Loss of Dopamine Transporter Binding and Clinical Symptoms in Dementia With Lewy Bodies.

BACKGROUND: Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies. The aim of this study was to explore the association between loss of striatal dopamine transporter binding and symptoms in dementia with Lewy bodies. METHODS: Thirty-five patients with dementia with Lewy bodies underwent single-photon emission computerized tomography brain imaging with N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane ([(123) I]FP-CIT). Associations between striatal binding ratios and motor (UPDRS), psychiatric (Neuropsychiatric Inventory; [NPI]), and cognitive (Mini-Mental State Examination [MMSE] and neuropsychological tests) symptoms were assessed by linear regression analysis. RESULTS: The explorative analysis showed that the motor UPDRS was negatively associated with putamen dopamine transporter binding, whereas no association with striatal dopamine transporter binding was found for total NPI, hallucinations, apathy, depression, anxiety, and MMSE scores. However, in post-hoc analysis, executive impairment was positively associated with dopamine transporter loss after adjustment of age and gender. CONCLUSIONS: Dopamine deficiency in patients with dementia with Lewy bodies was associated with severity of motor symptoms, but did not correlate significantly with ratings of neurobehavioral disturbances or overall cognition.

(123I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study.

OBJECTIVES: Little is known regarding the 'false-negative' or 'false-positive' striatal dopamine transporter binding on SPECT for the diagnosis of dementia with Lewy bodies (DLB). We explored the clinical course in patients fulfilling the criteria for clinical DLB with a normal ((123)I)FP-CIT SPECT (ie, SPECT scan negative, clinical features positive (S-CF+)) and patients not fulfilling DLB criteria with an abnormal scan (S+CF-). DESIGN: Longitudinal case study over 2-5 years. SETTING: Consecutive referrals of patients with mild dementia to dementia clinics in western Norway. PARTICIPANTS: 50 patients (27 men and 23 women; mean age at baseline of 74 (range 52-88)) with ((123)I)FP-CIT SPECT images underwent cluster analysis: 20/50 patients allocated to a 'DLB' and 8 to a 'non-DLB' cluster were included. OUTCOME MEASURES: Scores on standardised clinical rating scales for hallucinations, parkinsonism, fluctuations, rapid eye movement (REM) sleep behaviour disorder and visually rated ((123)I)FP-CIT SPECT. RESULTS: During the follow-up period, in the S+CF- group (n=7), frequency and severity of DLB symptoms tended to increase, particularly parkinsonism (7/7) and cognitive fluctuations (7/7), while severity of visual hallucinations and REM sleep behaviour disorder remained stable. The S-CF+ (n=3) fulfilled the operationalised criteria for probable DLB both at baseline and at the end of the follow-up. CONCLUSIONS: The findings suggest that systematic visual analyses of ((123)I)FP-CIT SPECT can detect people with DLB prior to the development of the full clinical syndrome. In addition, the study indicates that some patients fulfilling clinical criteria for probable DLB have a normal scan, and further studies are required to characterise these patients better.

Cell-cycle and apoptosis regulators (p16INK4A, p21CIP1, beta-catenin, survivin, and hTERT) and morphometry-defined MPECs predict metachronous cancer development in colorectal adenoma patients.

BACKGROUND AND AIMS: Although adenomas may be precursors to colorectal cancers (CRC), knowledge concerning the development of metachronous CRC is scarce. We assessed whether differential expression of cell-cycle and apoptosis-regulating proteins and a monotonous population of elongated cells (MPECs) in colorectal adenomas could predict metachronous CRC. METHODS: Application of immunohistochemistry on tissue microarrays in consecutive, population-based colorectal adenomas. Influence of classic features (e.g., intraepithelial neoplasia grade, histological type, size) was examined. RESULTS: Of 171 patients with colorectal adenoma 86% (n=147) were eligible for study; 10 (7%) developed metachronous CRC. Median time to cancer was 69 months (range, 25-256). Median follow-up was equal for the non-cancer and cancer groups. Elevated expression of cell-cycle regulators p16(INK4A), p21(CIP1), and cytoplasmic/nuclear beta-catenin correlated with increased CRC risk (all P<0.0001), as did elevated expression of the anti-apoptosis protein survivin (P<0.0001) and human telomerase reverse transcriptase (hTERT; P<0.001). Survivin, hTERT, and nuclear beta-catenin were the most predictive molecular markers (hazard ratios [HRs]: 6.3, 9.4, and 5.8, respectively). In a combined multivariate model, MPECs had the best overall prognostic ability (HR 28.2, 95% CI: 3.6-223.0), together with survivin, and hTERT. Within adenomas containing MPECs, several molecular markers further defined high-risk patients. CONCLUSIONS: Among several markers predictive for metachronous CRC development in colorectal adenomas, MPECs, survivin and hTERT may, when validated, provide information superior to conventional histology, with relevance for the clinical management of patients with colorectal adenoma.

A monotonous population of elongated cells (MPECs) in colorectal adenoma indicates a high risk of metachronous cancer.

Accurate predictors for metachronous colorectal cancer (CRC) development after polypectomy are lacking. We evaluated the prognostic value of classical clinicopathologic features and a monotonous population of elongated cells (MPECs) in colorectal adenomas from 171 consecutively selected population-based patients with long-term follow-up. Quantitative image analysis, and univariate and multivariate regression analysis were applied. Ten of 171 adenomas (5.8%) developed metachronous CRC (defined as >24 mo interval and >5 cm from the index adenoma to the cancer). Median follow-up of adenomas with metachronous CRC was 68.4 and without cancer 149.7 months (range: 25 to 192 and 25 to 256, respectively). The most prognostic classical features were the localization of the marker adenoma as proximal (ie, in the cecum through transverse colon) versus distal from the transverse colon [P=0.0003, hazard ratio (HR)=8] and the number of polyps found during colonoscopy (2, P=0.002, HR=6). Quantitative features of the MPECs included the longest nuclear axis and variance of the number of nuclei with 2 neighbors (higher and lower in cancer cases, respectively). Of the 171 adenomas, 50 (29%) had MPECs, of which 9 (18%) patients developed metachronous CRC at follow-up, contrasting 1/121 (0.8%) without MPECs (P=0.0003, HR=23). MPECs occurred in both low-grade and high-grade dysplasia, and in tubular and (tubulo) villous adenomas. MPECs had the strongest predictive value for metachronous CRC development. Adenomas proximally located had additional value but only if they were MPEC positive (which only occurred in 5 adenomas, 3 of which (60%) developed cancer). Having more than 2 polyps also had additional prognostic value but only in MPEC-negative adenomas [10 cases; 1 (10%) developed cancer]. Dysplasia grade and histologic growth pattern had no additional value. Thus, colorectal adenomas with subsequent metachronous cancer development can be identified more accurately with MPECs than with classical prognostic factors.