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      https://www.riss.kr/link?id=A105304264

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      다국어 초록 (Multilingual Abstract)

      This study reviews evidence for the use of acetyl-choline esterase inhibitors (AChEIs) in treating Alzheimer s patients for the past decades. Even though large number of clinical trials have been conducted to prove the efficacy of these drugs in various clinical situations, questions remain to be answered due to the use of heterogeneous subject population, trial designs, and measurement tools in these studies. Many drugs with unproven clinical benefits, including vitamins, ginko biloba extracts, anti-inflammatory agents, estrogen hormone, and statins, are commonly prescribed in real-world settings for dementia patients. Despite the lack of clinical benefits statistically proven by clinical trials or meta-analyses, anecdotal dramatic improvements in some patients may foster such practices. A further look into why some patients benefit from these medications, while other don t, may shed light on future individually tailored medicine for dementia patients. This study provides a brief review of currently existing immuno-therapeutics in the hope that we can learn from the failures of the amyloid-based active and passive immunization. Issues that we need to address for the successful development of new anti-AD drugs include : 1) the brain pathology precedes clinical symptoms by several decades, 2) we need biological markers that reliably reflect cognitive or functional impairment of AD patients, and 3) we need more detailed and plausible explanations for our brain immune responses and neurodegenerative changes.
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      This study reviews evidence for the use of acetyl-choline esterase inhibitors (AChEIs) in treating Alzheimer s patients for the past decades. Even though large number of clinical trials have been conducted to prove the efficacy of these drugs in vario...

      This study reviews evidence for the use of acetyl-choline esterase inhibitors (AChEIs) in treating Alzheimer s patients for the past decades. Even though large number of clinical trials have been conducted to prove the efficacy of these drugs in various clinical situations, questions remain to be answered due to the use of heterogeneous subject population, trial designs, and measurement tools in these studies. Many drugs with unproven clinical benefits, including vitamins, ginko biloba extracts, anti-inflammatory agents, estrogen hormone, and statins, are commonly prescribed in real-world settings for dementia patients. Despite the lack of clinical benefits statistically proven by clinical trials or meta-analyses, anecdotal dramatic improvements in some patients may foster such practices. A further look into why some patients benefit from these medications, while other don t, may shed light on future individually tailored medicine for dementia patients. This study provides a brief review of currently existing immuno-therapeutics in the hope that we can learn from the failures of the amyloid-based active and passive immunization. Issues that we need to address for the successful development of new anti-AD drugs include : 1) the brain pathology precedes clinical symptoms by several decades, 2) we need biological markers that reliably reflect cognitive or functional impairment of AD patients, and 3) we need more detailed and plausible explanations for our brain immune responses and neurodegenerative changes.

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      참고문헌 (Reference)

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      2 Petersen RC, "Vitamin E and donepezil for the treatment of mild cognitive impairment" 352 : 2379-2388, 2005

      3 Cummings JL, "Use of cholinesterase inhibitors in clinical practice : evidence-based recommendations" 11 : 131-145, 2003

      4 Salloway S, "Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease" 370 : 322-333, 2014

      5 Anand R, "Therapeutics of Alzheimer’s disease:past, present and future" 76 : 27-50, 2014

      6 Wang J, "The levels of soluble versus insoluble brain Abeta distinguish Alzheimer’s disease from normal and pathologic aging" 158 : 328-337, 1999

      7 Bartus RT, "The cholinergic hypothesis of geriatric memory dysfunction" 217 : 408-414, 1982

      8 Orrego F, "The chemical nature of the main central excitatory transmitter : a critical appraisal based upon release studies and synaptic vesicle localization" 56 : 539-555, 1993

      9 Davis KL, "The Tacrine Collaborative Study Group. A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer’s disease" 327 : 1253-1259, 1992

      10 Sano M, "The Alzheimer’s Disease Cooperative Study. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease" 336 : 1216-1222, 1997

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      14 Reines SA, "Rofecoxib Protocol 091 Study Group. Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study" 62 : 66-71, 2004

      15 Feldman HH, "Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease : LEADe" 74 : 956-964, 2010

      16 Mendez MF, "Preliminary findings : behavioral worsening on donepezil in patients with frontotemporal dementia" 15 : 84-87, 2007

      17 Stinton C, "Pharmacological management of lewy body dementia : a systematic review and meta-analysis" 172 : 731-742, 2015

      18 Freund-Levi Y, "Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease : omegAD study : a randomized double-blind trial" 63 : 1402-1408, 2006

