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

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. Thirty-five patients with dementia with Lewy bodies underwent single-photon emission computerized tomography brain imaging with N-ω-fluoropropyl-2β-carbomethoxy-3β-(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. 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. 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 cognitio

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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

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

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-). Longitudinal case study over 2-5 years. Consecutive referrals of patients with mild dementia to dementia clinics in western Norway. 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. 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. 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. 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 bette

(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, α-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 cellcycle regulators p16INK4A, p21CIP1, and cytoplasmic/nuclear α-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 α-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