Mixed dementia: A review of the evidence / Demência mista: revisão das evidências

ABSTRACT. Mixed dementia is the coexistence of Alzheimer's disease and cerebrovascular disease (CVD) in the same demented patient. Currently, its diagnosis and treatment remains a challenge for practitioners. To provide an overview of the epidemiology, pathogenesis, natural history, diagnosis, and therapy of Mixed Vascular-Alzheimer Dementia (MVAD). The literature was reviewed for articles published between 1990-2016 by using the keywords linked to MVAD. Neuropathological studies indicate that MVAD is a very common pathological finding in the elderly with a prevalence about of 22%. The distinction between Alzheimer's dementia and vascular dementia (VD) is complex because their clinical presentation can overlap. There are international criteria for the MVAD diagnosis. The pharmacologic therapy shows modest clinical benefits that are similar among all drugs used in patients with Alzheimer's dementia and VD. The non-pharmacologic therapy includes the rigorous management of cardiovascular risk factors (especially hypertension) and the promotion of a healthy diet. The diagnosis and treatment of MVAD cannot be improved without further studies. Currently available medications provide only modest clinical benefits once a patient has developed MVAD. In subjects at risk, the antihypertensive therapy and healthy diet should be recommend for preventing or slowing the progression of MVAD.

RESUMO. Demência mista é denominação usual para a coexistência da doença de Alzheimer e doença cerebrovascular (DCV) no mesmo paciente demente. Atualmente, seu diagnóstico e tratamento continuam sendo um desafio. Fornecer uma visão geral da epidemiologia, patogênese, história natural, diagnóstico e terapia da Demência Mista Alzheimer-Vascular (DMAV). Foi realizada revisão da literatura buscando por artigos publicados entre 1990 e 2016 usando palavras-chave relacionadas ao DMAV. Estudos neuropatológicos indicam que DMAV é um achado patológico muito comum em idosos, com uma prevalência de cerca de 22%. A distinção entre demência de Alzheimer e demência vascular (DV) é complexa porque suas apresentações clínicas podem se sobrepor. Existem critérios internacionais para o diagnóstico DMAV. A terapia farmacológica mostra benefícios clínicos modestos que são semelhantes para todos os medicamentos utilizados em pacientes com demência de Alzheimer e DV. A terapia não-farmacológica inclui o manejo rigoroso dos fatores de risco cardiovascular (especialmente a hipertensão) e a promoção de uma dieta saudável. O diagnóstico e o tratamento do DMAV não podem ser melhorados sem outros estudos. Os medicamentos atualmente disponíveis fornecem apenas benefícios clínicos modestos, depois que DMAV instalou-se. Em indivíduos em risco, a terapia anti-hipertensiva e uma dieta saudável devem ser recomendadas para prevenir ou retardar a progressão da DMAV.

Comprometimento cognitivo vascular: leucoaraiose, hipocampos e espectroscopia de prótons ? Estudo preliminar / Vascular cognitive impairment: leucoaraiosis, hippocampi, and proton spectroscopy – Preliminary study

Introdução: O continuum do comprometimento cognitivo vascular (CCV) compreende segmento não demência (CCV-ND), segmento demência (CCV-D ou DV), sendo o subtipo mais frequente o CCV subcortical, e inclui, ainda, formas mistas (CCV + DA). Ressonância magnética (RM) do cérebro é o método mais apropriado para avaliação das lesões vasculares, dimensão dos hipocampos e do espectro de prótons (1HMRS). Objetivo: Comparar os valores de metabólitos dos hipocampos (HC) e da região do cíngulo posterior (CP) em grupos de casos de CCV subcortical. Métodos: Casos (n = 55) foram selecionados a partir do banco de dados sobre CCV. Imagens obtidas por equipamento Signa Horizon LX-GE de 1,5T, com protocolo-padrão para aquisição estrutural (incluindo FLAIR, T2 e aquisição para 1H-MRS). Metabólitos estudados (relações) incluíram: Naa/Cr, Co/Cr e mI/Cr. Os casos foram definidos radiologicamente (leucoaraiose grau 3 pela escala de Fazekas modificada) e subdivididos de acordo com a escala de Leon (0-3) em dois em grupos hipocampais (grHC): grHC [0+1] e grHC [2+3]. Análise estatística pelo ANOVA e Tukey. Resultados: A relação Naa/Cr nos HC mostrou diferença significativa entre o grHC [0+1] e o grHC [2+3], o que representa diminuição de integridade (perda) neuronal no segundo, enquanto os CP desses grupos mantiveram os valores estáveis. Houve diferença significativa entre o grHC [2+3] em relação aos CP de ambos os grupos, enquanto o grHC [0+1] ficou compatível com os valores dos CP. Comparação dos valores obtidos em estudos anteriores em CCL e DA mostrou o Naa/Cr com valor intermediário entre os do CCL e da DA nos HC e equivalência de valores nos CP. Conclusão: A 1HMRS possibilita analisar o grau de perda neuronal, além de alterações de membrana e neuroglial dessas regiões. Assim, podem ser obtidas informações para melhor compreender o continuum CCV subcortical (que pode incluir CCV + DA), visando determinar a contribuição dessas duas patologias, caso haja, ao comprometimento cognitivo...

