Diagnosis and Treatment of Clinical Alzheimer's-type Dementia (CATD): A Systematic Review

Project Summary Title and Description

Title
Diagnosis and Treatment of Clinical Alzheimer's-type Dementia (CATD): A Systematic Review
Description
The ultimate reason for accurately diagnosing clinical Alzheimer’s-type dementia (CATD) and whether Alzheimer’s disease (AD) is the underlying neuropathological etiology is to inform decision making about drug and nondrug treatments to improve patient and caregiver outcomes. In individuals with suspected cognitive impairment, comprehensive neuropsychological testing may help clinically diagnose dementia and distinguish between dementia subtypes. However, such testing is time consuming and access is limited in some clinical settings. Therefore, we need better understanding in this population with suspected cognitive impairment (case finding) which brief cognitive tests and test combinations most accurately distinguish patients with CATD from those with normal cognition or mild cognitive impairment (MCI), and whether patient characteristics affect test classification accuracy. Additionally, many individuals clinically diagnosed with CATD do not meet neuropathologic (gold standard) criteria for AD on post-mortem brain autopsy. Therefore, we also need better understanding of how accurate pre-mortem brain imaging and cerebrospinal fluid (CSF) biomarkers are for distinguishing patients whose dementia is due to AD from those with non-AD dementia, and whether classification accuracy varies depending on patient characteristics. Finally, although only a few prescription drugs are approved by the U.S. Food and Drug Administration (FDA) for CATD, many supplements are promoted for cognition and function. In addition, many prescription drugs are used off-label for CATD-associated behavioral and psychological symptoms of dementia (BPSD), including antipsychotics despite FDA black box warnings about their increased mortality risk in this population. Less is understood about the beneficial and harmful effects of supplements for CATD-associated BPSD. To guide CATD treatment decisions for cognition, function, BPSD and other outcomes, we need to clarify the benefits and harms of prescription drugs and supplements in this population.
Attribution
MN EPC
Authors of Report
Howard A. Fink, M.D., MPH Laura S. Hemmy, Ph.D. Eric J. Linskens, B.S. Pombie C. Silverman, B.A. Roderick MacDonald, M.S. J. Riley McCarten, M.D. Kristine M.C. Talley, Ph.D., R.N., G.N.P.-B.C., F.G.S.A. Priyanka J. Desai, M.S.P.H. Mary L. Forte, Ph.D., D.C. Margaret A. Miller, M.A. Michelle Brasure, Ph.D., M.S.P.H., M.L.I.S. Victoria A. Nelson, M.Sc. Brent C. Taylor, Ph.D., M.P.H. Weiwen Ng, M.P.H. Jeannine M. Ouellette, M.F.A. Nancy L. Greer, Ph.D. Kerry M. Sheets, M.D. Timothy J. Wilt, M.D., M.P.H. Mary Butler, Ph.D., M.B.A.
