Degenerative dementias: a question of syndrome or disease?

BACKGROUND: Neurologists refer to numerous "syndromes," consisting of specific combinations of clinical manifestations, following a specific progression pattern, and with the support of blood analysis (without genomic-proteomic parameters) and neuroimaging findings (MRI, CT, perfusion SPECT, or 18F-FDG-PET scans). Neurodegenerative "diseases," on the other hand, are defined by specific combinations of clinical signs and histopathological findings; these must be confirmed by a clinical examination and a histology study or evidence of markers of a specific disorder for the diagnosis to be made. However, we currently know that most genetic and histopathological alterations can result in diverse syndromes. The genetic or histopathological aetiology of each syndrome is also heterogeneous, and we may encounter situations with pathophysiological alterations characterising more than one neurodegenerative disease. Sometimes, specific biomarkers are detected in the preclinical stage. DEVELOPMENT: We performed a literature review to identify patients whose histopathological or genetic disorder was discordant with that expected for the clinical syndrome observed, as well as patients presenting multiple neurodegenerative diseases, confirming the heterogeneity and overlap between syndromes and diseases. We also observed that the treatments currently prescribed to patients with neurodegenerative diseases are symptomatic. CONCLUSIONS: Our findings show that the search for disease biomarkers should be restricted to research centres, given the lack of disease-modifying drugs or treatments improving survival. Moreover, syndromes and specific molecular or histopathological alterations should be managed independently of one another, and new "diseases" should be defined and adapted to current knowledge and practice.

Demencias degenerativas: ¿un dilema de síndromes o de enfermedades? / Degenerative dementias: A question of syndrome or disease?

Introducción: En neurología cognitiva se identifican múltiples «síndromes», consistentes en combinaciones específicas de manifestaciones clínicas, con una evolución determinada y con el apoyo de un análisis de sangre (sin parámetros de genómica-proteómica) y pruebas de neuroimagen (TAC, resonancia, SPECT de perfusión, PET con 18F-fluorodesoxiglucosa). Por otra parte, las «enfermedades» neurodegenerativas demenciantes representan combinaciones clínico-histopatológicas concretas, cuya presencia debe comprobarse en la exploración del enfermo, junto con un estudio histológico o evidencia de marcadores del trastorno molecular específico. No obstante, actualmente se sabe que la manifestación sindrómica de cada alteración histopatológica o genética es variada, que el sustrato histopatológico o genético de cada síndrome también lo es y que a veces coexisten alteraciones fisiopatológicas de más de una enfermedad neurodegenerativa. Además, ocasionalmente se detectan biomarcadores específicos en la fase preclínica. Desarrollo: Tras realizar una búsqueda bibliográfica de casos con alteración histopatológica o genética discordante con la esperada para el síndrome observado, y de casos con coexistencia de enfermedades degenerativas, resulta evidente la heterogeneidad y el solapamiento entre síndromes y enfermedades neurodegenerativas. Además, en la revisión se comprueba que los tratamientos que se prescriben a pacientes con enfermedades degenerativas son sintomáticos. Conclusiones: De la revisión se desprende que mientras no existan tratamientos modificadores de la progresión o la supervivencia, la búsqueda de marcadores de enfermedad debe quedar reservada a centros investigadores. Además, deberían manejarse de modo independiente los síndromes y las alteraciones moleculares e histopatológicas específicas, con definición de nuevas «enfermedades», adaptada a los conocimientos y a la práctica actuales. (AU)

Background: Neurologists refer to numerous “syndromes,‿ consisting of specific combinations of clinical manifestations, following a specific progression pattern, and with the support of blood analysis (without genomic-proteomic parameters) and neuroimaging findings (MRI, CT, perfusion SPECT, or 18F-FDG-PET scans). Neurodegenerative “diseases,‿ on the other hand, are defined by specific combinations of clinical signs and histopathological findings; these must be confirmed by a clinical examination and a histology study or evidence of markers of a specific disorder for the diagnosis to be made. However, we currently know that most genetic and histopathological alterations can result in diverse syndromes. The genetic or histopathological aetiology of each syndrome is also heterogeneous, and we may encounter situations with pathophysiological alterations characterising more than one neurodegenerative disease. Sometimes, specific biomarkers are detected in the preclinical stage. Development: We performed a literature review to identify patients whose histopathological or genetic disorder was discordant with that expected for the clinical syndrome observed, as well as patients presenting multiple neurodegenerative diseases, confirming the heterogeneity and overlap between syndromes and diseases. We also observed that the treatments currently prescribed to patients with neurodegenerative diseases are symptomatic. Conclusions: Our findings show that the search for disease biomarkers should be restricted to research centres, given the lack of disease-modifying drugs or treatments improving survival. Moreover, syndromes and specific molecular or histopathological alterations should be managed independently of one another, and new “diseases‿ should be defined and adapted to current knowledge and practice. (AU)

Degenerative dementias: A question of syndrome or disease? / Demencias degenerativas: ¿un dilema de síndromes o de enfermedades?

