Objective-To examine whether the presence of motor signs has predictive value for important outcomes in Alzheimer disease (AD). Methods-A total of 533 patients with AD at early stages (mean Folstein Mini-Mental StateExamination [MMSE] 21/30 at entry) were recruited and followed semiannually for up to 13.1 years (mean 3) in five University-based AD centers in the United States and European Union. Four outcomes, assessed every 6 months, were used in Cox models: cognitive endpoint (Columbia Mini-Mental State Examination ≤ 20/57 [∼MMSE ≤ 10/30]), functional endpoint (Blessed Dementia Rating Scale ≥ 10), institutionalization equivalent index, and death. Using a standardized portion of the Unified PD Rating Scale (administered every 6 months for a total of 3,149 visit-assessments, average 5.9 per patient), the presence of motor signs, as well as of individual motor sign domains, was examined as time-dependent predictor. The models controlled for cohort, recruitment center, sex, age, education, a comorbidity index, and baseline cognitive and functional performance.Results-A total of 39% of the patients reached the cognitive, 41% the functional, 54% the institutionalization, and 47% the mortality endpoint. Motor signs were noted for 14% of patients at baseline and for 45% at any evaluation. Their presence was associated with increased risk for cognitive decline (RR, 1.72; 95% CI, 1.24 to 2.38), functional decline (1.80 [1.33 to 2.45]), institutionalization (1.68 [1.26 to 2.25]), and death (1.38 [1.05 to 1.82]). Tremor was associated with increased risk for reaching the cognitive and bradykinesia for reaching the functional endpoints. Postural-gait abnormalities carried increased risk for institutionalization and mortality. Faster rates of motor sign accumulation were associated with increased risk for all outcomes.Conclusions-Motor signs predict cognitive and functional decline, institutionalization, and mortality in Alzheimer disease. Different motor sign domains predict different outcomes.Motor signs are commonly observed in Alzheimer disease (AD). [1][2][3][4] Because their exact mechanism and anatomic location of origin is not clear, in this article we use the term motor Address correspondence and reprint requests to Dr. Nikolaos Scarmeas, Columbia University Medical Center, 622 West 168th street, PH 19th floor, New York, NY 10032; ns257@columbia.edu. NIH Public Access Author ManuscriptNeurology. Author manuscript; available in PMC 2011 January 27. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript signs to refer to what is usually described in the literature as extrapyramidal signs or parkinsonian signs or parkinsonism.As compared to patients with AD without motor signs, patients with AD with motor signs have higher annual total cost of care. 5 In addition, information about presence of motor signs in AD is important because they may predict cognitive 6-9 and functional 2,10 decline, institutionalization, 2,10 and death. [10][11][12][13][14][15][16] However, some reports failed to d...

Background-Psychiatric symptoms occur frequently in the course of AD, are a frequent contributor to institutionalization, predict cognitive decline and death, and often require treatment with psychotropic medications. Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results.

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma has a poor prognosis, with a median survival of 5 to 8 months without treatment. Response and survival after chemoembolization were evaluated. METHODS: Lobar or segmental chemoembolization with cisplatinum, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol particles was performed at monthly intervals for 1-4 sessions until the entire intrahepatic tumor burden was treated. Cross-sectional imaging and clinical and laboratory evaluation were performed before treatment, 1 month after treatment, and then every 3 months. A second cycle of treatment was performed for intrahepatic recurrence. Toxicity was assessed using NCI CTC v.3.0. Response was evaluated using RECIST criteria, and survival was estimated with Kaplan-Meier analysis. RESULTS: Sixty-two patients were treated. Thirty-seven had pathologically proven cholangiocarcinoma, and 25 had poorly differentiated adenocarcinoma of unknown primary, likely cholangiocarcinoma. One hundred and twenty-two total procedures were performed during the initial cycle of treatment (mean, 2.0 per patient). Twenty patients received a second cycle, for a total of 165 procedures. There were 5 major complications. Thirty-day diseasespecific mortality was 0%. Forty-five of 62 patients were evaluable for morphologic response after completion of their initial cycle: 11% (n ¼ 5) partial responses, 64% (n ¼ 29) stable, and 24% (n ¼ 11) progressed. Median time to progression from first chemoembolization was 8 months, with 28% free of progression at 12 months. Median survival from time of diagnosis was 20 months, with 1-, 2-, and 3-year survival of 75%, 39%, and 17%, respectively. Median survival from time of first chemoembolization was 15 months, with 1-, 2-, and 3-year survival of 61%, 27%, and 8%, respectively. There was no statistically significant difference in survival between patients with cholangiocarcinoma and those with poorly differentiated adenocarcinoma. Patients who also received systemic chemotherapy had improved overall survival (median 28 vs 16 months, P ¼ .02; HR, 1.94; 95% CI, 1.13-3.33). CONCLUSIONS: Chemoembolization provided local disease control (PR þ SD) of intrahepatic cholangiocarcinoma and adenocarcinoma of unknown primary in 76%. Overall survival after chemoembolization showed the best outcomes for those receiving multidisciplinary integrated liver-directed and systemic therapies.

BACKGROUND: Unresectable colorectal liver metastases have a 1-and 2-year survival of 55% and 33% with current systemic therapies. The authors evaluated response and survival after transarterial chemoembolization. METHODS: Chemoembolization with cisplatin, doxorubicin, mitomycin C, ethiodized oil, and polyvinyl alcohol particles was performed at monthly intervals for 1 to 4 sessions. Cross-sectional imaging and clinical and laboratory evaluation were performed before treatment, 1 month after treatment, and then every 3 months. A second cycle was performed for intrahepatic recurrence. Toxicity was assessed using National Cancer Institute's Common Toxicity Criteria version 3.0. Response was evaluated using Response Evaluation Criteria in Solid Tumors criteria. Progression and survival were estimated with Kaplan-Meier analysis. RESULTS: A total of 245 treatments were performed over 141 cycles on 121 patients. Ninety-five of 141 treatment cycles were evaluable for response: 2 (2%) partial response, 39 (41%) stable disease, and 54 (57%) progression. Median time to disease progression (TTP) in the treated liver was 5 months, and median TTP anywhere was 3 months. Median survival was 33 months from diagnosis of the primary colon cancer, 27 months from development of liver metastases, and 9 months from chemoembolization. Survival was significantly better when chemoembolization was performed after first-or second-line systemic therapy (11-12 months) than after third-to fifth-line therapies (6 months) (P ¼ .03). Presence of extrahepatic metastases did not adversely affect survival (P ¼ .48). CONCLUSIONS: Chemoembolization provided local disease control of hepatic metastases after 43% of treatment cycles. Median survival was 27 months overall, and 11 months when initiated for salvage after failure of second-line systemic therapy. Cancer 2011;117:343-52.

No abstract