Methodology description
Systematic Review
PROSPERO
N/A
DOI
N/A
Notes
Appendix E: Tables for KQ 3 - Efficacy and Harms of Prescription Drug Treatment vs. Placebo for Cognition, Function, and Quality of Life (Characteristics of included literature, risk of bias assessments, outcomes, summaries of strength of evidence) (https://srdr.s3.amazonaws.com/uploads/08-25-2022/CATD_+Appendix+E.docx) Appendix F: Tables for KQ 4: Efficacy and Harms of Supplements vs. Placebo for Cognition, Function, and Quality of Life (Characteristics of included literature, risk of bias assessments, outcomes, summaries of strength of evidence) (https://srdr.s3.amazonaws.com/uploads/08-25-2022/CATD_+Appendix+F.docx) Appendix G: Tables for KQ 5: Comparative Effectiveness and Harms of Prescription Drug Treatment vs. Other Active Treatments for Cognition, Function, and Quality of Life (Characteristics of included literature, risk of bias assessments, outcomes, summaries of strength of evidence) (https://srdr.s3.amazonaws.com/uploads/08-25-2022/CATD_Appendix+G.docx) Appendix H: Tables for KQ 6: Efficacy and Harms of Prescription Drug Treatment vs. Placebo for Behavioral and Psychological Symptoms of Dementia (BPSD) (Characteristics of included literature, risk of bias assessments, outcomes, summaries of strength of evidence) (https://srdr.s3.amazonaws.com/uploads/08-25-2022/CATD_Appendix+H.docx) Appendix I: Tables for KQ 7: Efficacy and Harms of Supplements vs. Placebo for Behavioral and Psychological Symptoms of Dementia (BPSD) (Characteristics of included literature, risk of bias assessments, outcomes, summaries of strength of evidence) (https://srdr.s3.amazonaws.com/uploads/08-25-2022/CATD_Appendix+I.docx) Appendix J: Tables for KQ 8: Comparative Effectiveness and Harms of Prescription Drug Treatment vs. Other Active Treatment for Behavioral and Psychological Symptoms of Dementia (BPSD) (Characteristics of included literature, risk of bias assessments, outcomes, summaries of strength of evidence) (https://srdr.s3.amazonaws.com/uploads/08-25-2022/CATD_Appendix+J.docx)
Funding Source
Agency for Healthcare Research and Quality (AHRQ), Rockville, MD

Key Questions

1. KQ3: In adults with CATD, what are the efficacy and harms of prescription drug interventions versus placebo/inactive control for treatment of cognition, function and quality of life? KQ 3a: Does the efficacy of prescription drug interventions versus placebo/inactive control vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, living setting)?
2. KQ 5:In adults with CATD, what are the comparative effectiveness and harms of prescription drug interventions versus other active interventions for treatment of cognition, function, and quality of life? KQ 5a: Of prescription drug interventions versus other prescription drug interventions? KQ 5b: Of prescription drug interventions versus supplements? KQ 5c: Of prescription drug interventions versus nondrug interventions (e.g., exercise, cognitive training, caregiver social support)? KQ 5d: Does the comparative effectiveness of prescription drug interventions versus other active interventions for treatment of cognition, function, and quality of life vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, living setting)?
3. KQ 6:In adults with CATD and behavioral and psychological symptoms of dementia (BPSD), what are the efficacy and harms of prescription drug interventions versus placebo/inactive control for treatment of BPSD? KQ 6a: For reducing frequency and severity of future BPSD? KQ 6b: Does the efficacy of prescription drug interventions versus placebo/inactive control for reducing frequency and severity of future BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)? KQ 6c: For acute treatment of BPSD? KQ 6d: Does the efficacy of prescription drug interventions versus placebo/inactive control for acute treatment of BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)?
4. KQ 4: In adults with CATD, what are the efficacy and harms of supplements versus placebo/inactive control for treatment of cognition, function, and quality of life? KQ 4a: Does the efficacy of supplements versus placebo/inactive control vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, living setting)?
5. KQ8:In adults with CATD and BPSD, what are the comparative effectiveness and harms of prescription drug interventions versus other active interventions for treatment of BPSD? KQ 8a: Of prescription drug interventions versus other prescription drug interventions for reducing frequency and severity of future BPSD? KQ 8b: Of prescription drug interventions versus supplements for reducing frequency and severity of future BPSD? KQ 8c: Of prescription drug interventions versus nondrug interventions for reducing frequency and severity of future BPSD? KQ 8d: Does the comparative effectiveness of prescription drug interventions versus other active interventions for reducing frequency and severity of future BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)? KQ 8e: Of prescription drug interventions versus other prescription drug interventions for acute treatment of BPSD? KQ 8f: Of prescription drug interventions versus supplements for acute treatment of BPSD? KQ 8g: Of prescription drug interventions versus nondrug interventions for acute treatment of BPSD? KQ 8h: Does the comparative effectiveness of prescription drug interventions versus other active interventions for acute treatment of BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)?