BACKGROUND: Neurologists refer to numerous "syndromes," consisting of specific combinations of clinical manifestations, following a specific progression pattern, and with the support of blood analysis (without genomic-proteomic parameters) and neuroimaging findings (MRI, CT, perfusion SPECT, or 18F-FDG-PET scans). Neurodegenerative "diseases," on the other hand, are defined by specific combinations of clinical signs and histopathological findings; these must be confirmed by a clinical examination and a histology study or evidence of markers of a specific disorder for the diagnosis to be made. However, we currently know that most genetic and histopathological alterations can result in diverse syndromes. The genetic or histopathological aetiology of each syndrome is also heterogeneous, and we may encounter situations with pathophysiological alterations characterising more than one neurodegenerative disease. Sometimes, specific biomarkers are detected in the preclinical stage. DEVELOPMENT: We performed a literature review to identify patients whose histopathological or genetic disorder was discordant with that expected for the clinical syndrome observed, as well as patients presenting multiple neurodegenerative diseases, confirming the heterogeneity and overlap between syndromes and diseases. We also observed that the treatments currently prescribed to patients with neurodegenerative diseases are symptomatic. CONCLUSIONS: Our findings show that the search for disease biomarkers should be restricted to research centres, given the lack of disease-modifying drugs or treatments improving survival. Moreover, syndromes and specific molecular or histopathological alterations should be managed independently of one another, and new "diseases" should be defined and adapted to current knowledge and practice.

Nueva observación de la protección relativa que las enfermedades neurodegenerativas y el cáncer se confieren entre sí / New evidence of the relative protective effects of neurodegenerative diseases and cancer against each other

Introducción: El cáncer y las enfermedades degenerativas constituyen trastornos con algunos mecanismos compartidos que actúan en sentido opuesto, produciendo un fenómeno incontrolado de proliferación o pérdida de células. Observaciones diversas apuntan que los pacientes con enfermedad de Alzheimer tienen menor riesgo de desarrollar tumores y viceversa. En este artículo se expone la prevalencia de tumores (activos o superados) en pacientes de neurología cognitiva con y sin una enfermedad degenerativa demenciante. Pacientes y método: En 1.164 pacientes se analizó la frecuencia y topografía de tumores y la presencia o ausencia de enfermedad neurodegenerativa, que se clasificó en 4 grupos (enfermedad de Alzheimer, sinucleinopatía, enfermedad del complejo Pick y del complejo de poliglutamina). Se comparó la frecuencia de tumor en los subgrupos con y sin enfermedad degenerativa, y de esta en los pacientes con y sin trastorno tumoral. Resultados: Se registró proceso tumoral en el 12,1% de los pacientes con enfermedad neurodegenerativa y en el 17,3% del resto del grupo. En el grupo del estudio, un 14,8% de los que tienen antecedente tumoral fue diagnosticado de enfermedad neurodegenerativa, frente al 20,8% entre los que no tienen ese antecedente. Estas diferencias y las observadas en la comparación de subgrupos (tipo de enfermedad degenerativa y topografía del tumor) no alcanzaron significación estadística, excepto al contrastar enfermedades neurodegenerativas con tumores del sistema nervioso central y sinucleinopatías con neoplasias. Conclusiones: Las enfermedades neoplásicas y las neurodegenerativas demenciantes no son excluyentes, aunque muestran menor asociación de la esperada por su respectiva prevalencia

Background: Cancer and degenerative diseases share some pathogenic mechanisms which act in opposition to one another to produce either uncontrolled cell proliferation or cell death. According to several studies, patients with Alzheimer disease have a lower risk of neoplasia, and vice versa. This study describes the prevalence of tumours (active or successfully treated) in a series of patients with and without a dementing degenerative disease treated at a cognitive neurology unit. Patients and method: We analysed the frequency and topography of tumours and the presence or absence of a neurodegenerative disease in a group of 1,164 patients. Neurodegenerative diseases were classified in 4 groups: Alzheimer disease, synucleinopathies, Pick complex, and polyglutamine complex. We subsequently compared tumour frequency in patients with and without a degenerative disease, and prevalence of neurodegenerative diseases in patients with and without tumours. Results: Tumours were detected in 12.1% of the patients with a neurodegenerative disease and in 17.3% of the remaining patients. Around 14.8% of the patients with a history of neoplasia and 20.8% of the patients with no history of neoplasia were diagnosed with a neurodegenerative disease. Except for these differences and the differences between subgroups (type of degenerative disease and tumour location) were not statistically significant, except when comparing neurodegenerative diseases to central nervous system tumours, and synucleinopathies to neoplasms. Conclusion: Dementing degenerative diseases and neoplastic disorders are not mutually exclusive. Nevertheless, the rate of co-occurrence is lower than would be expected given the prevalence rate for each group

New evidence of the relative protective effects of neurodegenerative diseases and cancer against each other. / Nueva observación de la protección relativa que las enfermedades neurodegenerativas y el cáncer se confieren entre sí.

BACKGROUND: Cancer and degenerative diseases share some pathogenic mechanisms which act in opposition to one another to produce either uncontrolled cell proliferation or cell death. According to several studies, patients with Alzheimer disease have a lower risk of neoplasia, and vice versa. This study describes the prevalence of tumours (active or successfully treated) in a series of patients with and without a dementing degenerative disease treated at a cognitive neurology unit. PATIENTS AND METHOD: We analysed the frequency and topography of tumours and the presence or absence of a neurodegenerative disease in a group of 1,164 patients. Neurodegenerative diseases were classified in 4 groups: Alzheimer disease, synucleinopathies, Pick complex, and polyglutamine complex. We subsequently compared tumour frequency in patients with and without a degenerative disease, and prevalence of neurodegenerative diseases in patients with and without tumours. RESULTS: Tumours were detected in 12.1% of the patients with a neurodegenerative disease and in 17.3% of the remaining patients. Around 14.8% of the patients with a history of neoplasia and 20.8% of the patients with no history of neoplasia were diagnosed with a neurodegenerative disease. Except for these differences and the differences between subgroups (type of degenerative disease and tumour location) were not statistically significant, except when comparing neurodegenerative diseases to central nervous system tumours, and synucleinopathies to neoplasms. CONCLUSION: Dementing degenerative diseases and neoplastic disorders are not mutually exclusive. Nevertheless, the rate of co-occurrence is lower than would be expected given the prevalence rate for each group.

