Clinical correlates of selective pathology in the amygdala of patients with Parkinson’s disease

Abstract

The amygdala exhibits significant pathological changes in Parkinson's disease, including atrophy and Lewy body (LB) formation. Amygdala pathology has been suggested to contribute to some clinical features of Parkinson's disease, including deficits of olfaction and facial expression. The degree of neuronal loss in amygdala subnuclei and the relationship with LB formation in non-demented Parkinson's disease cases have not been examined previously. Using stereological methods, the volume of neurones and the number of neurones in amygdala subdivisions were estimated in 18 prospectively studied, non-demented patients with Parkinson's disease and 16 age- and sex-matched controls. Careful exclusion (all cortical disease) and inclusion (non-demented, levodopa-responsive, idiopathic Parkinson's disease or controls) criteria were applied. Seven Parkinson's disease cases experienced well-formed visual hallucinations many years after disease onset, while nine Parkinson's disease cases and three controls were treated for depression. Anatomically, the amygdala was subdivided into the lateral nucleus, the basal (basolateral and basomedial) nuclei and the corticomedial (central, medial and cortical nuclei) complex. LB and Lewy neurites were identified by immunohistochemistry for alpha-synuclein and ubiquitin and were assessed semiquantitatively. LB were found throughout the amygdala in Parkinson's disease, being present in approximately 4% of neurones. Total amygdala volume was reduced by 20% in Parkinson's disease (P = 0.02) and LB concentrated in the cortical and basolateral nuclei. Lewy neurites were present in most cases but did not correlate with any structural or functional variable. Amygdala volume loss was largely due to a 30% reduction in volume (P = 0.01) and the total estimated number of neurones (P = 0.007) in the corticomedial complex. The degree of neurone loss and the proportion of LB-containing neurones in the cortical nucleus within this complex were constant across Parkinson's disease cases and neither variable was related to disease duration (R(2 )< 0.03; P > 0.5). The cortical nucleus has major olfactory connections and its degeneration is likely to contribute to the early selective anosmia common in Parkinson's disease. There was a small reduction in neuronal density in the basolateral nucleus in all Parkinson's disease cases, but no consistent volume or cell loss within this region. However, the proportion of LB-containing neurones in the basolateral nucleus was nearly doubled in cases that exhibited visual hallucinations, suggesting that neuronal dysfunction in this nucleus contributes to this late clinical feature. Detailed quantitation of the other amygdala subdivisions failed to reveal any other substantial anomalies or any associations with depression. Thus, the impact of Parkinson's disease on the amygdala is highly selective and correlates with both early and late clinical features.

The neuropathological basis for depression in Parkinson's disease

“…These findings are discrepant from previous research that observed amygdala pathology in PD patients irrespective of affective state [30]. One possibility, though doubtful in such an elderly population, is that our sample of PD subjects were in the earlier-intermediate Braak neuropathological stages (i.e., stages 3-4) of PD, and limbic-cortical pathology occur at the more intermediate-later neuropathological stages (i.e., 4-6) of PD [31].…”

Facial Emotion Recognition and Discrimination Deficit in Idiopatic Parkinson Patients

“…Neuroimaging studies showed that facial emotion processing is regulated by a circuitry involving inferior frontal area projecting onto prefrontal and temporo-parietal cortices (24,26). Especially right hemisphere amygdala and basal ganglia play a key role in emotional processing (27). Since the aminergic neurotransmitters affected by the IPD pathology operate on this frontal-subcortical circuits and basal ganglia, abnormalities in mood states, cognition and motor functions may present themselves (28).…”

REM Sleep Behavior Disorder in Parkinson's Disease: A Questionnaire-Based Survey

“…Harding and Halliday showed that both groups had LB in limbic structures, in particular in the basolateral nucleus of the amygdala. 36 The main difference between the two groups was the absence of neocortical LB in the patients without dementia. 36,37 Based on these findings, they suggested that visual hallucinations and cognitive impairment in PD are likely to have different underlying pathology.…”