6. KQ 7: In adults with CATD and BPSD, what are the efficacy and harms of supplements versus placebo/inactive control for treatment of BPSD in adults with CATD and BPSD? KQ 7a: For reducing frequency and severity of future BPSD? KQ 7b: Does the efficacy of supplements versus placebo/inactive control for reducing frequency and severity of future BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)? KQ 7c: For acute treatment of BPSD? KQ 7d: Does the efficacy of supplements versus placebo/inactive control for acute treatment of BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Effects of 6 months of treatment with donepezil and rivastigmine on results of neuropsychological tests of MMSE, NPI, Clock and Bender in patients with Alzheimer's diseaseAbolfazli, R;Ghazanshahi, S;Nazeman, M2008
An open-label, comparative study of rivastigmine, donepezil and galantamine in a real-world settingAguglia, E.;Onor, M. L.;Saina, M.;Maso, E.2004
High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trialAisen, P. S.;Schneider, L. S.;Sano, M.;Diaz-Arrastia, R.;van Dyck, C. H.;Weiner, M. F.;Bottiglieri, T.;Jin, S.;Stokes, K. T.;Thomas, R. G.;Thal, L. J.;Alzheimer Disease Cooperative, Study2008
Skin reactions at the application site of rivastigmine patch (4.6 mg/24 h, 9.5 mg/24 h or 13.3 mg/24 h): a qualitative analysis of clinical studies in patients with Alzheimer's diseaseAlva, G.;Cummings, J. L.;Galvin, J. E.;Meng, X.;Velting, D. M.2015
Efficacy of rivastigmine transdermal patch on activities of daily living: item responder analysesAlva, G.;Grossberg, G. T.;Schmitt, F. A.;Meng, X.;Olin, J. T.2011
Efficacy of higher-dose 13.3mg/24 h (15cm2) rivastigmine patch on the Alzheimer's Disease Assessment Scale-cognitive subscale: domain and individual item analysisAlva, G.;Isaacson, R.;Sadowsky, C.;Grossberg, G.;Meng, X.;Somogyi, M.2014
The effect of stimulation therapy and donepezil on cognitive function in Alzheimer's disease. A community based RCT with a two-by-two factorial designAndersen, F.;Viitanen, M.;Halvorsen, D. S.;Straume, B.;Wilsgaard, T.;Engstad, T. A.2012
The effects of combine treatment of memantine and donepezil on Alzheimer's disease patients and its relationship with cerebral blood flow in the prefrontal areaAraki, T.;Wake, R.;Miyaoka, T.;Kawakami, K.;Nagahama, M.;Furuya, M.;Limoa, E.;Liaury, K.;Hashioka, S.;Murotani, K.;Horiguchi, J.2014
MR spectroscopy for assessment of memantine treatment in mild to moderate Alzheimer dementiaAshford, J. W.;Adamson, M.;Beale, T.;La, D.;Hernandez, B.;Noda, A.;Rosen, A.;O'Hara, R.;Fairchild, J. K.;Spielman, D.;Yesavage, J. A.2011
Cumulative, additive benefits of memantine-donepezil combination over component monotherapies in moderate to severe Alzheimer's dementia: a pooled area under the curve analysisAtri, A.;Hendrix, S. B.;Pejovic, V.;Hofbauer, R. K.;Edwards, J.;Molinuevo, J. L.;Graham, S. M.2015
Caregiver distress related to neuropsychiatric symptoms is reduced with extended-release memantine cholinesterase inhibitor combination in patients with moderate to severe Alzheimer's diseaseAtri, A;Hendrix, S;Ellison, N;Otcheretko, V;Edwards, J2016
Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapyAtri, A.;Molinuevo, J. L.;Lemming, O.;Wirth, Y.;Pulte, I.;Wilkinson, D.2013
Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study.[Republished in J Alzheimers Dis. 2008 Feb;13(1):97-107; PMID: 18334761]Bakchine, S.;Loft, H.2007
Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study.[Republished from J Alzheimers Dis. 2007 Jul;11(4):471-9; PMID: 17656827]Bakchine, S.;Loft, H.2008
Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trialBallard, C.;Margallo-Lana, M.;Juszczak, E.;Douglas, S.;Swann, A.;Thomas, A.;O'Brien, J.;Everratt, A.;Sadler, S.;Maddison, C.;Lee, L.;Bannister, C.;Elvish, R.;Jacoby, R.2005
A double-blind randomized placebo-controlled withdrawal trial comparing memantine and antipsychotics for the long-term treatment of function and neuropsychiatric symptoms in people with Alzheimer's disease (MAIN-AD)Ballard, C.;Thomas, A.;Gerry, S.;Yu, L. M.;Aarsland, D.;Merritt, C.;Corbett, A.;Davison, C.;Sharma, N.;Khan, Z.;Creese, B.;Loughlin, P.;Bannister, C.;Burns, A.;Win, S. N.;Walker, Z.;Main-Ad investigators2015
Impact of apolipoprotein E genotypes on vitamin E and memantine treatment outcomes in Alzheimer's diseaseBelitskaya-Levy, I.;Dysken, M.;Guarino, P.;Sano, M.;Asthana, S.;Vertrees, J. E.;Pallaki, M.;Llorente, M.;Love, S.;Schellenberg, G.2018
Rivastigmine for Alzheimer's diseaseBirks, J. S.;Chong, L. Y.;Grimley Evans, J.
Donepezil for dementia due to Alzheimer's disease. [Review][Update of Cochrane Database Syst Rev. 2006 Jan 25;(1):CD001190; PMID: 16437430]Birks, J. S.;Harvey, R. J.2018
Donepezil preserves cognition and global function in patients with severe Alzheimer diseaseBlack, S. E.;Doody, R.;Li, H.;McRae, T.;Jambor, K. M.;Xu, Y.;Sun, Y.;Perdomo, C. A.;Richardson, S.2007
Galantamine prolonged-release formulation in the treatment of mild to moderate Alzheimer's diseaseBrodaty, H.;Corey-Bloom, J.;Potocnik, F. C.;Truyen, L.;Gold, M.;Damaraju, C. R.2005
Effect of age on response to rivastigmine or donepezil in patients with Alzheimer's diseaseBullock, R.;Bergman, H.;Touchon, J.;Gambina, G.;He, Y.;Nagel, J.;Lane, R.2006
Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's disease over a 2-year periodBullock, R.;Touchon, J.;Bergman, H.;Gambina, G.;He, Y.;Rapatz, G.;Nagel, J.;Lane, R.2005
Safety and efficacy of galantamine (Reminyl) in severe Alzheimer's disease (the SERAD study): a randomised, placebo-controlled, double-blind trialBurns, A.;Bernabei, R.;Bullock, R.;Cruz Jentoft, A. J.;Frolich, L.;Hock, C.;Raivio, M.;Triau, E.;Vandewoude, M.;Wimo, A.;Came, E.;Van Baelen, B.;Hammond, G. L.;van Oene, J. C.;Schwalen, S.2009
The effects of donepezil in Alzheimer's disease - results from a multinational trialBurns, A.;Rossor, M.;Hecker, J.;Gauthier, S.;Petit, H.;Moller, H. J.;Rogers, S. L.;Friedhoff, L. T.1999
Efficacy of rivastigmine in subjects with moderately severe Alzheimer's diseaseBurns, A.;Spiegel, R.;Quarg, P.2004
Effect of cold pressed coconut oil on cognition and behavior among patients with Alzheimer's disease - A pilot intervention studyChan, S. C.;Esther, G. E.;Yip, H. L.;Sugathan, S.;Chin, P. S.2017
A double-blind randomised comparison of risperidone and haloperidol in the treatment of behavioural and psychological symptoms in Chinese dementia patientsChan, W. C.;Lam, L. C.;Choy, C. N.;Leung, V. P.;Li, S. W.;Chiu, H. F.2001
Clinical study on the treatment of Alzheimer's disease by traditional Chinese and western medicineChen, W;Liang, Jf;Jiang, Lf;Wu, L;Hu, Yq;He, Qc2015