Introduction: Vascular cognitive impairment (VCI) continuum comprisesno-dementia segment (VCI-ND), dementia segment (VCI-D or VaD), with subcortical VCI as the most frequent subtype, and additionally mixed forms (VCI + AD). Magnetic resonance imaging (MRI) of the brain is the most proper method for vascular lesions, hippocampal size, and proton spectrum (1HMRS) assessment. Objective: Comparison of the values of metabolites at the hippocampi (HC) and posterior cingulate (PC) region of groups of cases of subcortical VCI. Methods: Cases (n = 55) were selected from a database on VCI. Images were obtained with Signa Horizon LX-GE de 1.5T equipment and a standard protocol for structural and 1H-MRS acquisitions. Studied metabolites (reasons) were: Naa/Cr, Coh/Cr e mI/Cr. The cases were radiologically defined (grade 3 leucoaraiosis on modified Fazekas scale), and according de Leon?s scale (0-3) subdivided in two hippocampal groups (grHC): grHC[0+1] and grHC[2+3]. Statistical analysis with ANOVA and Tukey. Results: The reason Naa/Cr at the HC showed a significant difference between the grHC[0+1] and grHC[2+3], that represents a reduction of neuronal integrity (loss) in the latter, while at PC these groups maintained stable values. There was a significant difference between grHC [2+3] in relation to PC of both groups, while grHC [0+1] remained compatible with PC values. The comparison of the values obtained from previous studies on MCI and AD showed Naa/Cr with intermediate values between MCI and AD at the HC, and equivalence at the PC. Conclusion: 1HMRS allows for the analysis of the degree of neuronal loss, besides membrane and neuroglial changes of these regions. Thus, information may be obtained for a better understanding of the subcortical VCI continuum (that may include VCI + AD), aiming to determine the contribution of these two pathologies, if present, to the cognitive impairment...

Perfil cognoscitivo de adultos mayores de 60 años con y sin deterioro cognoscitivo / Cognitive profile of adults over 60 years with and without cognitive impairment

Introducción: En el envejecimiento, las funciones cognoscitivas se caracterizan por un decremento y variabilidad en sus procesos, discernir si se trata de un envejecimiento normal o un deterioro patológico es clínicamente difícil; los límites no son precisos, además, intervienen variables como la edad, escolaridad y las diferencias poblacionales. Con el objetivo de caracterizar el perfil neuropsicológico de adultos mayores de 60 años con y sin deterioro cognoscitivo se estudió una muestra de 536 adultos mayores de 60 años con queja subjetiva o de familiares en los proceso de memoria, los cuales, fueron pacientes del Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” de la Ciudad de México, entre los años 2006 a 2010. Por consenso interdisciplinario de especialistas con énfasis en la evaluación neuropsicológica, se dividió la muestra en: Envejecimiento Normal (EN), Deterioro cognitivo Leve (DCL), Enfermedad de Alzheimer (EA), Demencia Vascular (DV) y Demencia Mixta (DM). Con puntajes Z se calculó estadística descriptiva y un ANOVA de medidas repetidas. Resultados: Se encontraron diferencias estadísticas en el rendimiento de la evaluación neuropsicológica entre los grupos. El 29 por ciento de la muestra fue EN que no presenta alteraciones objetivas de funciones cognoscitivas. El más alto porcentaje fue el 46 por ciento del grupo DCL, que mostraron alteraciones en memoria y atención. La EA con el 12 por ciento, presenta alteraciones severas en memoria, funciones ejecutivas y lenguaje. El 7 por ciento del grupo DV la atención, la visuoconstructivo, el cálculo y la coordinación motora fueron las funciones afectadas. Por su parte, en el perfil de DM que representa el 6 por ciento, mostro mayor severidad en las alteraciones cognoscitivas afectadas.