Alucinaciones auditivas en neurología cognitiva / Auditory hallucinations in cognitive neurology

Introducción: Los tinnitus y las alucinaciones verbales o musicales (AVM) pueden deberse a lesiones neurológicas de naturaleza y topografía diversa. Método: Se han rastreado estos síntomas en 1.000 pacientes de una consulta de neurología cognitiva, anotando datos epidemiológicos y de neuroimagen. Resultados: Refirieron tinnitus el 6,9% y AVM el 0,9%. Hubo predominio femenino no significativo en el grupo con paracusias. La edad media fue menor en los pacientes con tinnitus y mayor en los que tenían AVM. La hipoacusia mostró mayor prevalencia en los enfermos con paracusias (significativo con AVM). No hubo diferencias en la prevalencia de trastorno psicótico u obsesivo-compulsivo, o de leucoaraiosis. El tratamiento con ácido acetilsalicílico mostró mayor frecuencia en el grupo con AVM, y otros analgésicos no opioides y benzodiacepinas en los pacientes con tinnitus. La presunta causa de las AVM fue demencia con cuerpos de Lewy (n = 2, uno con enfermedad vascular), enfermedad de Alzheimer (n = 2, uno con enfermedad vascular), enfermedad vascular cerebral pura (n = 3), lesión cerebral traumática (n = 1) y lesión quirúrgica en el tronco encefálico (n = 1). En los 9 casos había un elemento facilitador de la aparición de paracusias, como hipoacusia (n = 6) o medicación de riesgo (n = 9), además de polifarmacia (n = 9). Conclusiones: Los pacientes con tinnitus tomaban con frecuencia benzodiacepinas y analgésicos no opioides, y en los que tenían AVM había mayor prevalencia de hipoacusia y de tratamiento con ácido acetilsalicílico. Las causas de AVM fueron demencia con cuerpos de Lewy, enfermedad de Alzheimer y lesiones focales en mesencéfalo, protuberancia, lóbulo temporal izquierdo o claustro izquierdo (AU)

Introduction: Different types and localisations of neurological lesions can produce tinnitus and verbal or musical hallucinations (VMH). Method: These symptoms were screened for in 1,000 outpatients at a cognitive neurology clinic, and epidemiological and neuroimaging data were recorded. Results: Tinnitus was present in 6.9% of the total and VMH in 0.9%. The paracusia group was predominantly female but the difference was not statistically significant. Patients with tinnitus were younger and those with VMH were older than the rest of the sample (mean ages). Hearing loss was more prevalent in the paracusia group (difference was significant in VMH subgroup). There were no intergroup differences in the prevalence of psychotic and obsessive-compulsive disorders, or of leukoaraiosis. Treatment with acetylsalicylic acid was more frequent in the VMH group, whereas other non-opioid analgesics and benzodiazepines were more commonly prescribed to patients with tinnitus. The suspected cause of VMH was dementia with Lewy bodies (n = 2, one with vascular disease), Alzheimer disease (n=2, one with vascular disease), isolated cerebrovascular disease (n = 3), traumatic brain injury (n = 1), and surgical brainstem lesion (n = 1). All VMH cases displayed an underlying factor that might prompt this symptom, eg, hearing loss (n = 6), a predisposing drug (n = 9), and polypharmacy (n = 9). Conclusions: Treatment with benzodiazepines and non-opioid analgesics was more frequent in the tinnitus group, whereas the VMH group showed a higher prevalence of hearing loss and treatment with acetylsalicylic acid. The causes of VMH were dementia with Lewy bodies, Alzheimer disease, and focal lesions in the mesencephalon, pons, left temporal lobe, or left claustrum (AU)

Síntomas conductuales y psiquiátricos en neurología cognitiva / Behavioural and psychiatric symptoms in cognitive neurology

Los síntomas conductuales y psiquiátricos (SCP) son frecuentes en el enfermo neurológico, contribuyen a producir discapacidad y reducen la calidad de vida. Se ha observado, en pacientes de neurología cognitiva, la prevalencia y tipo de SCP y su asociación con diagnósticos, regiones cerebrales o tratamientos específicos. Método. Análisis retrospectivo de 843 pacientes consecutivos de neurología cognitiva, revisando SCP, diagnóstico, alteración sensorial, topografía lesional en neuroimagen y tratamiento. Se contempló el total y se comparó el grupo de pacientes con deterioro cognitivo objetivo (n = 607) y sin deterioro. Resultados. Hubo SCP en el 59,9% de los pacientes (61,3% en los deteriorados y 56,4% en el resto). Un 31,1% tenía un SCP, 17,4% dos y 11,4% más de dos. Los SCP son más frecuentes en mujeres, sobre todo depresión y ansiedad. En los mayores de 64 años predominan los síntomas psicóticos y conductuales, y en los menores de 65 la ansiedad. Las personas con alteración sensorial tienen más síntomas psicóticos. Se aprecian más síntomas conductuales y psicóticos en personas con demencia degenerativa, depresión y ansiedad en las que tienen enfermedad psiquiátrica o efecto nocivo de sustancias, labilidad emocional en relación con trastorno metabólico u hormonal, hipocondría en los síndromes dolorosos e irritabilidad en la hipoxia crónica. Hay más alteraciones de la conducta en pacientes con anomalía en lóbulos frontales o temporal o parietal derechos, y se tratan preferentemente con antipsicóticos. Aparte de los tratamientos estándar, se observó asociación de distimia con opioides, betahistina y estatinas, y síntomas psicóticos con levodopa, piracetam y vasodilatadores

