CLBs detected by alpha-synuclein antibodies in patients with PD are a more sensitive and specific correlate of dementia than the presence of Alzheimer's pathology, which was present in a minority of the cases in this series.

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Autosomal dominant myopathy, Paget disease of bone, and dementia constitute a unique disorder (MIM 605382). Here we describe the clinical, biochemical, radiological, and pathological characteristics of 49 affected (23 male, 26 female) individuals from four unrelated United States families. Among these affected individuals 90% have myopathy, 43% have Paget disease of bone, and 37% have premature frontotemporal dementia. EMG shows myopathic changes and muscle biopsy reveals nonspecific myopathic changes or blue-rimmed vacuoles. After candidate loci were excluded, a genome-wide screen in the large Illinois family showed linkage to chromosome 9 (maximum LOD score 3.64 with marker D9S301). Linkage analysis with a high density of chromosome 9 markers generated a maximum two-point LOD score of 9.29 for D9S1791, with a maximum multipoint LOD score of 12.24 between D9S304 and D9S1788. Subsequent evaluation of three additional families demonstrating similar clinical characteristics confirmed this locus, refined the critical region, and further delineated clinical features of this unique disorder. Hence, autosomal dominant inclusion body myopathy (HIBM), Paget disease of bone (PDB), and frontotemporal dementia (FTD) localizes to a 1.08-6.46 cM critical interval on 9p13.3-12 in the region of autosomal recessive IBM2.

Temporal lobectomy is an effective therapy for medically refractory temporal lobe epilepsy (TLE), but may be complicated by amnestic syndromes. Therefore, pre-surgical evaluation to assess the risk/benefit ratio for surgery is required. Intracarotid amobarbital testing (IAT) is currently the most widely used method for assessing pre-surgical memory lateralization, but is relatively invasive. Over the past decade functional MRI (fMRI) has been shown to correlate with IAT for language lateralization, and also for memory lateralization in a small number of patients. This study was carried out to compare fMRI during memory encoding with IAT testing for memory lateralization, and to assess the predictive value of fMRI during memory encoding for post-surgical memory outcome. Thirty-five patients with refractory TLE undergoing pre-surgical evaluation for temporal lobectomy and 30 normal subjects performed a complex visual scene-encoding task during fMRI scanning at 1.5 T using a 10-min protocol. Encoding performance was evaluated with subsequent recognition testing. Twenty-three patients also completed the same task again outside the scanner, an average of 6.9 months following surgery. A region of interest (ROI) analysis was used to quantify activation within hippocampal and a larger mesial temporal lobe ROI consisting of hippocampus, parahippocampus and fusiform gyrus (HPF) as defined by a published template. Normal subjects showed almost symmetrical activation within these ROI. TLE patients showed greater asymmetry. Asymmetry ratios (ARs) from the HPF ROI correlated significantly with memory lateralization by intracarotid amobarbital testing. HPF ARs also correlated significantly with memory outcome, as determined by a change in scene recognition between pre-surgical and post-surgical trials. When absolute activation within the HPF ROI was considered, a significant inverse correlation between activation ipsilateral to temporal lobectomy and memory outcome was observed, with no significant correlation in the contralateral HPF ROI. Although further technical improvements and prospective clinical validation are required, these results suggest that mesial temporal memory activation detected by fMRI during complex visual scene encoding correlates with post-surgical memory outcome and supports the notion that this approach will ultimately contribute to patient management.