Calcium channel blockers, survival and ischaemic stroke in patients with dementia: a Swedish registry study.

BACKGROUND: The effect of calcium channel blockers (CCB) on mortality and ischaemic stroke risk in dementia patients is understudied. OBJECTIVES: To calculate the risk of death and ischaemic stroke in dementia patients treated with CCBs, considering individual agents and dose response. METHODS: Longitudinal cohort study with 18 906 hypertensive dementia patients from the Swedish Dementia Registry (SveDem), 2008-2014. Other Swedish national registries contributed information on comorbidities, dispensed medication and outcomes. Individual CCB agents and cumulative defined daily doses (cDDD) were considered. RESULTS: In patients with hypertension and dementia, nifedipine was associated with increased mortality risk (aHR 1.32; CI 1.01-1.73; P < 0.05) compared to non-CCB users. Patients diagnosed with Alzheimer's dementia (AD) or dementia with Lewy bodies/Parkinson's disease dementia (DLB-PDD) taking amlodipine had lower mortality risk (aHR, 0.89; CI, 0.80-0.98; P < 0.05 and aHR 0.58; CI, 0.38-0.86; P < 0.01, respectively), than those taking other CCBs. Amlodipine was associated with lower stroke risk in patients with Alzheimer's dementia compared to other CCBs (aHR 0.63; CI, 0.44-0.89; P < 0.05). Sensitivity analyses with propensity score-matched cohorts repeated the results for nifedipine (aHR 1.35; 95% CI, 1.02-1.78; P < 0.05) and amlodipine in AD (aHR, 0.87; CI, 0.78-0.97; P < 0.05) and DLB-PDD (aHR, 0.56, 95%CI, 0.37-0.85; P < 0.05). CONCLUSION: Amlodipine was associated with reduced mortality risk in dementia patients diagnosed with AD and DLB-PDD. AD patients using amlodipine had a lower risk of ischaemic stroke compared to other CCB users.

Connecting the brain cholesterol and renin-angiotensin systems: potential role of statins and RAS-modifying medications in dementia.

Millions of people worldwide receive agents targeting the renin-angiotensin system (RAS) to treat hypertension or statins to lower cholesterol. The RAS and cholesterol metabolic pathways in the brain are autonomous from their systemic counterparts and are interrelated through the cholesterol metabolite 27-hydroxycholesterol (27-OHC). These systems contribute to memory and dementia pathogenesis through interference in the amyloid-beta cascade, vascular mechanisms, glucose metabolism, apoptosis, neuroinflammation and oxidative stress. Previous studies examining the relationship between these treatments and cognition and dementia risk have produced inconsistent results. Defining the blood-brain barrier penetration of these medications has been challenging, and the mechanisms of action on cognition are not clearly established. Potential biases are apparent in epidemiological and clinical studies, such as reverse epidemiology, indication bias, problems defining medication exposure, uncertain and changing doses, and inappropriate grouping of outcomes and medications. This review summarizes current knowledge of the brain cholesterol and RAS metabolism and the mechanisms by which these pathways affect neurodegeneration. The putative mechanisms of action of statins and medications inhibiting the RAS will be examined, together with prior clinical and animal studies on their effects on cognition. We review prior epidemiological studies, analysing their strengths and biases, and identify areas for future research. Understanding the pathophysiology of the brain cholesterol system and RAS and their links to neurodegeneration has enormous potential. In future, well-designed epidemiological studies could identify potential treatments for Alzheimer's disease (AD) amongst medications that are already in use for other indications.

Management of acute ischaemic stroke in patients with dementia.

An estimated 10% of stroke patients have an underlying dementia. As a consequence, health professionals often face the challenge of managing patients with dementia presenting with an acute stroke. Patients with dementia are less likely to receive thrombolysis (0.56-10% vs. 1-16% thrombolysis rates in the general population), be admitted to a stroke unit or receive some types of care. Anticoagulation for secondary stroke prevention is sometimes withheld, despite dementia not being listed as an exclusion criterion in current guidelines. Studies in this population are scarce, and results have been contradictory. Three observational studies have examined intravenous thrombolysis for treatment of acute ischaemic stroke in patients with dementia. In the two largest matched case-control studies, there were no significant differences between patients with and without dementia in the risks of intracerebral haemorrhage or mortality. The risk of intracerebral haemorrhage ranged between 14% and 19% for patients with dementia. Studies of other interventions for stroke are lacking for this population. Patients with dementia are less likely to be discharged home compared with controls (19% vs. 41%) and more likely to be disabled (64% vs. 59%) or die during hospitalization (22% vs. 11%). The aim of this review was to summarize current knowledge about the management of ischaemic stroke in patients with pre-existing dementia, including organizational aspects of stroke care, intravenous thrombolysis, access to stroke unit care and use of supportive treatment. Evidence to support anticoagulation for secondary prevention of stroke in patients with atrial fibrillation and antiplatelet therapy in nonembolic stroke will be discussed, as well as rehabilitation and how these factors influence patient outcomes. Finally, ethical issues, knowledge gaps and pathways for future research will be considered.