A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's diseaseConnelly, P. J.;Prentice, N. P.;Cousland, G.;Bonham, J.2008
A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's diseaseCorey-Bloom, J.;Anand, R.;Veach, J.1998
Treatment of Alzheimer's disease with a cholinesterase inhibitor combined with antioxidantsCornelli, U.2010
Effects of rivastigmine in Alzheimer's disease patients with and without hallucinationsCummings, J.;Emre, M.;Aarsland, D.;Tekin, S.;Dronamraju, N.;Lane, R.2010
Randomized, double-blind, parallel-group, 48-week study for efficacy and safety of a higher-dose rivastigmine patch (15 vs. 10 cm2) in Alzheimer's diseaseCummings, J.;Froelich, L.;Black, S. E.;Bakchine, S.;Bellelli, G.;Molinuevo, J. L.;Kressig, R. W.;Downs, P.;Caputo, A.;Strohmaier, C.2012
Effect of donepezil on cognition in severe Alzheimer's disease: a pooled data analysisCummings, J.;Jones, R.;Wilkinson, D.;Lopez, O.;Gauthier, S.;Waldemar, G.;Zhang, R.;Xu, Y.;Sun, Y.;Richardson, S.;Mackell, J.2010
Effects of rivastigmine transdermal patch and capsule on aspects of clinical global impression of change in Alzheimer's disease: a retrospective analysisCummings, J. L.;Ferris, S. H.;Farlow, M. R.;Olin, J. T.;Meng, X.2010
Rivastigmine transdermal patch skin tolerability: results of a 1-year clinical trial in patients with mild-to-moderate Alzheimer's diseaseCummings, J. L.;Farlow, M. R.;Meng, X.;Tekin, S.;Olin, J. T.2010
Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trialDe Jesus Moreno Moreno, M.2003
Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind studyDemarin, V.;Podobnik, S. S.;Storga-Tomic, D.;Kay, G.2004
Safety and tolerability of donepezil at doses up to 20 mg/day: results from a pilot study in patients with Alzheimer's diseaseDoody, R. S.;Corey-Bloom, J.;Zhang, R.;Li, H.;Ieni, J.;Schindler, R.2008
Chronic donepezil treatment is associated with slowed cognitive decline in Alzheimer's diseaseDoody, R. S.;Dunn, J. K.;Clark, C. M.;Farlow, M.;Foster, N. L.;Liao, T.;Gonzales, N.;Lai, E.;Massman, P.2001
Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer diseaseDoody, R. S.;Geldmacher, D. S.;Gordon, B.;Perdomo, C. A.;Pratt, R. D.;Donepezil Study, Group2001
Efficacy and safety of donepezil 23 mg versus donepezil 10 mg for moderate-to-severe Alzheimer's disease: a subgroup analysis in patients already taking or not taking concomitant memantineDoody, R. S.;Geldmacher, D. S.;Farlow, M. R.;Sun, Y.;Moline, M.;Mackell, J.2012
Post hoc comparison of daily rates of nausea and vomiting with once- and twice-daily galantamine from a double-blind, placebo-controlled, parallel-group, 6-month studyDunbar, F.;Zhu, Y.;Brashear, H. R.2006
Ondansetron in the treatment of cognitive decline in Alzheimer dementiaDysken, M.;Kuskowski, M.;Love, S.;Ondansetron Study, Group2002
Pooled analyses on cognitive effects of memantine in patients with moderate to severe Alzheimer's diseaseEmre, M.;Mecocci, P.;Stender, K.2008
Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer's Disease Patients During Oral Omega-3 Fatty Acid Supplementation: The OmegAD StudyEriksdotter, M.;Vedin, I.;Falahati, F.;Freund-Levi, Y.;Hjorth, E.;Faxen-Irving, G.;Wahlund, L. O.;Schultzberg, M.;Basun, H.;Cederholm, T.;Palmblad, J.2015
