Neurobiology of apathy in Alzheimer's disease

Abstract

-Apathy is considered the most frequent neuropsychiatric disturbance in dementia and its outcome is generally deleterious. Apathy can be related to a dysfunction of the anatomical-system that supports the generation of voluntary actions, namely the prefrontal cortex and/or the prefrontal-subcortical circuits. In Alzheimer's disease, pathological and neuroimaging data indicate that apathy is likely due to a dysfunction of the medial prefrontal cortex. Accordingly, in this review article, we propose a pathophysiological model to explain apathetic behavior in Alzheimer's disease, combining data from neuroimaging, neuropathology and experimental research on the role of orbito-frontal cortex, anterior cingulate cortex, basal ganglia and dopamine in decision-making neurobiology.Key words: apathy, Alzheimer's disease, decision-making, orbito-frontal cortex, anterior cingulate cortex, basal ganglia, dopamine. Neurobiologia da apatia na doença de alzheimerResumo -Apatia é considerada a alteração neuropsiquiátrica mais freqüente nas demências e suas conseqüências são habitualmente deletérias. Apatia pode ser relacionada à disfunção do sistema anatômico responsável pela geração de ações voluntárias, conhecido com córtex pré-frontal e/ou circuitos pré-frontais-subcorticais. Na doença de Alzheimer, evidências neuropatológicas e de neuroimagem funcional indicam que a apatia é provavelmente decorrente da disfunção do córtex pré-frontal medial. Assim, neste artigo de revisão, apresentamos uma proposta de um modelo fisiopatológico para explicar o comportamento apático na doença de Alzheimer, combinando dados de neuropatologia, neuroimagem e experimentação animal sobre o papel do córtex órbito-frontal, cíngulo anterior, núcleos da base e dopamina na neurobiologia da tomada de decisão.PAlAvrAs-chAve: apatia, doença de Alzheimer, tomada de decisão, córtex órbito-frontal, córtex cingulado anterior, núcleos da base, dopamina.

Neuropsychiatry of Parkinson's disease

“…Apathy is a syndrome with motivational, emotional, cognitive and behavioral characteristics. They include a reduced interest and participation in daily activities, a lack of initiative and difficulty in sustaining an activity to completion, lack of concern or indifference, and a flattening of affect 99 . Between 16% and 42% of PD patients report apathy 100,101 .…”

“…Indeed, apathetic PD patients have worse cognitive performance, especially of executive functions, than non-apathetic patients 103 . The association between cognition and apathy, along with the potential benefit of anticholinesterasic drugs on both cognition and apathy, suggests that cholinergic mechanisms take part in the pathophysiology of apathy 99,100 . On the other side, a mitochondrial malfunction or the increased metabolic rate of PD, due to muscular rigidity or neuroinflammatory mechanisms, may be the causes of fatigue 104 .…”

Alzheimer's disease and implicit memory

“…Priming is influenced by frontal cortex, which may reflect its attentional demands [32][33][34] and procedural memory is influenced by the striatum, sensorimotor cortex and cerebellum 30,35,36 , which may reproduce its motor skills. explicit memory impairment is one of the earliest AD symptoms, and its loss characterizes all the stages of AD 37 . Although some types of implicit memory are also lost in AD, certainly, other ones are preserved into late stages of disease 5 .…”

Perfil neuropsiquiátrico na doença de Alzheimer e na demência mista

“…Apatia e depressão aparecem ainda entre os principais sintomas em pacientes com DA em um estudo brasileiro de base populacional 20 . A relevância da apatia na DA já é bem conhecida 13,21,22 , sendo o principal sintoma observado em pacientes demenciados, de acordo com o que foi observado nos casos de DM do presente estudo, em que apatia foi o sintoma neuropsiquiá-trico mais relatado (71,7% dos pacientes).…”