Introduction: During aging cognitive function processes may decrease and fluctuate. This makes the task of distinguishing between normal aging and pathological deterioration clinically difficult. Variables such as age, academic level and social demographics combine to impede an objective analysis. The goal of the study was to characterize the neuropsychological profile of Mexican senior citizens who expressed a subjective complaint regarding memory. Method: A sample of 536 people over the age of 60 was studied. Each had reported memory issues between2006 and 2010 at the Salvador Zubiran National Institute of Medical Science and Nutrition. For interdisciplinary consensus the sample was divided into: Normal Aging (NA), Slight Cognitive Deterioration (SCD), Alzheimer Disease (AL), Vascular Dementia (VA) and Mixed Dementia (MD). Z points were used to calculate ANOVA with repeated measurements. Results: The population yielded statistical differences stemming from neuropsychological evaluations. 29 percent of the sample were classified NA with no current objective alterations in cognitive functions. The largest group, 46 percent, were classified as SCD, manifesting some alterations in memory and attention. AL was found in 12 percent with severe alterations in memory, executive functions and language. A similar cognitive profile was shared with the 6 percent of the group with MD, with only difference in the severity of cognitive alterations. Those with a VA profile manifested affected functions for attention, visual construction, calculation and motor coordination.

Effects of Galantamine Treatment on Attention, Activities of Daily Living, and Neuropsychiatric Symptoms between the Patients with Pure Alzheimer's Disease and Mixed Dementia

OBJECTIVES: The purpose of this study was to compare the efficacy of galantamine treatment, especially attention ability between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 24-week trial. METHODS: A total of 40 patients were recruited for this 24-week study. The effect of galantamine on attention was measured using Seoul Computerized NeuroCognitive Function Test (SCNT) and frontal functions test of Seoul Neuropsychological Screening Battery (SNSB). Patients'activities of daily living using the Seoul-Activities of Daily Living (S-ADL) and the Seoul-Instrumental Activities of Daily Living (S-IADL) ; behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline and 24-week. RESULTS: 17 pure AD patients and 23 MD patients were analyzed in this study. Attention as measured by SCNT was not significantly different from baseline after 24 weeks of treatment in both groups. There was no significant difference between two groups in mean change from baseline in the SCNT, S-ADL, S-IADL and K-NPI scores at 24-week. CONCLUSION: Galantamine showed a therapeutic effect on cognition, activities of daily living, neuropsychiatric symptoms in pure AD and MD. Furthermore, Galantamine may specifically help to maintain attention and it may have positive effects on other cognitive and functional abilities.

Comparative Assessment of Clinical Efficacy after 12-Month Clinical Trial of Donepezil between the Patients with Pure Alzheimer's Disease and Mixed Dementia

OBJECTIVES: The purpose of this study was to compare the efficacy of donepezil treatment between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 12-month trial. METHODS: A total of 139 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using the Seoul-Instrumental Activities of Daily Living (S-IADL) and Seoul-Activities of Daily Living (S-ADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 84 pure AD patients and 34 MD patients were available for intent-to-treat (ITT) last observation carried forward (LOCF) analysis. There was no significant difference between two groups in mean change from baseline in the total ADAS-cog-k, S-ADL, S-IADL and K-NPI scores at 52-week. Based on the operational criteria, 60.7% of pure AD patients and 58.8% of MD patients were responders to donepezil. CONCLUSION: MD patients had similar levels of efficacy with pure AD patients and donepezil was well tolerated in both groups. These results suggest that donepezil is an effective and well-tolerated treatment for MD patients as well as for pure AD patients.

Comparative Assessment of Clinical Efficacy after 12-Month Clinical Trial of Donepezil between the Patients with Pure Alzheimer's Disease and Mixed Dementia

OBJECTIVES: The purpose of this study was to compare the efficacy of donepezil treatment between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 12-month trial. METHODS: A total of 139 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using the Seoul-Instrumental Activities of Daily Living (S-IADL) and Seoul-Activities of Daily Living (S-ADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 84 pure AD patients and 34 MD patients were available for intent-to-treat (ITT) last observation carried forward (LOCF) analysis. There was no significant difference between two groups in mean change from baseline in the total ADAS-cog-k, S-ADL, S-IADL and K-NPI scores at 52-week. Based on the operational criteria, 60.7% of pure AD patients and 58.8% of MD patients were responders to donepezil. CONCLUSION: MD patients had similar levels of efficacy with pure AD patients and donepezil was well tolerated in both groups. These results suggest that donepezil is an effective and well-tolerated treatment for MD patients as well as for pure AD patients.

