Hallucinations And Dementia In Parkinson’s Disease: Clinically Related But Structurally Distinct (P5.257)

Objective: To examine the neuroanatomical substrates of hallucinations and dementia using structural brain magnetic resonance imaging (MRI) in Parkinson’s disease (PD). Background: Hallucinations and dementia, two frequent, disabling complications of PD, are inter-twined clinically. Hallucinations are a risk factor for dementia, and demented PD patients are more likely to develop hallucinations. Despite their shared clinical occurrences, it is unknown whether they have similar neuroanatomical substrates, and prior structural MRI studies have not examined these PD complications independently. Methods: Twenty-five PD subjects with current and chronic hallucinations were matched for cognitive status (demented/non-demented) and age (+/- 3 years) to 25 PD subjects without hallucinations. Subjects underwent brain MRI scans using a 1.5 T GE Signa scanner with T1-weighted MPRAGE sequences. Whole brain voxel-based morphometry (VBM) analyses were conducted using SPM8. Regions of gray matter volume differences were examined with a 2x2 factorial design (hallucinator vs. non-hallucinator groups, controlling for dementia, and demented vs. non-demented groups, controlling for hallucinations). Statistical significance was set at p<0.01 uncorrected. Results: When controlling for dementia, the hallucinators exhibited significant reductions in gray matter volume in brain regions including the cuneus, fusiform, lingual, middle occipital, precentral, and cingulate gyri and inferior parietal lobules, compared to the non-hallucinators. Conversely, when controlling for hallucinations, the demented group had significant reductions in gray matter volumes in the parahippocampal gyri, hippocampus, amygdala, uncus and insula; inferior frontal, medial frontal, and middle frontal gyri; and superior temporal gyri, compared to the non-demented group. Conclusion: Our structural MRI findings demonstrate a dissociation between the brain regions associated with hallucinations (predominantly visuoperceptive occipital-temporal-parietal areas) and dementia (predominantly frontal, temporal, and limbic regions), which has not been previously reported. Localized abnormalities in the visuoperceptive system may explain the visual nature of PD hallucinations. Moreover, these underlying neurobiological differences may help guide the development of specific treatments targeting hallucinations and dementia in PD. Study support by: K23NS060949 (JGG), Parkinson9s Disease Foundation. Disclosure: Dr. Goldman has received personal compensation for activities with American Academy of Neurology, Movement Disorder Society, Johns Hopkins Dystonia and Spasticity Practicum, and Teva Neuroscience. Dr. Goldman has received research support from NIH/NINDS and the Parkinson9s Disease Foundation. Dr. Stebbins has received personal compensation for activities with Adamas Pharmaceuticals, Ceregene Inc., CHDI Management, Ingenix Pharmaceuticals, and Neurocrine Biosciences as a consultant. Dr. Merkitch has nothing to disclose. Dr. Dinh has nothing to disclose. Dr. Bernard has received research support from the Parkinson9s Disease Foundation. Dr. DeToledo-Morrell has nothing to disclose. Dr. Goetz has received personal compensation for activities with AOP Orphan, Addex Pharma, Advanced Studies of Medicine, Boston Scientific Corp., CHDI Foundation, Health Advances, ICON Clinical Research, Ingenix, and the National Institutes of Health. Dr. Goetz has received personal compensation in an editorial capacity for Oxford University Press, Elsevier Publishers, Wolters Kluwer Health-Lippincott, Wilkins and Williams, Movement Disorder, American Academy of Neurology, and the Unviersity of Pennsylvania. Dr. Goetz has received research support from the National Institutes of Health, the Michael J Fox Foundation, and The Parkinson9s Disease Foundation.