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

Prince of Wales Medical Research Institute and University of New South Wales, Sydney, NSW, Australia.
Brain (Impact Factor: 10.23). 11/2002; 125(Pt 11):2431-45.
Source: PubMed

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.

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    ABSTRACT: ABSTRACT Background: Dementia with Lewy body (DLB) is considered to be the second most common form of neurodegenerative disorders after Alzheimer's disease (AD), affecting as many as 100,000 people in the UK and up to 1.3 million in the USA. However, nearly half of patients with DLB remain undiagnosed thus depriving many of them from an early and adequate treatment of their distressing symptoms. Accurate and early diagnosis of DLB is important for both patients and their caregivers, since the neuropsychiatric symptoms require specific management. Methods: In the current study, we review the most recent developments in the field of molecular nuclear imaging to diagnose DLB. Results: The review addresses, the neurotransmitter based (dopaminergic, cholinergic, and glutamatergic) nuclear imaging techniques, role of the autonomic dysfunction and its visualization in DLB with myocardial sympathetic imaging and vesicular catecholamine uptake, as well as the use of amyloid polypeptides and glial markers as molecular imaging probes in the clinical diagnosis of DLB. Conclusions: Most of the above nuclear imaging methods are restricted to highly specialized clinical centers, and thus not applicable to a large number of patients requiring dementia (e.g. DLB) diagnosis in routine clinical setting. Validating them against more readily accessible peripheral biomarkers, e.g. CSF and blood biomarkers linked to the DLB process, may facilitate their use in wider clinical settings.
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