

Introduction. Activities of daily living (ADL) are a major domain in the clinical assessment of Alzheimer's disease (AD) patients. However, ADL scales have not been sufficiently validated in Spain. Methods. Patients attending a neurology outpatient elinic were elassified according to the global deterioration scale (GDS). Afterwards, an independent evaluator administeres two scales of instrumental activities of daily living (IADL): Lawton and Brody's scale of IADL (SIADL) and Pfeffer's functional activities questionnaire (F AQ). The SIADL was scored in the original way (dichotomic) (SIADLd) and in an alternative way (ordinal) (SIADLo). Internal consistency (Cronbach ex coefficient), test-retest reliability (intraclass correlation coefficient), diagnostic validity (sensitivity, specificity, number of patients correctly elassified) and influence of different variables (regression analysis) were analyzed for the SlADLd, the SIADLo and the FAQ. Results. Ninety-eight patients were recruited. Internal consistency, reliability and diagnostic validity were good or exce11ent for the three scales. The SIADLo showed better diagnostic and scale features than the SIADLd, but the FAQ surpassed both in a11 the studied variables. No scale was able to make a proper distinction between patients with subjective complaints (GDS 2) and patients without complaints (GDS 1). Sex and age influenced the SlADL score, but not the FAQ score. The FAQ reached a sensitivity of 0.95 and a specificity of 0.88 in the screening of dementia. Conclusions. The SIADL and the FAQ are useful, valid and reliable tools for the elinical assessment of AD patients. Ordinal scoring is more advantageous than dichotomic scoring in the SIADL, but the FAQ is preferable

[Regional correlations between MR imaging perfusion and SPECT in Alzheimer's disease]. / Correlaciones regionales entre el estudio de la perfusión mediante resonancia magnética y SPECT en la enfermedad de Alzheimer.

INTRODUCTION: Dynamic susceptibility contrast (DSC) is a magnetic resonance (MR) technique that provides an estimation of cerebral blood flow (CBF) through the obtention of a cerebral blood volume map. As observed with nuclear medicine methods, DSC MR studies have demonstrated a temporoparietal hypoperfusion in Alzheimer's disease (AD). However, the concurrent validity of DSC and nuclear medicine techniques has not been sufficiently investigated. PATIENTS AND METHODS: A single-photon emission computed tomography (SPECT) and a DSC MR perfusion study were performed consecutively in 14 AD patients. Expert based qualitative assessments of CBF were carried out in eight regions of interest (ROI). RESULTS: Level of agreement in the studied ROI was highly variable. Presence of large blood vessels and patient head movement were possibly the main causes of this variability. Nevertheless, when interrater variability was eliminated, intraclass correlation coefficients became more uniform, ranging from 0.32 to 0.71. CONCLUSIONS: DSC MR imaging was concordant with SPECT at the different cerebral lobes of AD patients. The positive findings should be confirmed under better technical and methodological conditions.

Regional correlations between MR imaging perfusion and SPECT in Alzheimer's disease

Introducción. El contraste por su susceptibilidad dinámica (CSD) es una técnica de resonancia magnética (RM) que ofrece una estimación del flujo sanguíneo cerebral (FSC) a través de la obtención de un mapa de volumen sanguíneo cerebral. Al igual que ocurre con las técnicas de medicina nuclear, los estudios mediante CSD han mostrado una hipoperfusión temporoparietal en pacientes con enfermedad de Alzheimer (EA). Sin embargo, la validez concurrente del CSD respecto a las técnicas de medicina nuclear no ha sido suficientemente investigada. Pacientes y métodos. Se realizaron de forma consecutiva un estudio de tomografía por emisión de fotón único (SPECT) y un estudio de perfusión mediante CSD a 14 pacientes con EA. Se llevó a cabo una valoración cualitativa por parte de expertos en ocho regiones de interés (ROI). Resultados. El nivel de concordancia entre las dos técnicas en las distintas ROI fue muy variable. La presencia de grandes vasos y el movimiento de la cabeza durante el tiempo de adquisición fueron posiblemente las principales causas de esta variabilidad. Con todo, una vez eliminada la variabilidad interobservador, los coeficientes de correlación intraclase fueron más uniformes, situándose entre 0,32 y 0,71. Conclusiones. El CSD y el SPECT fueron concordantes en los distintos lóbulos cerebrales de pacientes con EA. Estos resultados positivos han de ser confirmados bajo mejores condiciones técnicas y metodológicas

Introduction. Oynamic susceptibility contrast (DSC) is a magnetic resonance (MR) technique that provides an estimation of cerebral blood flow (CBF) through the obtention of a cerebral blood volume map. As observed with nuclear medicine methods, DSC MR studies have demonstrated a temporoparietal hypoperfusion in Alzheimer's disease (AD). However, the concurrent validity of DSC and nuclear medicine techniques has not been sufficiently investigated. Patients and methods. A single-photon emission computed tomography (SPECT) and a DSC MR perfusion study were performed consecutively in 14 AD patients. Expert based qualitative assessments of CBF were carried out in eight regions of interest (ROI). Results. Level of agreement in the studied ROI was highly variable. Presence of large blood vessels and patient head movement were possibly the main causes of this variability. Nevertheless, when interrater variability was eliminated, intraclass correlation coefficients became more uniform, ranging from 0.32 to 0.71. Conclusions. DSC MR imaging was concordant with SPECT at the different cerebral lobes of AD patients. The positive findings should be confirmed under better technical and methodological conditions

Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease.