Quejas cognitivas subjetivas: hacia una identificación precoz de la enfermedad de Alzheimer / Subjective cognitive impairment: Towards early identification of Alzheimer disease

Introducción: La neurodegeneración en enfermedad de Alzheimer (EA) empieza décadas antes que la demencia y algunos pacientes con deterioro cognitivo leve presentan una importante carga lesional. La ausencia de información sobre la fisiopatología temprana de la enfermedad dificulta la búsqueda de estrategias terapéuticas. La queja cognitiva subjetiva (QCS) agrupa a sujetos con quejas mnésicas sin déficits significativos en test neuropsicológicos. Es un síndrome heterogéneo sobre el que no existe consenso, pero algunos de estos pacientes podrían representar el estadio más precoz de EA. Método: Realizamos una revisión bibliográfica para resumir el estado del conocimiento actual sobre quejas cognitivas subjetivas. Resultados: Aunque a nivel individual no presenten enfermedad objetivable, a nivel de grupo los pacientes con QCS rinden peor en test neuropsicológicos que la población general y tienen mayor incidencia de declive cognitivo futuro. La depresión y la comorbilidad psiquiátrica desempeñan un papel pero no son la única causa de quejas cognitivas. Estudios con resonancia magnética muestran un patrón de atrofia hipocampal similar al del deterioro cognitivo leve amnésico y en resonancia funcional hay aumento de activación en tareas cognitivas que podrían representar una compensación ante pérdida de función. Los pacientes con QCS presentan un patrón tipo EA de marcadores betaamiloide (A 42) y tau con mayor frecuencia que la población general. Conclusiones: Las quejas mnésicas son un síntoma relevante y podrían predecir EA. La heterogeneidad de los pacientes y de los ensayos clínicos ha dificultado la definición del síndrome. En el futuro, una definición estandarizada y estudios longitudinales con un seguimiento suficiente, y centrados en variables cuantificables, podrían clarificar aspectos tempranos de la EA

Introduction: Neurodegeneration in Alzheimer disease (AD) begins decades before dementia and patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. Lack of information about the early pathophysiology in AD complicates the search for therapeutic strategies. Subjective cognitive impairment is the description given to subjects who have memory-related complaints without pathological results on neuropsychological tests. There is no consensus regarding this heterogeneous syndrome, but at least some of these patients may represent the earliest stage in AD. Method: We reviewed available literature in order to summarise current knowledge on subjective cognitive impairment. Results: Although they may not present detectable signs of disease, SCI patients as a group score lower on neuropsychological tests than the general population does, and they also have a higher incidence of future cognitive decline. Depression and psychiatric co-morbidity play a role but cannot account for all cognitive complaints. Magnetic resonance imaging studies in these patients reveal a pattern of hippocampal atrophy similar to that of amnestic mild cognitive impairment and functional MRI shows increased activation during cognitive tasks which might indicate compensation for loss of function. Prevalence of an AD-like pattern of beta-amyloid (A 42) and tau proteins in cerebrospinal fluid is higher in SCI patients than in the general population. Conclusions: Memory complaints are relevant symptoms and may predict AD. Interpatient variability and methodological differences between clinical studies make it difficult to assign a definition to this syndrome. In the future, having a standard definition and longitudinal studies with sufficient follow-up times and an emphasis on quantifiable variables may clarify aspects of early AD

Antidepressants and mortality risk in a dementia cohort: data from SveDem, the Swedish Dementia Registry.

BACKGROUND: The association between mortality risk and use of antidepressants in people with dementia is unknown. OBJECTIVE: To describe the use of antidepressants in people with different dementia diagnoses and to explore mortality risk associated with use of antidepressants 3 years before a dementia diagnosis. METHODS: Study population included 20 050 memory clinic patients from the Swedish Dementia Registry (SveDem) diagnosed with incident dementia. Data on antidepressants dispensed at the time of dementia diagnosis and during 3-year period before dementia diagnosis were obtained from the Swedish Prescribed Drug Register. Cox regression models were used. RESULTS: During a median follow-up of 2 years from dementia diagnosis, 25.8% of dementia patients died. A quarter (25.0%) of patients were on antidepressants at the time of dementia diagnosis, while 21.6% used antidepressants at some point during a 3-year period before a dementia diagnosis. Use of antidepressant treatment for 3 consecutive years before a dementia diagnosis was associated with a lower mortality risk for all dementia disorders and in Alzheimer's disease. CONCLUSION: Antidepressant treatment is common among patients with dementia. Use of antidepressants during prodromal stages may reduce mortality in dementia and specifically in Alzheimer's disease.