      19 Howard R, "Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer’s Disease(DOMINO-AD)trial : secondary and post-hoc analyses" 14 : 1171-1181, 2015

      20 Rigaud AS, "No additional benefit of HRT on response to rivastigmine in menopausal women with AD" 60 : 148-149, 2003

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      22 Langa KM, "Mixed dementia : emerging concepts and therapeutic implications" 292 : 2901-2908, 2004

      23 Tariot PN, "Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil : a randomized controlled trial" 291 : 317-324, 2004

      24 Porsteinsson AP, "Memantine treatment in patients with mild to moderate Alzheimer’s disease already receiving a cholinesterase inhibitor:a randomized, double-blind, placebo-controlled trial" 5 : 83-89, 2008

      25 Reisberg B, "Memantine in moderate-to-severe Alzheimer’s disease" 348 : 1333-1341, 2003

      26 McShane R, "Memantine for dementia" CD003154-, 2006

      27 Lopez OL, "Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease" 80 : 600-607, 2009

      28 Atri A, "Long-term course and effectiveness of combination therapy in Alzheimer disease" 22 : 209-221, 2008

      29 Schneider LS, "Lack of evidence for the efficacy of memantine in mild Alzheimer disease" 68 : 991-998, 2011

      30 Craft S, "Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment : a pilot clinical trial" 69 : 29-38, 2012

      31 Rogers J, "Inflammation and Alzheimer’s disease pathogenesis" 17 : 681-686, 1996

      32 Cagnin A, "In-vivo measurement of activated microglia in dementia" 358 : 461-467, 2001

      33 LeBlanc ES, "Hormone replacement therapy and cognition : systematic review and meta-analysis" 285 : 1489-1499, 2001

      34 Asthana S, "High-dose estradiol improves cognition for women with AD : results of a randomized study" 57 : 605-612, 2001

      35 Aisen PS, "High-dose B vitamin supplementation and cognitive decline in Alzheimer disease : a randomized controlled trial" 300 : 1774-1783, 2008

      36 Danysz W, "Glycine and N-methyl-D-aspartate receptors : physiological significance and possible therapeutic applications" 50 : 597-664, 1998

      37 Lancelot E, "Glutamate toxicity in chronic neurodegenerative disease" 116 : 331-347, 1998

      38 Birks J, "Ginkgo biloba for cognitive impairment and dementia" CD003120-, 2007

      39 Kertesz A, "Galantamine in frontotemporal dementia and primary progressive aphasia" 25 : 178-185, 2008

      40 Henderson VW, "Estrogen, cognition, and a woman’s risk of Alzheimer’s disease" 103 : 11S-18S, 1997

      41 Mulnard RA, "Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer’s Disease Cooperative Study" 283 : 1007-1015, 2000

      42 Shumaker SA, "Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women : the Women’s Health Initiative Memory Study : a randomized controlled trial" 289 : 2651-2662, 2003

      43 Henderson VW, "Estrogen for Alzheimer’s disease in women: randomized, double-blind, placebo-controlled trial" 54 : 295-301, 2000

      44 Salloway S, "Efficacy of donepezil in mild cognitive impairment : a randomized placebo-controlled trial" 63 : 651-657, 2004

      45 Wang HF, "Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis" 86 : 135-143, 2015

      46 Aisen PS, "Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression : a randomized controlled trial" 289 : 2819-2826, 2003

      47 Ancoli-Israel S, "Effects of galantamine versus donepezil on sleep in patients with mild to moderate Alzheimer disease and their caregivers: a double-blind, head-to-head, randomized pilot study" 19 : 240-245, 2005

      48 Wang PN, "Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study" 54 : 2061-2066, 2000

      49 Fox NC, "Effects of Abeta immunization(AN1792)on MRI measures of cerebral volume in Alzheimer disease" 64 : 1563-1572, 2005

      50 Raina P, "Effectiveness of cholinesterase inhibitors and memantine for treating dementia : evidence review for a clinical practice guideline" 148 : 379-397, 2008

      51 Farlow MR, "Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer’s disease: a 24-week, randomized, double-blind study" 32 : 1234-1251, 2010

      52 Dysken MW, "Effect of vitamin E and memantine on functional decline in Alzheimer disease : the TEAM-AD VA cooperative randomized trial" 311 : 33-44, 2014

      53 Pariente A, "Effect of treatment gaps in elderly patients with dementia treated with cholinesterase inhibitors" 78 : 957-963, 2012

