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

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

[Neurotransmitters in Alzheimer's disease]. / Neurotransmisores en la enfermedad de Alzheimer.

AIM: To review the current state of the art in neurotransmission in Alzheimer's disease (AD) and its involvement in the pathophysiology of the disease. INTRODUCTION: AD is a neurodegenerative disorder that is estimated to affect 15 million people around the world. Since the cholinergic hypothesis of AD was put forward 20 years ago, numerous studies have been conducted in an attempt to determine the role that neurotransmitters play in AD. Among other things, this has made it possible to develop drugs based on the inhibition of acetylcholinesterase. DEVELOPMENT: The monoaminergic neurotransmission systems are examined, with special attention given to the cholinergic system, and their anatomical distribution, function, receptors, activity and degradation systems are also described. Peptidergic neurotransmission systems are only briefly discussed, since they are not the main objective of this report. We also review the cholinergic hypothesis and the possible interrelations between cholinergic neurotransmission and beta-amyloid metabolism, as well as the potential involvement of acetylcholinesterase inhibitor drugs in more fundamental pathophysiological mechanisms, which act with a neuroprotective component.

Neurotransmisores en la enfermedad de Alzheimer / Neurotransmitters in Alzheimer’s disease

Objetivo. Revisar el estado actual de los conocimientos sobre la neurotransmisión en la enfermedad de Alzheimer (EA) y su implicación en la fisiopatología de la enfermedad. Introducción. La EA es un trastorno neurodegenerativo que se estima que afecta a 15 millones de personas en todo el mundo. Desde que se postuló hace 20 años la hipótesis colinérgica de la EA, se han realizado múltiples estudios para intentar conocer el papel que desempeñan los neurotransmisores en la EA. Entre otras cosas, esto ha permitido el desarrollo de fármacos basados en la inhibición de la acetilcolinesterasa. Desarrollo. Se revisan los sistemas de neurotransmisión monoaminérgicos, con especial atención en el sistema colinérgico, describiendo su distribución anatómica, función, receptores, actividad y sistemas de degradación. Se citan brevemente, ya que no es el objetivo primario de esta revisión, los sistemas de neurotransmisión peptidérgicos y se revisan la hipótesis colinérgica y las posibles interrelaciones entre la neurotransmisión colinérgica y el metabolismo del b-amiloide, así como la posible implicación de los fármacos inhibidores de la acetilcolinesterasa en mecanismos fisiopatológicos más básicos, con un componente neuroprotector (AU)

Aim. To review the current state of the art in neurotransmission in Alzheimer’s disease (AD) and its involvement in the pathophysiology of the disease. Introduction. AD is a neurodegenerative disorder that is estimated to affect 15 million people around the world. Since the cholinergic hypothesis of AD was put forward 20 years ago, numerous studies have been conducted in an attempt to determine the role that neurotransmitters play in AD. Among other things, this has made it possible to develop drugs based on the inhibition of acetylcholinesterase. Development. The monoaminergic neurotransmission systems are examined, with special attention given to the cholinergic system, and their anatomical distribution, function, receptors, activity and degradation systems are also described. Peptidergic neurotransmission systems are only briefly discussed, since they are not the main objective of this report. We also review the cholinergic hypothesis and the possible interrelations between cholinergic neurotransmission and β-amyloid metabolism, as well as the potential involvement of acetylcholinesterase inhibitor drugs in more fundamental pathophysiological mechanisms, which act with a neuroprotective component (AU)

[Values of GERMCIDE neuropsychological protocol in a sample of normal subjects]. / Valores del protocolo neuropsicológico GERMCIDE en una muestra de sujetos normales.

INTRODUCTION: The diagnosis of patients with cognitive deterioration or dementia requires a global approach in which the neuropsychological examination is a key piece. As part of the GERMCIDE study (Group for the Study and Multicenter Registry of Incident Cases of Dementia in Spain), a protocol was designed that included an assessment of the different cognitive functions that are most frequently altered in dementias (memory, orientation, speech, praxis, abstraction capacity and executive function). METHODS: In order to obtain data in normal subjects, this neuropsychological protocol was applied to a group of persons over 50 years without cognitive deterioration or dementia. RESULTS: A total of 103 subjects whose ages ranged from 50 to 95 years (mean: 73.5; SD: 9.3 years); 39 (37.9%) men and 64 (62.1%) women were studied. The mean score on the Mini-Mental State Examination (MMSE) was 27/30 (SD: 2.0). In the speech and praxis tests, 90% of the subjects obtained the maximum value, while performances were more unequal in memory, reasoning and programming. Mean score, standard deviation and distribution in percentages for each subtest are presented. CONCLUSIONS: The values obtained in this sample of normal subjects and their distribution in percentages may be very helpful to facilitate the interpretation of the findings of the neuropsychological examination with the GERMCIDE protocol in the general neurology clinic visits and also in the specialized visits in dementia.