Behavioural and psychiatric symptoms (BPS) are frequent in neurological patients, contribute to disability, and decrease quality of life. We recorded BPS prevalence and type, as well as any associations with specific diagnoses, brain regions, and treatments, in consecutive outpatients examined in a cognitive neurology clinic. Method. A retrospective analysis of 843 consecutive patients was performed, including a review of BPS, diagnosis, sensory impairment, lesion topography (neuroimaging), and treatment. The total sample was considered, and the cognitive impairment (CI) group (n = 607) was compared to the non-CI group. Results. BPS was present in 59.9% of the patients (61.3% in the CI group, 56.4% in the non-CI group). One BPS was present in 31.1%, two in 17.4%, and three or more in 11.4%. BPS, especially depression and anxiety, are more frequent in women than in men. Psychotic and behavioural symptoms predominate in subjects aged 65 and older, and anxiety in those younger than 65. Psychotic symptoms appear more often in patients with sensory impairment. Psychotic and behavioural symptoms are more prevalent in patients with degenerative dementia; depression and anxiety in those who suffer a psychiatric disease or adverse effects of substances; emotional lability in individuals with a metabolic or hormonal disorder; hypochondria in those with a pain syndrome; and irritability in subjects with chronic hypoxia. Behavioural symptoms are more frequent in patients with anomalies in the frontal or right temporal or parietal lobes, and antipsychotics constitute the first line of treatment. Leaving standard treatments aside, associations were observed between dysthymia and opioid analgesics, betahistine and statins, and between psychotic symptoms and levodopa, piracetam, and vasodilators

Behavioural and psychiatric symptoms in cognitive neurology. / Síntomas conductuales y psiquiátricos en neurología cognitiva.

Behavioural and psychiatric symptoms (BPS) are frequent in neurological patients, contribute to disability, and decrease quality of life. We recorded BPS prevalence and type, as well as any associations with specific diagnoses, brain regions, and treatments, in consecutive outpatients examined in a cognitive neurology clinic. METHOD: A retrospective analysis of 843 consecutive patients was performed, including a review of BPS, diagnosis, sensory impairment, lesion topography (neuroimaging), and treatment. The total sample was considered, and the cognitive impairment (CI) group (n=607) was compared to the non-CI group. RESULTS: BPS was present in 59.9% of the patients (61.3% in the CI group, 56.4% in the non-CI group). One BPS was present in 31.1%, two in 17.4%, and three or more in 11.4%. BPS, especially depression and anxiety, are more frequent in women than in men. Psychotic and behavioural symptoms predominate in subjects aged 65 and older, and anxiety in those younger than 65. Psychotic symptoms appear more often in patients with sensory impairment. Psychotic and behavioural symptoms are more prevalent in patients with degenerative dementia; depression and anxiety in those who suffer a psychiatric disease or adverse effects of substances; emotional lability in individuals with a metabolic or hormonal disorder; hypochondria in those with a pain syndrome; and irritability in subjects with chronic hypoxia. Behavioural symptoms are more frequent in patients with anomalies in the frontal or right temporal or parietal lobes, and antipsychotics constitute the first line of treatment. Leaving standard treatments aside, associations were observed between dysthymia and opioid analgesics, betahistine and statins, and between psychotic symptoms and levodopa, piracetam, and vasodilators.

Auditory hallucinations in cognitive neurology. / Alucinaciones auditivas en neurología cognitiva.

INTRODUCTION: Different types and localisations of neurological lesions can produce tinnitus and verbal or musical hallucinations (VMH). METHOD: These symptoms were screened for in 1,000 outpatients at a cognitive neurology clinic, and epidemiological and neuroimaging data were recorded. RESULTS: Tinnitus was present in 6.9% of the total and VMH in 0.9%. The paracusia group was predominantly female but the difference was not statistically significant. Patients with tinnitus were younger and those with VMH were older than the rest of the sample (mean ages). Hearing loss was more prevalent in the paracusia group (difference was significant in VMH subgroup). There were no intergroup differences in the prevalence of psychotic and obsessive-compulsive disorders, or of leukoaraiosis. Treatment with acetylsalicylic acid was more frequent in the VMH group, whereas other non-opioid analgesics and benzodiazepines were more commonly prescribed to patients with tinnitus. The suspected cause of VMH was dementia with Lewy bodies (n=2, one with vascular disease), Alzheimer disease (n=2, one with vascular disease), isolated cerebrovascular disease (n=3), traumatic brain injury (n=1), and surgical brainstem lesion (n=1). All VMH cases displayed an underlying factor that might prompt this symptom, eg, hearing loss (n=6), a predisposing drug (n=9), and polypharmacy (n=9). CONCLUSIONS: Treatment with benzodiazepines and non-opioid analgesics was more frequent in the tinnitus group, whereas the VMH group showed a higher prevalence of hearing loss and treatment with acetylsalicylic acid. The causes of VMH were dementia with Lewy bodies, Alzheimer disease, and focal lesions in the mesencephalon, pons, left temporal lobe, or left claustrum.

Prescripciones inconvenientes en el tratamiento del paciente con deterioro cognitivo / Inappropriate treatments for patients with cognitive decline