Auriculotemporal Neuralgia: Eight New Cases Report.

BACKGROUND: Auriculotemporal neuralgia (ATN) is an infrequent syndrome consisting in strictly unilateral pain in the temporal region associated with nerve tenderness, which can be successfully treated with anesthetic blockade. We analysed clinical characteristics and treatment response in a series of eight patients. METHODS: Series of consecutive patients diagnosed with ATN at Headache Clinics of two university hospitals in Spain. Data on demographic and pain characteristics, as well as response to treatment are presented. RESULTS: Eight patients (seven women). Mean age at onset was 52.8 ± 14.3 years. Pain was strictly unilateral (left-sided in five cases, right-sided in three), and triggered by pressing the preauricular area. Four patients presented background pain, mostly dull in quality, with an intensity of 5.75 ± 1.2 on the verbal analogical scale (VAS). In six, burning exacerbations occurred, ranging from 2 seconds to 30 minutes, with intensity 7.3 ± 1.5 on VAS. Complete relief was achieved with gabapentin in three cases, anaesthetic blockade in three and spontaneously in two. CONCLUSION: ATN is uncommon in headache units. Gabapentin is a good alternative therapeutic option to anesthetic blockade.

Subjective cognitive impairment: Towards early identification of Alzheimer disease. / Quejas cognitivas subjetivas: hacia una identificación precoz de la enfermedad de Alzheimer.

INTRODUCTION: Neurodegeneration in Alzheimer disease (AD) begins decades before dementia and patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. Lack of information about the early pathophysiology in AD complicates the search for therapeutic strategies.Subjective cognitive impairment is the description given to subjects who have memory-related complaints without pathological results on neuropsychological tests. There is no consensus regarding this heterogeneous syndrome, but at least some of these patients may represent the earliest stage in AD. METHOD: We reviewed available literature in order to summarise current knowledge on subjective cognitive impairment. RESULTS: Although they may not present detectable signs of disease, SCI patients as a group score lower on neuropsychological tests than the general population does, and they also have a higher incidence of future cognitive decline. Depression and psychiatric co-morbidity play a role but cannot account for all cognitive complaints. Magnetic resonance imaging studies in these patients reveal a pattern of hippocampal atrophy similar to that of amnestic mild cognitive impairment and functional MRI shows increased activation during cognitive tasks which might indicate compensation for loss of function. Prevalence of an AD-like pattern of beta-amyloid (Aß42) and tau proteins in cerebrospinal fluid is higher in SCI patients than in the general population. CONCLUSIONS: Memory complaints are relevant symptoms and may predict AD. Interpatient variability and methodological differences between clinical studies make it difficult to assign a definition to this syndrome. In the future, having a standard definition and longitudinal studies with sufficient follow-up times and an emphasis on quantifiable variables may clarify aspects of early AD.

Body mass index in dementia.

This review comprehensively examines the current knowledge on the relationship between body mass index (BMI) and dementia. The association between BMI and cognition is complex: in younger adults, higher BMIs are associated with impaired cognition. Overweight and obesity in middle age are linked to increased future dementia risk in old age. However, when examined in old age, higher BMIs are associated with better cognition and decreased mortality. Little is known about the optimal BMI for well-being and survival in populations already suffering from dementia. Lifetime trends in weight, rather than single measures, might predict prognosis better and help untangle these apparent contradictions. Thus, the need arises to properly monitor BMI trends in affected dementia patients. Registries can include BMI, improving the management of dementia patients throughout the whole course of the disease. The role of central obesity and systemic inflammation on brain pathology and cognitive decline are discussed in this review. Understanding the life-course changes in BMI and their influence on dementia risk, cognitive prognosis and mortality after diagnosis may provide new insights into the underlying pathophysiology of dementia and shape possible intervention and treatment strategies.

Las alucinaciones y percepciones aberrantes son prevalentes entre la población joven sana / Hallucinations and aberrant perceptions are prevalent among the young healthy adult population