Rivastigmine in patients with Alzheimer's disease and concurrent hypertensionErkinjuntti, T.;Skoog, I.;Lane, R.;Andrews, C.2002
Effects of oral rivastigmine on cognitive domains in mild-to-moderate Alzheimer's diseaseFarlow, M. R.;Cummings, J. L.;Olin, J. T.;Meng, X.2010
The effect of vascular risk factors on the efficacy of rivastigmine patch and capsule treatment in Alzheimer's diseaseFarlow, M. R.;Doraiswamy, P. M.;Meng, X.;Cooke, K.;Somogyi, M.2011
Memantine for the treatment of Alzheimer's disease: tolerability and safety data from clinical trialsFarlow, M. R.;Graham, S. M.;Alva, G.2008
Rivastigmine transdermal patch and capsule in Alzheimer's disease: influence of disease stage on response to therapyFarlow, M. R.;Grossberg, G. T.;Meng, X.;Olin, J.;Somogyi, M.2011
A 24-week, randomized, controlled trial of rivastigmine patch 13.3 mg/24 h versus 4.6 mg/24 h in severe Alzheimer's dementiaFarlow, M. R.;Grossberg, G. T.;Sadowsky, C. H.;Meng, X.;Somogyi, M.2013
Evaluating Response to High-Dose 13.3 mg/24 h Rivastigmine Patch in Patients with Severe Alzheimer's DiseaseFarlow, Martin R.;Sadowsky, C. H.;Velting, D. M.;Meng, X.;Islam, M. Z.2015
Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer's diseaseFarlow, M.;Veloso, F.;Moline, M.;Yardley, J.;Brand-Schieber, E.;Bibbiani, F.;Zou, H.;Hsu, T.;Satlin, A.2011
Comparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer's disease: a double-blind randomized clinical trialFarokhnia, M.;Shafiee Sabet, M.;Iranpour, N.;Gougol, A.;Yekehtaz, H.;Alimardani, R.;Farsad, F.;Kamalipour, M.;Akhondzadeh, S.2014
A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease.[Erratum appears in Neurology 2001 Dec 11;57(11):2153]Feldman, H.;Gauthier, S.;Hecker, J.;Vellas, B.;Subbiah, P.;Whalen, E.;Donepezil, Msad Study Investigators Group2001
Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden.[Erratum appears in J Am Geriatr Soc. 2003 Sep;51(9):1331]Feldman, H.;Gauthier, S.;Hecker, J.;Vellas, B.;Emir, B.;Mastey, V.;Subbiah, P.;Donepezil, Msad Study Investigators Group2003
Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trialFeldman, H.;Gauthier, S.;Hecker, J.;Vellas, B.;Xu, Y.;Ieni, J. R.;Schwam, E. M.;Donepezil, Msad Study Investigators Group2005
Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer's diseaseFeldman, H. H.;Lane, R.;Study, Group2007
Activities of daily living in moderate-to-severe Alzheimer disease: an analysis of the treatment effects of memantine in patients receiving stable donepezil treatmentFeldman, H. H.;Schmitt, F. A.;Olin, J. T.;Memantine, M. E. M. M. D. Study Group2006
Effects of donepezil 23 mg on Severe Impairment Battery domains in patients with moderate to severe Alzheimer's disease: evaluating the impact of baseline severityFerris, S.;Cummings, J.;Christensen, D.;Doody, R.;Farlow, M.;Sabbagh, M.;Liu, L.;Mackell, J.;Fain, R.2013
Analyzing the impact of 23 mg/day donepezil on language dysfunction in moderate to severe Alzheimer's diseaseFerris, S. H.;Schmitt, F. A.;Saxton, J.;Richardson, S.;Mackell, J.;Sun, Y.;Xu, Y.2011
Treatment effects of Memantine on language in moderate to severe Alzheimer's disease patientsFerris, S.;Ihl, R.;Robert, P.;Winblad, B.;Gatz, G.;Tennigkeit, F.;Gauthier, S.2009