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.

Selective memory impairment on an adapted Mini-Mental State Examination increases risk of future dementia.

OBJECTIVE: To determine whether selective memory impairment (SMI) on an adapted Mini-Mental State Examination (aMMSE) test increases risk of future dementia in a population-based survey of central Spain. BACKGROUND: SMI is a strong predictor of dementia in the elderly. However, most approaches have used extensive memory batteries, which are not always suitable for screening purposes. METHODS: The basal cohort consisted of 2982 poorly educated individuals aged 65 or over. Dementia, stroke and parkinsonism cases were previously excluded. At entry, participants received a structured interview including an aMMSE. Two groups were created according to basal cognitive performance, namely: (1) aMMSE > 23 and no word remembered on the aMMSE delayed-recall task (SMI group); and (2) aMMSE > 23 and at least one word remembered on the delayed-recall task (control group). In a three-year follow-up wave, conversion rate to dementia was calculated and logistic regression was performed. RESULTS: Of a total of 2507 subjects who completed the two evaluations, 280 qualified for SMI at entry. In the SMI group, 25 subjects (8.9%) developed dementia vs 26 subjects (1.2%) in the control group. Taking the two groups together, and once demographic and medical variables had been controlled, a low delayed-recall score increased dementia conversion rate (OR 0.47, 95% CI 0.34-0.64). Alzheimer's disease was the main cause of dementia (79.8%). CONCLUSIONS: Memory impairment is a risk factor for future dementia in the neurologically-healthy elderly. This can be observed in a subgroup of subjects with SMI defined on the aMMSE delayed-recall subscore. Some other measurements should be added to the SMI construct to improve its predictive validity.

Cerebral hypoperfusion detected by SPECT in patients with systemic lupus erythematosus is related to clinical activity and cumulative tissue damage.

Cerebral single-photon emission computed tomography (SPECT) is a sensitive technique for the detection of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). The objective was to determine whether a relationship exists between cerebral hypoperfusion as detected by cerebral SPECT, cumulative tissue damage and the clinical activity of SLE. Cerebral technetium-99m-L,L-ethyl cysteinate dimer (99mTc-ECD) SPECT was performed in two groups of patients: 10 women with SLE (Group A) who had no previous history of major neuropsychiatric (NPS) manifestations and no minor NPS symptoms in the last six months, and 57 unselected women with SLE (Group B). In the same week that SPECT was performed, the SLE disease activity index (SLEDAI), SLICC/ACR damage index, native anti-DNA antibodies (ELISA) and erythrocyte sedimentation rate (ESR) were determined. In Group A, cerebral SPECT showed moderate or severe hypoperfusion (abnormal SPECT) in five patients without NPS symptoms, unrelated to age (mean 24.8 versus 27.8 years) or disease duration (mean 6.8 versus 9 years). Patients with significant cerebral hypoperfusion had greater clinical disease activity (mean SLEDAI 13.6 versus 7.6) (SLEDAI > 7 in 5/5 versus 1/5; Fisher: 0.023; OR: 33; 95% CI: 2.3-469.8) and ESR (mean 43.6 versus 9.8; P < 0.05). In Group B, the mean age of the 57 unselected women with SLE was 37 years (SD 6.3) and the mean duration of the disease was 9.7 years (SD 6.3). Cerebral SPECT revealed normal perfusion or mild hypoperfusion (normal SPECT) in 30 patients (52.6%), and moderate or severe hypoperfusion in 27 (47.4%). Hypoperfusion was unrelated to age, duration of SLE or concentrations of anti-DNA antibodies and C3 and C4 fractions. Patients with significant cerebral hypoperfusion had more active clinical disease (mean SLEDAI 13.92; SD 8.44 versus 4.56; SD 4.15) (Mann-Whitney, P < 0.005), more cumulative tissue damage (mean SLICC 2.66; SD 2.84 versus 1.03; SD 1.51) (Mann-Whitney, P = 0.035), and higher ESR values (mean 28.7; SD 22.5 versus 17.7; SD 13.3) (Mann-Whitney, P = 0.023) than patients with normal SPECT studies. Significant cerebral hypoperfusion was related both to NPS manifestations present at the time of the study (17 of 27, 63% versus 3 of 30, 10%) (OR: 15.3) and cumulative manifestations (19 of 27, 70.4% versus 8 of 30, 26.7%) (OR: 6.5), whether mild (OR: 5.5) or severe (OR: 8.2). In conclusion, cerebral hypoperfusion detected by SPECT in patients with SLE is related to clinical activity (SLEDAI), cumulative tissue damage (SLICC) and concomitant or previous NPS manifestations.