Introducción: Algunos fármacos resultan inconvenientes en pacientes con deterioro cognitivo. Se analiza su uso en 500 pacientes y se revisa la bibliografía. Desarrollo: Las benzodiacepinas producen dependencia y reducen la atención, memoria y agilidad motora. Pueden inducir desinhibición o agresividad, facilitan los episodios confusionales e incrementan los accidentes y la mortalidad en mayores de 60 años. En mayores de 65, la presión sistólica baja se asocia a deterioro cognitivo. Es recomendable mantenerla en 130-140 mmHg (145 en ≥ 80 años). La colesterolemia < 160 mg/dl se asocia a mayor morbimortalidad, agresividad y suicidio, y el colesterol unido a las lipoproteínas de alta densidad (c-HDL) < 40 mg/dl empeora la memoria y aumenta el riesgo vascular y la mortalidad. La edad avanzada predispone para que los opioides produzcan alteración cognitiva y confusión. En demencias no Alzheimer y no asociadas a Parkinson, deterioro cognitivo ligero y enfermedades psiquiátricas, los efectos adversos de anticolinesterásicos y memantina probablemente superan al beneficio. La alteración cognitiva por anticolinérgicos de acción preferentemente periférica también es posible. Hay que conocer la demencia o psicosis por corticoides, y saber que la polifarmacia facilita el síndrome confusional. El 70,4% de 500 pacientes con disfunción cognitiva analizados recibía polifarmacia y el 42%, benzodiacepinas. Los que compartían ambas situaciones representaron el 74,3% de los casos en los que se sospechó iatrogenia. Conclusiones: En personas con edad avanzada o deterioro cognitivo, es necesario evitar la polifarmacia innecesaria y tener presente que las benzodiacepinas, los opioides y los anticolinérgicos producen frecuentemente alteraciones cognitivas y conductuales. Además, deben evitarse la presión sistólica < 130 mmHg, el colesterol < 160 mg/dl y el colesterol HDL < 40 mg/dl

Introduction: Some treatments are inappropriate for patients with cognitive decline. We analyse their use in 500 patients and present a literature review. Development: Benzodiazepines produce dependence, and reduce attention, memory, and motor ability. They can cause disinhibition or aggressive behaviour, facilitate the appearance of delirium, and increase accident and mortality rates in people older than 60. In subjects over 65, low systolic blood pressure is associated with cognitive decline. Maintaining this figure between 130 and 140 mm Hg (145 in patients older than 80) is recommended. Hypocholesterolaemia < 160 mg/dl is associated with increased morbidity and mortality, aggressiveness, and suicide; HDL-cholesterol < 40 mg/dl is associated with memory loss and increased vascular and mortality risks. Old age is a predisposing factor for developing cognitive disorders or delirium when taking opioids. The risks of prescribing anticholinesterases and memantine to patients with non-Alzheimer dementia that is not associated with Parkinson disease, mild cognitive impairment, or psychiatric disorders probably outweigh the benefits. Anticholinergic drugs acting preferentially on the peripheral system can also induce cognitive side effects. Practitioners should be aware of steroid-induced dementia and steroid-induced psychosis, and know that risk of delirium increases with polypharmacy. Of 500 patients with cognitive impairment, 70.4% were on multiple medications and 42% were taking benzodiazepines. Both conditions were present in 74.3% of all suspected iatrogenic cases. Conclusions: Polypharmacy should be avoided, if it is not essential, especially in elderly patients and those with cognitive impairment. Benzodiazepines, opioids and anticholinergics often elicit cognitive and behavioural disorders. Moreover, systolic blood pressure must be kept above 130 mm Hg, total cholesterol levels over 160 mg/dl, and HDL-cholesterol over 40 mg/dl in this population

Bradicardia en la demencia frontotemporal / Bradycardia in frontotemporal dementia

Introducción: Diversas áreas cerebrales, como la corteza orbitofrontal y frontomedial, la ínsula y la amígdala, intervienen en el control del sistema nervioso autónomo sobre funciones cardiovasculares como la frecuencia cardíaca. El proceso degenerativo de la demencia frontotemporal (DFT) involucra estas estructuras anatómicas y, por tanto, podría producir síntomas cardiovasculares disautonómicos. Objetivo: Observar si la bradicardia de origen cerebral es más frecuente en pacientes con DFT que en enfermos con deterioro cognitivo ligero o demencia de otra etiología. Pacientes y método: Una vez excluidos los pacientes con arritmia de origen cardíaco, se registró la frecuencia cardíaca de 258 pacientes con síntomas cognitivos (36 con DFT, 22 con enfermedad de Alzheimer, 23 con demencia vascular, 10 con otras demencias y 167 con deterioro cognitivo sin demencia). Resultados: La bradicardia (< 60 ppm) fue estadísticamente más frecuente en los pacientes con DFT. La diferencia se mantuvo significativa tras excluir a los que estaban en tratamiento con potencial efecto bradicardizante. La bradicardia fue más prevalente en la DFT conductual que en la DFT afásica, y hubo tendencia al predominio en los pacientes con mayor atrofia en el hemisferio derecho. La presión arterial sistólica de los pacientes con DFT fue inferior a la de los otros sujetos del estudio, y fue mayor la prevalencia de hipotensión sistólica (< 120 y < 100 mmHg). Conclusión: Se ha observado mayor frecuencia de bradicardia en los pacientes con DFT que en otros pacientes con síntomas cognitivos. Antes de considerar este dato semiológico como un signo de apoyo al diagnóstico de DFT, será necesario realizar nuevas observaciones

Introduction: Numerous regions of the brain, such as the medial frontal cortex, orbitofrontal cortex, insula, and amygdala, participate in the autonomic control of cardiovascular functions such as heart rate. The degenerative process in frontotemporal dementia (FTD) involves the listed anatomical structures and may therefore produce dysautonomic cardiovascular symptoms. Aim: To observe whether or not non-cardiogenic bradycardia was more frequent in a group of patients with FTD than in subjects with mild cognitive impairment or dementia of a different aetiology. Patients and method: Once patients with primary cardiac arrhythmia were excluded, we registered the heart rates of 258 patients with cognitive symptoms (36 with FTD, 22 with Alzheimer disease, 23 with vascular dementia, 10 with other dementias, and 167 with non-dementia cognitive impairment). Results: Bradycardia (< 60 beats/minute) was significantly more frequent in patients with FTD. This difference remained significant after excluding subjects undergoing treatment with a potentially bradycardic effect. Bradycardia was more prevalent in behavioural FTD cases than in cases of the aphasic variant, and we detected a trend toward higher frequency among patients with more pronounced right hemisphere atrophy. Moreover, mean systolic blood pressure in FTD patients was lower than in other participants, and systolic hypotension (< 120 and < 100 mm Hg) was more prevalent. Conclusion: Bradycardia was more frequent in the FTD sample than in other patients with cognitive symptoms. Further investigations will be necessary before we may consider bradycardiato be a sign supporting diagnosis of FTD or its behavioural variant

Bradycardia in frontotemporal dementia.