Introducción: Las alucinaciones son frecuentes en la práctica clínica y presentan una incidencia poblacional de hasta el 38,7%. El objetivo del estudio es determinar la prevalencia de percepciones aberrantes entre jóvenes sanos de nuestro entorno. Sujetos y métodos: Estudio observacional entre estudiantes de 3.° a 6.° curso de medicina de la Universidad Complutense de Madrid, que realizan prácticas en el Hospital Clínico San Carlos. Tras una encuesta de cribado, se realizó una entrevista individual a aquellos sujetos que presentaban percepciones aberrantes. Recogimos datos epidemiológicos mediante anamnesis semiestructurada administrada por una residente de tercer año de Neurología. Resultados: N=134 (edad media 22,1 años, 77,6% mujeres); 74 respondedores contestaron afirmativamente a alguna de las preguntas de cribado y 54 completaron la entrevista. El 22,2% presentó fenómenos visuales y el 64,8% auditivos. La mayoría describieron fenómenos asociados al sueño y percepciones auditivas, como oír el teléfono o el timbre de la puerta sin que hubieran sonado (38,8%). Todos presentaron crítica de los episodios y ninguno refirió síntomas psicóticos. Dos casos se asociaron a tóxicos. Conclusiones: Las percepciones aberrantes son muy frecuentes entre la población general. Clásicamente, se asocian los fenómenos auditivos a patología psicótica y otros estudios dan una incidencia poblacional baja (0,6%). Sin embargo, en nuestra serie las percepciones auditivas de corta duración y con crítica inmediata eran frecuentes y no se asociaban a patología(AU)

Introduction: Hallucinations are frequent in clinical practice, with an incidence of up to 38.7% in the general population. We aim to determine the prevalence of hallucinations among healthy young adults in our environment. Subjects and methods: We designed an observational study, using as subjects 3rd to 6th year medical students at the Universidad Complutense de Madrid who complete clinical rotations in the Hospital Clínico San Carlos. After a screening questionnaire, an individual interview was conducted via telephone or e-mail to those students who reported hallucinations. We obtained clinical and epidemiological data through a semi-structured clinical interview performed by a third year neurology resident. Results: N=134 (average age was 22.1 years; 77.6% were women). 74 respondents answered affirmatively to one or more screening questions, and 54 completed the follow-up interview. 22.2% described visual phenomena and 64.8%, auditory. The majority reported sleep-related experiences and auditory perceptions related to hyper vigilance, such as hearing the telephone or the doorbell ring when in fact it had not (38.8%). All subjects had good insight into their experiences and none had psychotic symptoms. Two cases were associated with substance abuse. Conclusions: Hallucinations are frequent among the general population. Traditionally, auditory phenomena have been associated with psychotic pathology, and other studies show a low population incidence (0.6%). However, in our sample, short auditory perceptions with immediate analysis were frequent and not pathological(AU)

Hallucinations and aberrant perceptions are prevalent among the young healthy adult population.

INTRODUCTION: Hallucinations are frequent in clinical practice, with an incidence of up to 38.7% in the general population. We aim to determine the prevalence of hallucinations among healthy young adults in our environment. SUBJECTS AND METHODS: We designed an observational study, using as subjects 3rd to 6th year medical students at the Universidad Complutense de Madrid who complete clinical rotations in the Hospital Clínico San Carlos. After a screening questionnaire, an individual interview was conducted via telephone or e-mail to those students who reported hallucinations. We obtained clinical and epidemiological data through a semi-structured clinical interview performed by a third year neurology resident. RESULTS: N=134 (average age was 22.1 years; 77.6% were women). 74 respondents answered affirmatively to one or more screening questions, and 54 completed the follow-up interview. 22.2% described visual phenomena and 64.8%, auditory. The majority reported sleep-related experiences and auditory perceptions related to hyper vigilance, such as hearing the telephone or the doorbell ring when in fact it had not (38.8%). All subjects had good insight into their experiences and none had psychotic symptoms. Two cases were associated with substance abuse. CONCLUSIONS: Hallucinations are frequent among the general population. Traditionally, auditory phenomena have been associated with psychotic pathology, and other studies show a low population incidence (0.6%). However, in our sample, short auditory perceptions with immediate analysis were frequent and not pathological.

Síndrome de encefalopatía posterior reversible recurrente con respuesta a nimodipino / Recurrent reversible posterior encephalopathy syndrome with a response to nimodipine

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Migraine-triggered hemifacial spasm: three new cases.

BACKGROUND: The occurrence of hemifacial spasm (HFS) during an episode of migraine has been seldom reported. Here we describe three new cases presenting with HFS in association with migraine attacks. CASE RESULTS: Three patients (one woman and two men, aged 31-36 years) developed HFS in close temporal relationship with migraine headaches. All of them started having the muscle spasms after pain onset. Two of them had electromyographic evidence of facial nerve damage, and continued having HFS once the pain abated. CONCLUSIONS: Migraine attacks may be associated with HFS. The appearance of HFS could be related to migraine activity. A mechanism of central hyperexcitability in connection with nociceptive inputs on the trigeminal nucleus caudalis and/or a dilation of vessels compressing the facial nerve at the root exit zone could lead to the development of HFS in predisposed patients. 'Migraine-triggered hemifacial spasm' could possibly be regarded as a complication of migraine.