Perfil neuropsiquiátrico na doença de Alzheimer e na demência mista / Neuropsychiatric profile in Alzheimer's disease and in mixed dementia

Alguns estudos sugerem que infartos cerebrais possam agravar a demência em pacientes com doença de Alzheimer (DA) e que sintomas neuropsiquiátricos sejam comuns tanto na DA quanto na demência vascular (DV). Doença cerebrovascular concomitante à DA incorre na chamada demência mista (DM). OBJETIVOS: Comparar a freqüência e o perfil dos sintomas neuropsiquiátricos em uma amostra de pacientes com DA e DM. MÉTODOS: Análise retrospectiva dos prontuários de 70 pacientes com diagnóstico de DA provável e 14 com DM. Informações sobre sintomatologia neuropsiquiátrica foram obtidas por meio dos relatos de familiares e cuidadores. RESULTADOS: A média etária foi de 74,5 anos na DA e 75,1 na DM. O sintoma mais comum na DA foi agitação (61,4 por cento), enquanto na DM foi apatia (71,7 por cento). Na DM, nove (64,3 por cento) pacientes apresentavam > 5 sintomas, enquanto na DA, 40 (57,1 por cento) apresentavam < 4. Quarenta e cinco (64,3 por cento) pacientes com DA tinham > 4 anos de doença; na DM, 10 (71,4 por cento) tinham < 3 anos. Pacientes com DM mostraram menor duração de sintomas (p < 0,05), sugerindo que tenham procurado atendimento médico mais precocemente. CONCLUSÕES: Os pacientes com DM exibiram maior gravidade de sintomas neuropsiquiátricos, fato que pode ter sido responsável pela busca mais precoce de assistência especializada.

Some studies suggest that concomitant cerebral infarction may worsen the severity of dementia in patients with Alzheimer disease (AD) and that neuropsychiatric symptoms are common either in patients with AD and vascular dementia. AD lesions together with cerebrovascular disease is commonly called mixed dementia (MD). METHODS: A retrospective analysis was carried out in medical charts of 70 patients with probable AD and 14 with MD. Information on neuropsychiatric symptoms was based on caregivers' and families' reports. RESULTS: Mean age was 74.5 years in AD and 75.1 in MD. The most common symptom in AD was agitation (61.4 percent), while in MD apathy was more common (71.7 percent). In MD, 9 (64.3 percent) patients had 5 or more symptoms, while in AD, 40 (57.1 percent) had 4 or less. Forty-five (64.3 percent) patients with AD had more than 4 years of disease; in MD, 10 (71.4 percent) had less than 3 years. Patients with MD showed shorter duration of symptoms (p<0.05), suggesting that these patients search earlier for medical treatment. CONCLUSIONS: Patients with MD exhibited a greater severity of neuropsychiatric symptoms, which may have been responsible for the earlier need of specialized assistance.

A novel rat model of senile dementia / 中华物理医学与康复杂志

Objective To establish a novel model of senile dementia in rats. Methods Fifty-two Wistar male rats were divided into 5 groups, group A was treated with a permanent bilateral occlusion of both carotid arteries (2-VO) first and then intraperitoneal injection of D-galactose (60 mg?kg -1 ?d -1 ,ip,42 d), group B with intraperitoneal injection of D-galactose (60 mg?kg -1 ?d -1 ,ip,42 d) first and then permanent bilateral occlusion of both carotid arteries, group C with 2-VO, group D with intraperitoneal injection of D-galactose, and group E (normal control) without the above treatment. All the rats were tested by using Morris water maze for their performance in learning and memory. Results Wistar rats treated with both 2-VO and D-galactose presented a significant diffe-rence from those simply treated by 2-VO and the normal rats. Conclusion The rat model of senile dementia induced by 2-VO and D-galactose simulated some characteristics of human senile dementia, and might be used in basic experiment study of senile dementia, such as vascular dementia, Alzheimer′s disease and mixed dementia.

Differential Diagnosis of Vascular Dementia and Alzheimer's Disease

Differential diagnosis of Alzheimer's disease (AD) and vascular dementia(VaD) has an important bearing on the diagnosis and management of patients with dementia. This article provides a guideline for the differential diagnosis through 1) history taking, 2) neurological examination, 3) neuropsychological tests, and 4) neuroimaging studies. VaD consists of etiologically and clinically heterogeneous subtypes that include multi-infarct dementia (MID), single strategic infarct dementia, and subcortical vascular dementia. Patients with MID and single infarct dementia con be easily differentiated from patients with AD. However, clinical manifestations of subcortical vascular dementia can mimic those of AD, which may lead primary physicians to misdiagnose subcortical vascular dementia as AD. The issue of differential diagnosis is further complicated by the fact that many patients may have AD with concomitant VaD (mixed dementia).