INTRODUCTION: Numerous regions of the brain, such as the medial frontal cortex, orbitofrontal cortex, insula, and amygdala, participate in the autonomic control of cardiovascular functions such as heart rate. The degenerative process in frontotemporal dementia (FTD) involves the listed anatomical structures and may therefore produce dysautonomic cardiovascular symptoms. AIM: To observe whether or not non-cardiogenic bradycardia was more frequent in a group of patients with FTD than in subjects with mild cognitive impairment or dementia of a different aetiology. PATIENTS AND METHOD: Once patients with primary cardiac arrhythmia were excluded, we registered the heart rates of 258 patients with cognitive symptoms (36 with FTD, 22 with Alzheimer disease, 23 with vascular dementia, 10 with other dementias, and 167 with non-dementia cognitive impairment). RESULTS: Bradycardia (<60 beats/minute) was significantly more frequent in patients with FTD. This difference remained significant after excluding subjects undergoing treatment with a potentially bradycardic effect. Bradycardia was more prevalent in behavioural FTD cases than in cases of the aphasic variant, and we detected a trend toward higher frequency among patients with more pronounced right hemisphere atrophy. Moreover, mean systolic blood pressure in FTD patients was lower than in other participants, and systolic hypotension (<120 and <100mm Hg) was more prevalent. CONCLUSION: Bradycardia was more frequent in the FTD sample than in other patients with cognitive symptoms. Further investigations will be necessary before we may consider bradycardia to be a sign supporting diagnosis of FTD or its behavioural variant.

Inappropriate treatments for patients with cognitive decline.

INTRODUCTION: Some treatments are inappropriate for patients with cognitive decline. We analyse their use in 500 patients and present a literature review. DEVELOPMENT: Benzodiazepines produce dependence, and reduce attention, memory, and motor ability. They can cause disinhibition or aggressive behaviour, facilitate the appearance of delirium, and increase accident and mortality rates in people older than 60. In subjects over 65, low systolic blood pressure is associated with cognitive decline. Maintaining this figure between 130 and 140 mm Hg (145 in patients older than 80) is recommended. Hypocholesterolaemia < 160 mg/dl is associated with increased morbidity and mortality, aggressiveness, and suicide; HDL-cholesterol<40 mg/dl is associated with memory loss and increased vascular and mortality risks. Old age is a predisposing factor for developing cognitive disorders or delirium when taking opioids. The risks of prescribing anticholinesterases and memantine to patients with non-Alzheimer dementia that is not associated with Parkinson disease, mild cognitive impairment, or psychiatric disorders probably outweigh the benefits. Anticholinergic drugs acting preferentially on the peripheral system can also induce cognitive side effects. Practitioners should be aware of steroid-induced dementia and steroid-induced psychosis, and know that risk of delirium increases with polypharmacy. Of 500 patients with cognitive impairment, 70.4% were on multiple medications and 42% were taking benzodiazepines. Both conditions were present in 74.3% of all suspected iatrogenic cases. CONCLUSIONS: Polypharmacy should be avoided, if it is not essential, especially in elderly patients and those with cognitive impairment. Benzodiazepines, opioids and anticholinergics often elicit cognitive and behavioural disorders. Moreover, systolic blood pressure must be kept above 130 mm Hg, total cholesterol levels over 160 mg/dl, and HDL-cholesterol over 40 mg/dl in this population.

[A clinico-anatomical correlation study of logorrhoea]. / Estudio de correlación clinicoanatómica de la logorrea.

INTRODUCTION: The degree of verbal production necessary to be considered logorrhoea has still not been defined, and no clear correlation has been established between the topography of the dysfunction and this symptom. AIMS: To provide quantitative data about normal verbal production and to identify the location within the brain of the alterations observed in neuroimage of patients with logorrhoea. SUBJECTS AND METHODS: The oral verbal production of 60 control subjects between 20 and 80 years of age was quantified by analysing five speeches. Ten patients who exceeded the 75th percentile in at least two of the five speeches underwent structural and functional neuroimaging tests. RESULTS. The data on verbal production of normal subjects are reported. Age, sex and habits (smoking, coffee, alcoholic drinks) did not exert an influence, but the degree of schooling was seen to have an effect. All the patients were diagnosed with frontotemporal degeneration, although in one case there were also coexisting vascular risk factors and subcortical vascular lesions, which reduce the degree of certainty of the diagnosis. Cortical atrophy is located in the right anterior temporal lobes (100% anteromedial, 100% anteroinferior, 70% anterolateral), left anterior temporal (90% anteromedial, 90% anteroinferior, 60% anterolateral), right prefrontal (30% basal, 50% dorsolateral, 20% medial) and left prefrontal (20% basal, 30% dorsolateral, 20% medial). CONCLUSIONS: Oral verbal production is influenced by level of education and, in a sample of patients with probable frontotemporal degeneration and logorrhoea, all the patients showed alterations in the anteroinferior and anteromedial regions of the right temporal lobe.

