Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and ... more Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and human cortex. Four of the ergots are selective for rat 5-HT2 receptors--mesulergine, methysergide, nicergoline and metergoline, whereas pergolide, d-lysergic acid, ergonovine, ergotamine, d-lysergic acid diethylamide, lisuride and dihydroergotamine display selectivity for human 5-HT2 receptors. Rat-selective compounds contain a methyl substitution on the indole nitrogen, whereas human-selective compounds contain a hydrogen. This structural feature may allow the two groups of ergots to differentiate between the two species of receptors.
Pascual S anchez Juan, Pia Ghosh, Jayne Hagen, Benno Gesierich, Maya Henry, Maria-Luisa Gorno-Tem... more Pascual S anchez Juan, Pia Ghosh, Jayne Hagen, Benno Gesierich, Maya Henry, Maria-Luisa Gorno-Tempini, Bruce Miller, William Jagust, Gil Rabinovici, University Hospital Marqu es de Valdecilla, Santander, Spain; UCSF Memory and Aging Center, San Francisco, California, United States; UCSF Memory and Aging Center, San Francisco, California, United States; University of California, Berkeley, Berkeley, California, United States. Contact e-mail: psanchez@ humv.es
Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and ... more Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and human cortex. Four of the ergots are selective for rat 5-HT2 receptors--mesulergine, methysergide, nicergoline and metergoline, whereas pergolide, d-lysergic acid, ergonovine, ergotamine, d-lysergic acid diethylamide, lisuride and dihydroergotamine display selectivity for human 5-HT2 receptors. Rat-selective compounds contain a methyl substitution on the indole nitrogen, whereas human-selective compounds contain a hydrogen. This structural feature may allow the two groups of ergots to differentiate between the two species of receptors.
Objective: To evaluate the interrater reliability of the new International Behavioural Variant FT... more Objective: To evaluate the interrater reliability of the new International Behavioural Variant FTD Criteria Consortium (FTDC) criteria for behavioral variant frontotemporal dementia (bvFTD). Methods: Twenty standardized clinical case modules were developed for patients with a range of neurodegenerative diagnoses, including bvFTD, primary progressive aphasia (nonfluent, semantic, and logopenic variant), Alzheimer disease, and Lewy body dementia. Eighteen blinded raters reviewed the modules and 1) rated the presence or absence of core diagnostic features for the FTDC criteria, and 2) provided an overall diagnostic rating. Interrater reliability was determined by k statistics for multiple raters with categorical ratings. Results: The mean k value for diagnostic agreement was 0.81 for possible bvFTD and 0.82 for probable bvFTD ("almost perfect agreement"). Interrater reliability for 4 of the 6 core features had "substantial" agreement (behavioral disinhibition, perseverative/compulsive, sympathy/empathy, hyperorality; k 5 0.61-0.80), whereas 2 had "moderate" agreement (apathy/inertia, neuropsychological; k 5 0.41-0.6). Clinician years of experience did not significantly influence rater accuracy. Conclusions: The FTDC criteria show promise for improving the diagnostic accuracy and reliability of clinicians and researchers. As disease-altering therapies are developed, accurate differential diagnosis between bvFTD and other neurodegenerative diseases will become increasingly important. Neurology â 2013;80:1973-1977 GLOSSARY bvFTD 5 behavioral variant frontotemporal dementia; DLB 5 dementia with Lewy bodies; FTDC 5 International Behavioural Variant FTD Criteria Consortium; lvPPA 5 logopenic variant primary progressive aphasia; nfPPA 5 nonfluent variant primary progressive aphasia; SE 5 standard error; svPPA 5 semantic variant primary progressive aphasia; UC