      54 Van Gool WA, "Effect of hydroxychloroquine on progression of dementia in early Alzheimer’s disease: an 18-month randomised, double-blind, placebo-controlled study" 358 : 455-460, 2001

      55 Bullock R, "Effect of age on response to rivastigmine or donepezil in patients with Alzheimer’s disease" 22 : 483-494, 2006

      56 Doody RS, "Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial" 72 : 1555-1561, 2009

      57 Howard R, "Donepezil and memantine for moderate-to-severe Alzheimer’s disease" 366 : 893-903, 2012

      58 Quinn JF, "Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease : a randomized trial" 304 : 1903-1911, 2010

      59 Andersen K, "Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer’s disease? The Rotterdam Study" 45 : 1441-1445, 1995

      60 Kim DH, "Dementia medications and risk of falls, syncope, and related adverse events: metaanalysis of randomized controlled trials" 59 : 1019-1031, 2011

      61 Ridha BH, "Delusions and hallucinations in dementia with Lewy bodies : worsening with memantine" 65 : 481-482, 2005

      62 Qaseem A, "Current pharmacologic treatment of dementia : a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians" 148 : 370-378, 2008

      63 Firuzi O, "Coxibs and Alzheimer’s disease: should they stay or should they go?" 59 : 219-228, 2006

      64 Espeland MA, "Conjugated equine estrogens and global cognitive function in postmenopausal women : Women’s Health Initiative Memory Study" 291 : 2959-2968, 2004

      65 Rainer M, "Cognitive relapse after discontinuation of drug therapy in Alzheimer’s disease : cholinesterase inhibitors versus nootropics" 108 : 1327-1333, 2001

      66 Gilman S, "Clinical effects of Abeta immunization(AN1792)in patients with AD in an interrupted trial" 64 : 1553-1562, 2005

      67 Rolinski M, "Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson’s disease dementia and cognitive impairment in Parkinson’s disease" CD006504-, 2012

      68 Birks J., "Cholinesterase inhibitors for Alzheimer’s disease" CD005593-, 2006

      69 O’Regan J, "Cholinesterase inhibitor discontinuation in patients with Alzheimer’s disease: a meta-analysis of randomized controlled trials" 76 : e1424-e1431, 2015

      70 Kang SJ, "Caregiver-Administered Neuropsychiatric Inventory(CGA-NPI)" 17 : 32-35, 2004

      71 Lee JY, "Brief screening for mild cognitive impairment in elderly outpatient clinic : validation of the Korean version of the Montreal Cognitive Assessment" 21 : 104-110, 2008

      72 Cummings JL, "Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment" 67 : 57-63, 2006

      73 Sparks DL, "Atorvastatin for the treatment of mild to moderate Alzheimer disease : preliminary results" 62 : 753-757, 2005

      74 Daiello LA, "Association of fish oil supplement use with preservation of brain volume and cognitive function" 11 : 226-235, 2015

      75 Jaturapatporn D, "Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer’s disease" CD006378-, 2012

      76 AD2000 Collaborative Group, "Aspirin in Alzheimer’s disease(AD2000) : a randomised open-label trial" 7 : 41-49, 2008

      77 Galasko DR, "Antioxidants for Alzheimer disease : a randomized clinical trial with cerebrospinal fluid biomarker measures" 69 : 836-841, 2012

      78 Patton RL, "Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer’s disease patients : a biochemical analysis" 169 : 1048-1063, 2006

      79 Kornhuber J, "Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties" 43 : 91-104, 1994

      80 Cummings J, "Alzheimer’s disease drug development pipeline: 2017" 3 : 367-384, 2017

      81 Campbell NL, "Adherence and tolerability of Alzheimer’s Disease medications : a pragmatic randomized trial" 65 : 1497-1504, 2017

      82 Soysal P, "Acetylcholinesterase inhibitors are associated with weight loss in older people with dementia : a systematic review and meta-analysis" 87 : 1368-1374, 2016

      83 Winblad B, "A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer’s disease--rivastigmine patch versus capsule" 22 : 456-467, 2007

      84 Sano M, "A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease" 77 : 556-563, 2011

      85 Jonsson T, "A mutation in APP protects against Alzheimer’s disease and agerelated cognitive decline" 488 : 96-99, 2012

      86 Wilcock G, "A long-term comparison of galantamine and donepezil in the treatment of Alzheimer’s disease" 20 : 777-789, 2003

      87 Scharf S, "A doubleblind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease" 53 : 197-201, 1999

      88 Reisberg B, "A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease" 63 : 49-54, 2006

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