Estudio de correlación clinicoanatómica de la logorrea / A clinico anatomical correlation study of logorrhoeaa

Resumen. Introducción. Aún no se ha definido el grado de producción verbal necesario para identificar una logorrea y tampoco se ha establecido una correlación clara entre la topografía de la disfunción y el síntoma. Objetivos. Aportar datos cuantitativos de producción verbal normal e identificar la localización cerebral de las alteraciones en neuroimagen de pacientes con logorrea. Sujetos y métodos. Se ha cuantificado la producción verbal oral de 60 sujetos de control de entre 20 y 80 años, analizando cinco discursos. A 10 pacientes que superaron el percentil 75 en al menos dos de los cinco discursos se les realizaron pruebas de neuroimagen estructural y funcional. Resultados. Se presentan los datos de producción verbal de los sujetos normales. La edad, el sexo y hábitos (tabaco, café, bebidas alcohólicas) no mostraron influencia, pero sí el grado de formación académica. Todos los enfermos fueron diagnosticados de degeneración frontotemporal, aunque en un caso coexistían factores de riesgo vascular y lesiones vasculares subcorticales, que reducen seguridad al diagnóstico. La atrofia cortical se localiza en los lóbulos temporal anterior derecho (el 100% anteromedial, el 100% anteroinferior, el 70% anterolateral), temporal anterior izquierdo (el 90% anteromedial, el 90% anteroinferior, el 60% anterolateral), prefrontal derecho (el 30% basal, el 50% dorsolateral, el 20% medial) y prefrontal izquierdo (el 20% basal, el 30% dorsolateral, el 20% medial). Conclusiones. La producción verbal oral está influida por la formación académica y, en una muestra de pacientes con degeneración frontotemporal probable y logorrea, todos los enfermos mostraron alteración en las regiones anteroinferior y anteromedial del lóbulo temporal derecho (AU)

Summary. Introduction. The degree of verbal production necessary to be considered logorrhoea has still not been defined, and no clear correlation has been established between the topography of the dysfunction and this symptom. Aims. To provide quantitative data about normal verbal production and to identify the location within the brain of the alterations observed in neuroimage of patients with logorrhoea. Subjects and methods. The oral verbal production of 60 control subjects between 20 and 80 years of age was quantified by analysing five speeches. Ten patients who exceeded the 75th percentile in at least two of the five speeches underwent structural and functional neuroimaging tests. Results. The data on verbal production of normal subjects are reported. Age, sex and habits (smoking, coffee, alcoholic drinks) did not exert an influence, but the degree of schooling was seen to have an effect. All the patients were diagnosed with frontotemporal degeneration, although in one case there were also coexisting vascular risk factors and subcortical vascular lesions, which reduce the degree of certainty of the diagnosis. Cortical atrophy is located in the right anterior temporal lobes (100% anteromedial, 100% anteroinferior, 70% anterolateral), left anterior temporal (90% anteromedial, 90% anteroinferior, 60% anterolateral), right prefrontal (30% basal, 50% dorsolateral, 20% medial) and left prefrontal (20% basal, 30% dorsolateral, 20% medial). Conclusions. Oral verbal production is influenced by level of education and, in a sample of patients with probable frontotemporal degeneration and logorrhoea, all the patients showed alterations in the anteroinferior and anteromedial regions of the right temporal lobe (AU)

[The action of memantine on the cognitive disorders of patients with dementia: reflections following two years' experience in Spain]. / Acción de la memantina sobre la alteración cognitiva del paciente con demencia: reflexiones tras dos años de experiencia en España.

AIMS: To review the literature on the effectiveness of memantine in cognitive disorders, and to discuss data from our own personal experience. DEVELOPMENT: In moderately advanced or advanced stages of Alzheimer's disease (AD), use of memantine for cognitive disorders and functional independence is significantly effective, regardless of whether anticholinesterases are taken or not. Effectiveness lasts at least 1 year (open trial). The NNT (number needed to treat) of 7 means it has a value that is similar to that of anticholinesterases for the treatment of the early or moderate phases and the magnitude effect of 0.47 can be graded as intermediate. In incipient or moderate AD its effectiveness on the cognitive functions is lower. In early or moderate vascular dementia, memantine has favourable effects with regard to cognition, especially in dementia due to 'small-vessel' disease, although this is not reflected in functional independence, probably because it is also affected by other neurological and systemic factors. A retrospective analysis of 43 of our own cases (AD at GDS 6-7) showed a percentage of 'not worse' between successive visits (mean interval of 6 months) of 40-70%, the best result being obtained by those who take anticholinesterase. CONCLUSIONS: The effectiveness of memantine on cognitive impairment is significant in moderately advanced and advanced stages of AD, although we need to know physicians' impressions in order to determine the extent to which the first expectations from clinical trials are confirmed. This effect is less pronounced in the early and intermediate stages and in vascular dementia.

Acción de la memantina sobre la alteración cognitiva del paciente con demencia: reflexiones tras dos años de experiencia en España / The action of memantine on the cognitive disorders of patients with dementia: reflections following two years’ experience in spain