Valores del protocolo neuropsicológico GERMCIDE en una muestra de sujetos normales / Values of GERMCIDE neuropsychological protocol in a sample of normal subjects

Introducción. El diagnóstico de los pacientes con deterioro cognitivo o demencia exige un enfoque global en el que la exploración neuropsicológica es una pieza clave. Como parte del estudio GERMCIDE (Grupo para el Estudio y Registro Multicéntrico de Casos Incidentes de Demencia en España) se diseñó un protocolo que incluye una valoración de las diferentes funciones cognitivas que con mayor frecuencia se alteran en las demencias (memoria, orientación, lenguaje, praxias, capacidad de abstracción y función ejecutiva). Métodos. Con el objetivo de obtener datos en sujetos normales este protocolo neuropsicológico se aplicó a un grupo de personas mayores de 50 años sin deterioro cognitivo ni demencia. Resultados. Se estudiaron 103 sujetos con edades comprendidas entre 50 y 95 años (media: 73,5; desviación estándar [DE]: '9,3 años); 39 (37,90J0) hombres y 64 (62,1 %) mujeres. La puntuación media en el Mini-Mental State Examination (MMSE) fue de 27/30 (DE: 2,0). En las pruebas de lenguaje y praxias el 900J0 de los sujetos obtuvieron el valor máximo, mientras que en memoria, razonamiento y programación los rendimientos fueron más dispares. Se presenta la puntuación media, DE y distribución en percentiles para cada subtest. Conclusiones. Los valores obtenidos en esta muestra de sujetos normales y su distribución en percentiles pueden ser de gran ayuda para facilitar la interpretación de los hallazgos de la exploración neuropsicológica con el protocolo GERMCIDE en las consultas de neurología general y también en las consultas especializadas en demencia

Introduction. The diagnosis of patients with cognitive deterioration or dementia requires a global approach in which the neuropsychological examination is a key piece. As part of the GERMCIDE study (Group for the Study and Multicenter Registry of Incident Cases of Dementia in Spain), a protocol was designed that included an assessment of the different cognitive functions that are most frequently altered in dementias (memory, orientation, speech, praxis, abstraction capacity and executive function). Methods. In order to obtain data in normal subjects, this neuropsychological protocol was applied to a group of persons over 50 years without cognitive deterioration or dementia. Results. A total of 103 subjects whose ages ranged from 50 to 95 years (mean: 73.5; SD: 9.3 years); 39 (37.9%) men and 64 (62.1%) women were studied. The mean score on the Mini-Mental State Examination (MMSE) was 27/30 (SD: 2.0). In the speech and praxis tests, 90% of the subjects obtained the maximum value, while performances were more unequal in memory, reasoning and programming. Mean score, standard deviation and distribution in percentages for each subtest are presented. Conclusions. The values obtained in this sample of normal subjects and their distribution in percentages may be very helpful to facilitate the interpretation of the findings of the neuropsychological examination with the GERMCIDE protocol in the general neurology clinic visits and also in the specialized visits in dementia

New V272A presenilin 1 mutation with very early onset subcortical dementia and parkinsonism.

In this report, we present the clinical and pathological details of a kindred of four individuals with a novel missense mutation (V272A) of the presenilin 1 gene (PSEN1) that experienced a subcortical dementia. The age of onset of symptoms ranged 26-36-year old, with an age at death of 36-46 years. Initial symptom was a marked mood disorder, with prominent parkinsonism in one case. The neuropsychological study, as well as the neuroimaging and PET in the proband were concordant with a subcortical dementia. The cerebral pathology showed in this patient, aside from the classical lesions of Alzheimer disease, Lewy bodies in cortex and substantia nigra, and widespread subcortical neuritic lesions. This clinical pattern and pathology expands the clinical spectrum of familial Alzheimer's disease and compel to include mutations of PSEN1 gene in the genetic study of subcortical dementia.

Wheat germ agglutinin-binding glycoproteins are decreased in Alzheimer's disease cerebrospinal fluid.

A number of biomarkers (e.g. Abeta, tau) has been identified in Alzheimer's disease CSF. However, none fulfils the criteria of sensitivity and specificity (> 80%) needed for the development of an accurate diagnostic test. The lack of a suitable marker has prompted the search for new CSF biomarkers. In this study, the glycosylation of CSF proteins was examined using lectin blotting. Lumbar CSF was collected ante mortem from 22 non-Alzheimer's disease and 12 probable Alzheimer's disease cases and ventricular CSF collected post mortem from 7 non-Alzheimer's disease and 16 Alzheimer's disease cases confirmed by pathologic examination. When CSF glycoproteins were stained with wheat germ agglutinin (WGA), the staining intensity was found to be significantly lower in the Alzheimer's disease group. No difference in staining was found using other lectins (Canavalia ensiformis agglutinin, Ricinus communis agglutinin, Lens culinaris agglutinin). The measurement of WGA-reactive glycoproteins in CSF may be a useful biomarker for diagnosis of Alzheimer's disease.

