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Original Articles • Dement. neuropsychol. 2 (3) • Jul-Sep 2008 • https://doi.org/10.1590/S1980-57642009DN20300004   copy

Alzheimer disease neuropathology:understanding autonomic dysfunction

A neuropatologia da doença de Alzheimer: entendendo a disfunção autônoma

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Alzheimer's disease is a widely studied disorder with research focusing on cognitive and functional impairments, behavioral and psychological symptoms, and on abnormal motor manifestations. Despite the importance of autonomic dysfunctions they have received less attention in systematic studies. The underlying neurodegenerative process of AD, mainly affecting cortical areas, has been studied for more than one century. However, autonomic-related structures have not been studied neuropathologically with the same intensity. The autonomic nervous system governs normal visceral functions, and its activity is expressed in relation to homeostatic needs of the organism's current physical and mental activities. The disease process leads to autonomic dysfunction or dysautonomy possibly linked to increased rates of morbidity and mortality.

Objective:

The aim of this review was to analyze the cortical, subcortical, and more caudal autonomic-related regions, and the specific neurodegenerative process in Alzheimer's disease that affects these structures.

Methods:

A search for papers addressing autonomic related-structures affected by Alzheimer's degeneration, and under normal condition was performed through MedLine, PsycInfo and Lilacs, on the bibliographical references of papers of interest, together with a manual search for classic studies in older journals and books, spanning over a century of publications.

Results:

The main central autonomic-related structures are described, including cortical areas, subcortical structures (amygdala, thalamus, hypothalamus, brainstem, cerebellum) and spinal cord. They constitute autonomic neural networks that underpin vital functions. These same structures, affected by specific Alzheimer's disease neurodegeneration, were also described in detail. The autonomic-related structures present variable neurodegenerative changes that develop progressively according to the degenerative stages described by Braak and Braak.

Conclusion:

The neural networks constituted by the central autonomic-related structures, when damaged by progressive neurodegeneration, represent the neuropathological substrate of autonomic dysfunction. The presence of this dysfunction and its possible relationship with higher rates of morbidity, and perhaps of mortality, in affected subjects must be kept in mind when managing Alzheimer's patients.

Key words:
Alzheimer; neurodegeneration; autonomic; autonomic dysfunction; dysautonomy.

Resumo

A doença da Alzheimer é uma doença amplamente estudada com foco nos comprometimentos cognitivo e funcional, sintomas de comportamento e psicológicos e manifestações motoras anormais. As disfunções autônomas, apesar de sua importância, foram menos consideradas por estudos sistemáticos. O processo neurodegenerativo subjacente dessa doença, principalmente nas áreas corticais, vem sendo estudado há mais de um século. Entretanto, estruturas autônomas não foram estudadas do ponto de vista neuropatológico com o mesmo interesse. O sistema nervoso autônomo encontra-se relacionado a funções viscerais normais e sua atividade é expressa em relação a necessidades homeostáticas das atividades correntes físicas e mentais do organismo. O processo da doença leva a disfunção autônoma ou disautonomia, possivelmente relacionada com taxas maiores de morbidade e mortalidade.

Objetivo:

O foco dessa revisão é analisar as estruturas autônomas corticais, subcorticais e mais caudais, assim como o processo neurodegenerativo específico da doença de Alzheimer que acomete essas estruturas.

Métodos:

Foi realizada busca de artigos sobre estruturas autônomas atingidas pela degeneração de Alzheimer e em condições de normalidade, através do MedLine, PsycInfo e Lilacs, assim como nas referências bibliográficas dos artigos de interesse encontrados, busca manual de estudos clássico em periódicos e livros mais antigos, abrangendo mais de um século de publicações.

Resultados:

As principais estruturas autônomas centrais são analisadas do ponto de vista funcional, incluindo áreas corticais, estruturas subcorticais (amígdala, tálamo, hipotálamo, tronco cerebral) e medula. Estas constituem as redes neurais autônomas subjacentes às funções vitais. As mesmas estruturas, atingidas pela neurodegeneração específica da doença de Alzheimer foram também descritas de modo detalhado. As estruturas autônomas apresentam alterações neurodegenerativas de grau variável que se desenvolvem de modo progressivo de acordo com os estágios degenerativos descritos por Braak e Braak.

Conclusão:

As redes neurais constituídas pelas estruturas autônomas centrais, quando lesadas pela neurodegeneração progressive, representam o substrato neuropatológico da disfunção autônoma. A presença dessa disfunção e sua possível relação com taxas mais elevadas de morbidade e talvez de mortalidade entre os indivíduos comprometidos deve ser considerada quando se trata de pacientes com doença de Alzheimer.

Palavras-chave:
Alzheimer; neurodegeneração; autônomo; disfunção autônoma disautonomia

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Publication Dates

  • Publication in this collection
    Jul-Sep 2008

History

  • Received
    14 July 2008
  • Accepted
    22 Aug 2008
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