Objetivos. Revisar las publicaciones sobre eficacia de la memantina en la alteración cognitiva, y comentar datos procedentes de la experiencia personal. Desarrollo. En la enfermedad de Alzheimer (EA) moderadamente avanzada o avanzada, la eficacia de la memantina sobre las alteraciones cognitivas y la autonomía funcional es significativa, independientemente de que se tomen o no anticolinesterásicos. La efectividad persiste al menos un año (estudio abierto). El NNT (number needed to treat) de 7 le atribuye un valor equiparable al de los anticolinesterásicos para el tratamiento de la fase incipiente o moderada, y la magnitud del efecto de 0,47 es calificable de grado intermedio. En la EA incipiente o moderada, la efectividad sobre las funciones cognitivas es de menor grado. En la demencia vascular incipiente o moderada, la memantina resulta favorable para la cognición, especialmente en la demencia por enfermedad ‘de pequeño vaso’, aunque sin reflejo en la autonomía funcional, probablemente porque ésta se encuentra también perturbada por otros factores neurológicos y sistémicos. Un análisis retrospectivo de 43 casos propios (EA en GDS 6-7), muestra un porcentaje de ‘no empeoramiento’ entre consultas sucesivas (intervalo medio de 6 meses) del 40-70%, obteniendo mejor resultado los que toman un anticolinesterásico. Conclusiones. La eficacia de la memantina sobre la alteración cognitiva es significativa en la EA moderadamente avanzada y avanzada, aunque sería deseable conocer la impresión de los facultativos para comprobar en qué medida se confirman las primeras expectativas de la clínica experimental. El efecto es menor en la fase incipiente e intermedia y en la demencia vascular (AU)

Aims. To review the literature on the effectiveness of memantine in cognitive disorders, and to discuss data from our own personal experience. Development. In moderately advanced or advanced stages of Alzheimer’s disease (AD), use of memantine for cognitive disorders and functional independence is significantly effective, regardless of whether anticholinesterases are taken or not. Effectiveness lasts at least 1 year (open trial). The NNT (number needed to treat) of 7 means it has a value that is similar to that of anticholinesterases for the treatment of the early or moderate phases and the magnitude effect of 0.47 can be graded as intermediate. In incipient or moderate AD its effectiveness on the cognitive functions is lower. In early or moderate vascular dementia, memantine has favourable effects with regard to cognition, especially in dementia due to ‘small-vessel’ disease, although this is not reflected in functional independence, probably because it is also affected by other neurological and systemic factors. A retrospective analysis of 43 of our own cases (AD at GDS 6-7) showed a percentage of ‘not worse’ between successive visits (mean interval of 6 months) of 40-70%, the best result being obtained by those who take anticholinesterase. Conclusions. The effectiveness of memantine on cognitive impairment is significant in moderately advanced and advanced stages of AD, although we need to know physicians’ impressions in order to determine the extent to which the first expectations from clinical trials are confirmed. This effect is less pronounced in the early and intermediate stages and in vascular dementia (AU)

[Present and future of neurology in Spain]. / Presente y futuro de la neurología española.

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.

La investigación en la neurología del envejecimiento / Investigation in neurology of aging

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Demencia con cuerpos de Lewy: nuevas aportaciones a su conocimiento clínico / Dementia with lewy bodies: some contributions to the clinical knowledge

Introduction. Dementia with Lewy bodies is the second commonest type of dementia. The latest criteria for its diagnosis have recently been established (1996). Patients and methods. We report the clinical findings in 25 patients with probable dementia with Lewy bodies. Results. No sex predominance was seen, onset was after the age of 65 years in 60% of the cases and there was a past history of dementia in 48%. Onset was with cognitive disturbances in 32%, Parkinsonism in 32% and both in 32%. When there was an interval between Parkinsonism and dementia, this was of 3-19 months. The dementia included attention disorder, impaired recall nd praxis alterations. Disorders of executive function, behaviour or language, were seen in two thirds of the patients and acalculia in over half. Around 50% showed signs of subcortical involvement different from Parkinsonism. Parkinsonism was basically hypokinetic (96%), with tremor in two thirds of the cases, at rest (29%) postural (12%) or combined (59%), and symmetrical in 41%. Rigidity was only seen in 52% and was slight in most cases. In 16% there was weakness of vertical gaze. In 40% urine or double incontinence occurred, mainly when the dementia was at an intermediate or advanced state. Conclusions. Dementia with Lewy bodies is a dementia with fronto-temporo-parietal alterations, frequently associated with hypokinetic Parkinsonism (which always shows a lag period with respect to dementia of less than 24 months), hallucinations and a fluctuating course. Other findings supporting this diagnosis were seen in two out of every three patients (AU)

Introducción. La demencia con cuerpos de Lewy ocupa el segundo lugar entre las demencias por su fecuencia. Los últimos criterios para su diagnóstico se han establecido recientemente (1996). Pacientes y métodos. Presentamos las manifestaciones clínicas de 25 pacientes con demencia con cuerpos de Lewy probable. Resultados. No se observa predominio en el sexo, la instauración ha sido posterior a los 65 años en el 60% de los casos y hay antecedentes de demencia en el 48%. Comenzaron con alteración cognitiva (32%), con parkinsonismo (32%) y con ambos (32%). Cuando hubo intervalo parkinsonismo-demencia fue de 3-19 meses. En la demencia destacan el trastorno atencional, de la evocación mnésica y de la praxia. Las alteraciones de funciones ejecutivas, de la conducta o del lenguaje se objetivaron en dos de cada tres pacientes y hubo acalculia en más de la mitad. En torno al 50% mostraron signos de afectación subcortical diferentes al parkinsonismo. El parkinsonismo fue fundamentalmente hipocinético (96%), con temblor en dos tercios de los casos, de reposo (29%), postural (12%) o combinado (59%), y simétrico en el 41%. Sólo se observó rigidez en el 52%, y en la mayoría fue ligera. En un 16% hubo debilidad de la mirada vertical. Un 40% refirieron incontinencia de esfínteres, que mayoritariamente apareció cuando la demencia se hallaba en estadio intermedio o avanzado. Conclusiones. La demencia con cuerpos de Lewy es una demencia con alteraciones fronto-témporo-parietales, con asociación muy frecuente de parkinsonismo hipocinético (cuyo intervalo con la demencia es siempre inferior a 24 meses), alucinaciones y fluctuaciones. Las otras manifestaciones que apoyan el diagnóstico aparecen en dos de cada tres pacientes (AU)