Altered glycosylation of acetylcholinesterase in lumbar cerebrospinal fluid of patients with Alzheimer's disease.

As clinical diagnosis of Alzheimer's disease is only 80%-90% accurate, there is a need to identify biochemical markers of Alzheimer's disease. Previous studies have shown an abnormality in the glycosylation of acetylcholinesterase (AChE) in the CSF collected postmortem from patients with Alzheimer's disease. This abnormality was very specific for Alzheimer's disease, as it was not detected in other illnesses causing dementia. We report here that the glycosylation of AChE is also altered in lumbar CSF collected antemortem. The altered glycosylation was due to increased concentrations of a minor AChE isoform that does not bind to concanavalin A (Con A). Glycosylation of AChE may eventually be of diagnostic value, especially when used in combination with other CSF markers.

Application of a Spanish version of the "Informant Questionnaire on Cognitive Decline in the Elderly" in the clinical assessment of dementia.

We studied the validity of a complete (S-IQCODE) and a shortened (SS- IQCODE) Spanish version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia in a clinical setting. Fifty-three consecutive outpatients were assessed with an extensive workup and followed up for 6 months in a specialized clinic for the diagnosis and management of dementia. Thirty eight (71%) were finally diagnosed as demented. The Mini-Mental State Examination (MMSE) had a slightly greater diagnostic power than did the S-IQCODE and the SS-IQCODE (sensitivity 89% vs. 84% and 79%; specificity 80% vs. 73% for both; positive predictive value 92% vs. 89% and 88%; negative predictive value 75% vs. 65% and 58%), but without statistical significance. Both the S-IQCODE and SS-IQCODE were independent of previous education of the patients. The best diagnostic results were obtained when the cognitive scores of the patient in the MMSE and the report of the relative in the S-IQCODE were simultaneously considered. We conclude that the IQCODE, in a complete as well as in a shortened form, is a good diagnostic instrument in the clinical setting that can enhance the validity of other cognitive tests.

Oxidative polymorphism of debrisoquine is not related to the risk of Alzheimer's disease.

Oxidative polymorphism of debrisoquine has been studied in patients suffering from many spontaneous disorders which show genetic and/or environmental factors in their pathogenesis. To elucidate whether any relationship exists between this genetic polymorphism and the risk of developing Alzheimer disease (AD) we determined the oxidative phenotype and metabolic ratio (MR) of debrisoquine (DBQ) in 47 patients with AD or senile dementia of Alzheimer type (SDAT) and 837 healthy controls. The patients were free of drugs during at least the previous 30 days; all the controls were free of drugs. Three patients (6.38%) and 42 controls (5.02%) were classified as poor metabolizers (PM) of DBQ (non-significant difference). The distribution of MR values in the AD/SDAT patients showed non-significant differences when compared with controls. There was no relation between oxidative polymorphism of DBQ and age at onset of the disease. These results suggest that DBQ oxidative genetic polymorphism cannot be considered as a risk factor for developing AD-SDAT.

Acetylator polymorphism in Alzheimer's disease.

OBJECTIVES: To elucidate whether any relationship exists between genetic acetylator polymorphism and the risk of developing Alzheimer's disease. METHODS: Acetylator polymorphism has been determined, using sulphamethazine, in 54 patients with Alzheimer's disease or senile dementia of Alzheimer type and in 93 age-matched controls. RESULTS: Thirty-one patients (57.4%) and 54 controls (58%) were classified as slow acetylators (non-significant difference). No relation was found between acetylator polymorphism and age at onset of disease and scores of Minimental examination and Blessed, Tomlinson & Roth scale in the group of patients with Alzheimer's disease/senile dementia of Alzheimer type. CONCLUSIONS: Our results do not support the existence of any relationship between acetylator polymorphism and the risk of developing Alzheimer type dementia.

Hereditary branchial myoclonus with spastic paraparesis and cerebellar ataxia: a new autosomal dominant disorder.

We report a family with branchial myoclonus, spastic paraparesis, and cerebellar ataxia in which six members were affected in two generations and the inheritance appeared to be autosomal dominant. Age at onset ranged from 40 to 50 years. Rhythmic myoclonus involving the palate, pharynx, larynx, and face was followed by truncal ataxia and spastic paraparesis in most patients. CT and MRI revealed mild atrophy of the cerebral and cerebellar cortex and severe atrophy of the medulla and spinal cord. The pons appeared normal and the olives not hypertrophic. CSF studies revealed severe reduction of the serotonin metabolite 5-hydroxyindoleacetic acid. Treatment with 5-hydroxytryptophan and carbidopa at highest tolerated dose mildly improved ataxia but did not modify the myoclonus. Treatment with anticholinergics, benzodiazepines, phenytoin, valproate, carbamazepine, and baclofen was unsuccessful. The clinical symptoms were progressive, leading to death or severe disability 5 to 10 years after the onset of the disease.