Objective: To evaluate the effect of amyloid imaging on clinical decision making. Methods: We con... more Objective: To evaluate the effect of amyloid imaging on clinical decision making. Methods: We conducted a retrospective analysis of 140 cognitively impaired patients (mean age 65.0 years, 46% primary b-amyloid (Ab) diagnosis, mean Mini-Mental State Examination 22.3) who underwent amyloid (Pittsburgh compound B [PiB]) PET as part of observational research studies and were evaluated clinically before and after the scan. One hundred thirty-four concurrently underwent fluorodeoxyglucose (FDG)-PET. We assessed for changes between the pre-and post-PET clinical diagnosis (from Ab to non-Ab diagnosis or vice versa) and Alzheimer disease treatment plan. The association between PiB/FDG results and changes in management was evaluated using x 2 and multivariate logistic regression. Postmortem diagnosis was available for 24 patients (17%). Results: Concordance between scan results and baseline diagnosis was high (PiB 84%, FDG 82%). The primary diagnosis changed after PET in 13/140 patients (9%) overall but in 5/13 (38%) patients considered pre-PET diagnostic dilemmas. When examined independently, discordant PiB and discordant FDG were both associated with diagnostic change (unadjusted p , 0.0001). However, when examined together in a multivariate logistic regression, only discordant PiB remained significant (adjusted p 5 0.00013). Changes in treatment were associated with discordant PiB in patients with non-Ab diagnoses (adjusted p 5 0.028), while FDG had no effect on therapy. Both PiB (96%) and FDG (91%) showed high agreement with autopsy diagnosis. Conclusions: PET had a moderate effect on clinical outcomes. Discordant PiB had a greater effect than discordant FDG, and influence on diagnosis was greater than on treatment. Prospective studies are needed to better characterize the clinical role of amyloid PET. Neurology ® 2014;82:230-238 GLOSSARY Ab 5 b-amyloid; AD 5 Alzheimer disease; AUC 5 appropriate use criteria; CBS 5 corticobasal syndrome; CDR 5 Clinical Dementia Rating; Che-I 5 cholinesterase inhibitor; CMS 5 Centers for Medicare & Medicaid Services; DLB 5 dementia with Lewy bodies; FDG 5 fluorodeoxyglucose; FTD 5 frontotemporal dementia; MCI 5 mild cognitive impairment; PiB 5 Pittsburgh compound B; UCSF
Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and ... more Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and human cortex. Four of the ergots are selective for rat 5-HT2 receptors--mesulergine, methysergide, nicergoline and metergoline, whereas pergolide, d-lysergic acid, ergonovine, ergotamine, d-lysergic acid diethylamide, lisuride and dihydroergotamine display selectivity for human 5-HT2 receptors. Rat-selective compounds contain a methyl substitution on the indole nitrogen, whereas human-selective compounds contain a hydrogen. This structural feature may allow the two groups of ergots to differentiate between the two species of receptors.
Pascual S anchez Juan, Pia Ghosh, Jayne Hagen, Benno Gesierich, Maya Henry, Maria-Luisa Gorno-Tem... more Pascual S anchez Juan, Pia Ghosh, Jayne Hagen, Benno Gesierich, Maya Henry, Maria-Luisa Gorno-Tempini, Bruce Miller, William Jagust, Gil Rabinovici, University Hospital Marqu es de Valdecilla, Santander, Spain; UCSF Memory and Aging Center, San Francisco, California, United States; UCSF Memory and Aging Center, San Francisco, California, United States; University of California, Berkeley, Berkeley, California, United States. Contact e-mail: psanchez@ humv.es
Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and ... more Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and human cortex. Four of the ergots are selective for rat 5-HT2 receptors--mesulergine, methysergide, nicergoline and metergoline, whereas pergolide, d-lysergic acid, ergonovine, ergotamine, d-lysergic acid diethylamide, lisuride and dihydroergotamine display selectivity for human 5-HT2 receptors. Rat-selective compounds contain a methyl substitution on the indole nitrogen, whereas human-selective compounds contain a hydrogen. This structural feature may allow the two groups of ergots to differentiate between the two species of receptors.