Cognitive efficacy of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch in severe Alzheimer's disease: severe impairment battery factor analysisFerris, S;Isaacson, R;Velting, D;Meng, X2014
Rivastigmine in moderately severe-to-severe Alzheimer's disease: Severe Impairment Battery factor analysisFerris, S.;Karantzoulis, S.;Somogyi, M.;Meng, X.2013
Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older: Findings from a randomized controlled trialFields, Cynthia;Drye, Lea;Vaidya, Vijay;Lyketsos, Constantine2012
Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trialFreund-Levi, Y.;Eriksdotter-Jonhagen, M.;Cederholm, T.;Basun, H.;Faxen-Irving, G.;Garlind, A.;Vedin, I.;Vessby, B.;Wahlund, L. O.;Palmblad, J.2006
Functional, cognitive and behavioral effects of donepezil in patients with moderate Alzheimer's diseaseGauthier, S.;Feldman, H.;Hecker, J.;Vellas, B.;Emir, B.;Subbiah, P.;Donepezil, Msad Study Investigators' Group2002
Cognitive Effects of Soy Isoflavones in Patients with Alzheimer's DiseaseGleason, C. E.;Fischer, B. L.;Dowling, N. M.;Setchell, K. D.;Atwood, C. S.;Carlsson, C. M.;Asthana, S.2015
Efficacy of higher dose 13.3 mg/24 h rivastigmine patch on instrumental activities of daily living in patients with mild-to-moderate Alzheimer's diseaseGrossberg, G.;Cummings, J.;Frolich, L.;Bellelli, G.;Molinuevo, J. L.;Krahnke, T.;Strohmaier, C.2013
Rivastigmine in Alzheimer disease: efficacy over two years.[Erratum appears in Am J Geriatr Psychiatry. 2004 Nov-Dec;12(6):679]Grossberg, G.;Irwin, P.;Satlin, A.;Mesenbrink, P.;Spiegel, R.2004
Effects of transdermal rivastigmine on ADAS-Cog items in mild-to-moderate Alzheimer's diseaseGrossberg, Gt;Schmitt, Fa;Xiangyi, Meng;Tekin, S;Olin, J2010
Memantine ER Maintains Patient Response in Moderate to Severe Alzheimer's Disease: Post Hoc Analyses From a Randomized, Controlled, Clinical Trial of Patients Treated With Cholinesterase InhibitorsGrossberg, G. T.;Alva, G.;Hendrix, S.;Ellison, N.;Kane, M. C.;Edwards, J.2018
Evaluating high-dose rivastigmine patch in severe Alzheimer's disease: analyses with concomitant memantine usage as a factorGrossberg, G. T.;Farlow, M. R.;Meng, X.;Velting, D. M.2015
The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer's disease taking cholinesterase inhibitorsGrossberg, G. T.;Manes, F.;Allegri, R. F.;Gutierrez-Robledo, L. M.;Gloger, S.;Xie, L.;Jia, X. D.;Pejovic, V.;Miller, M. L.;Perhach, J. L.;Graham, S. M.2013
Dose effects associated with rivastigmine transdermal patch in patients with mild-to-moderate Alzheimer's diseaseGrossberg, G. T.;Olin, J. T.;Somogyi, M.;Meng, X.2011
Lack of adverse pharmacodynamic drug interactions with rivastigmine and twenty-two classes of medicationsGrossberg, G. T.;Stahelin, H. B.;Messina, J. C.;Anand, R.;Veach, J.2000
Reviews: Effects of transdermal rivastigmine on ADAS-Cog items in mild-to-moderate Alzheimer's diseaseGrossberg, George T.;Schmitt, Frederick A.;Meng, Xiangyi;Tekin, Sibel;Olin, Jason2010
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Effect of concomitant use of memantine on mortality and efficacy outcomes of galantamine-treated patients with Alzheimer's disease: post-hoc analysis of a randomized placebo-controlled studyHager, K.;Baseman, A. S.;Nye, J. S.;Brashear, H. R.;Han, J.;Sano, M.;Davis, B.;Richards, H. M.2016
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