Objective: To evaluate the interrater reliability of the new International Behavioural Variant FT... more Objective: To evaluate the interrater reliability of the new International Behavioural Variant FTD Criteria Consortium (FTDC) criteria for behavioral variant frontotemporal dementia (bvFTD). Methods: Twenty standardized clinical case modules were developed for patients with a range of neurodegenerative diagnoses, including bvFTD, primary progressive aphasia (nonfluent, semantic, and logopenic variant), Alzheimer disease, and Lewy body dementia. Eighteen blinded raters reviewed the modules and 1) rated the presence or absence of core diagnostic features for the FTDC criteria, and 2) provided an overall diagnostic rating. Interrater reliability was determined by k statistics for multiple raters with categorical ratings. Results: The mean k value for diagnostic agreement was 0.81 for possible bvFTD and 0.82 for probable bvFTD ("almost perfect agreement"). Interrater reliability for 4 of the 6 core features had "substantial" agreement (behavioral disinhibition, perseverative/compulsive, sympathy/empathy, hyperorality; k 5 0.61-0.80), whereas 2 had "moderate" agreement (apathy/inertia, neuropsychological; k 5 0.41-0.6). Clinician years of experience did not significantly influence rater accuracy. Conclusions: The FTDC criteria show promise for improving the diagnostic accuracy and reliability of clinicians and researchers. As disease-altering therapies are developed, accurate differential diagnosis between bvFTD and other neurodegenerative diseases will become increasingly important. Neurology â 2013;80:1973-1977 GLOSSARY bvFTD 5 behavioral variant frontotemporal dementia; DLB 5 dementia with Lewy bodies; FTDC 5 International Behavioural Variant FTD Criteria Consortium; lvPPA 5 logopenic variant primary progressive aphasia; nfPPA 5 nonfluent variant primary progressive aphasia; SE 5 standard error; svPPA 5 semantic variant primary progressive aphasia; UC
Objective: To evaluate the effect of amyloid imaging on clinical decision making. Methods: We con... more Objective: To evaluate the effect of amyloid imaging on clinical decision making. Methods: We conducted a retrospective analysis of 140 cognitively impaired patients (mean age 65.0 years, 46% primary b-amyloid (Ab) diagnosis, mean Mini-Mental State Examination 22.3) who underwent amyloid (Pittsburgh compound B [PiB]) PET as part of observational research studies and were evaluated clinically before and after the scan. One hundred thirty-four concurrently underwent fluorodeoxyglucose (FDG)-PET. We assessed for changes between the pre-and post-PET clinical diagnosis (from Ab to non-Ab diagnosis or vice versa) and Alzheimer disease treatment plan. The association between PiB/FDG results and changes in management was evaluated using x 2 and multivariate logistic regression. Postmortem diagnosis was available for 24 patients (17%). Results: Concordance between scan results and baseline diagnosis was high (PiB 84%, FDG 82%). The primary diagnosis changed after PET in 13/140 patients (9%) overall but in 5/13 (38%) patients considered pre-PET diagnostic dilemmas. When examined independently, discordant PiB and discordant FDG were both associated with diagnostic change (unadjusted p , 0.0001). However, when examined together in a multivariate logistic regression, only discordant PiB remained significant (adjusted p 5 0.00013). Changes in treatment were associated with discordant PiB in patients with non-Ab diagnoses (adjusted p 5 0.028), while FDG had no effect on therapy. Both PiB (96%) and FDG (91%) showed high agreement with autopsy diagnosis. Conclusions: PET had a moderate effect on clinical outcomes. Discordant PiB had a greater effect than discordant FDG, and influence on diagnosis was greater than on treatment. Prospective studies are needed to better characterize the clinical role of amyloid PET. Neurology ® 2014;82:230-238 GLOSSARY Ab 5 b-amyloid; AD 5 Alzheimer disease; AUC 5 appropriate use criteria; CBS 5 corticobasal syndrome; CDR 5 Clinical Dementia Rating; Che-I 5 cholinesterase inhibitor; CMS 5 Centers for Medicare & Medicaid Services; DLB 5 dementia with Lewy bodies; FDG 5 fluorodeoxyglucose; FTD 5 frontotemporal dementia; MCI 5 mild cognitive impairment; PiB 5 Pittsburgh compound B; UCSF
Uploads
Papers by Jayne Hagen