investigational therapies for treatment of Alzheimer's disease
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Comparative biology
in vitro studies
- certain NSAIDS diminish formation of Abeta42[6][13][14]
- flurbiprofen, ibuprofen, mecofenamate indomethacin, sulindac, fenoprofen, & diclofenac do
- aspirin, naproxen, celecoxib don't
- inhibition via direct interaction with gamma-secretase[13][14]
- inhibition of Abeta42 formation in favor of Abeta38
- simvastatin allegedly diminishes formation of Abeta42 formation[17] (also see statins & Alzheimer's disease)
- acetylcholinesterase may act as a nucleating factor to promote conversion of soluble amyloid peptide into insoluble amyloid fibrils[11]
- a peripheral site rather than the active site of the enzyme is thought to mediate the interaction (based on X-ray crystallography)
- inhibition of this interaction is proposed as a target for pharmaceutical intervention
- disruption of amyloid beta-pleated sheets[12]
- linking Abeta with chaperone using a small bivalent molecule prevents aggregation of Abeta & eliminates Abeta toxicity[19]
- resveratrol promotes intracellular degradation of Abeta via a mechanism involving the proteasome[24]
- docosahexaenoic acid (DHA)-derived 10,17S-docosatriene NPD1 promotes neuron survival via the induction of antiapoptotic & neuroprotective gene-expression programs that suppress Abeta42-induced neurotoxicity[25]
- calorie restriction & resveratrol activate SIRT1, SIRT1 inhibits ROCK1, which in turn, increases APP alpha-secretase activity[34]
studies in rodents
- immunization with Abeta42 or passive immunization with A-beta(1-42) antibodies
- protected mice genetically engineered to overproduce Abeta42 from developing amyloid plaques[1][2]
- attenuated learning defects associated with plaques[3]
- an inhibitor of acyl-cholesterol acyltransferase (ACAT) reduces accumulation of amyloid plaques & Abeta levels in a mouse-model for Alzheimer's disease[20]
- inhibitors of diacylglycerol O-acyltransferase 1 (DGAT1) enhance beta peptide & amyloid plaque removal in a mouse model for Alzheimer's disease
- curcumin diminishes amyloid in a mouse model for AD[27]
- DHA (omega-3) diminishes amyloid in a mouse model for AD[7]
- anti-oxidant 'cocktails' have been proposed[7]
- doxycyline beginning at 6 months of age diminished APP expression & Abeta production & stopped progression of amyloid pathology in APP transgenic mice, but resulted in little clearance of preexisting amyloid plaques[28]
- inositol 30 mg/kg/day reduces amyloid pathology & improves behavioral manifestations of Abeta aggregation in a transgenic mouse model for Alzheimer's disease[29]
- muscarinic M1 receptor agonist AF267B reduced Abeta & tau pathology in hippocampus & cerebral cortex, but not amygadla in a transgenic mouse model for AD[30]
- caloric restriction attenuates beta-amyloid neuropathology in a mouse model of Alzheimer's disease[37]
- pomegranate juice decreases amyloid load & improves behavior in a mouse model of Alzheimer's disease[32]
- Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease[33]
- LRP-IV (an LRP1 fragment) clears amyloid in a mouse-model of Alzheimer's disease[35], no adverse effects reported
- valsartan clears beta-amyloid & improves spatial learning in a mouse model for AD[36], <not a feature of ARBs>
- BACE1 inhibitor tethered to sterol via polyglycol diminishes pathology in APP transgenic mice[38]
- electromagnetic field treatment at standard cell phone frequencies protects against & reverses cognitive decline in a mouse model for AD (AbetaPPsw)[42]
- intravascular administration of a high-affinity humanized anti-PrP antibody to rats prevents the plasticity-disrupting effects induced by exposure to soluble AD brain extracts (Abeta oligomers)[49]
- inhibitor of PTPN5/STEP improves cognitive function in a mouse model with no change in beta amyloid or phospho-tau levels[50]
- scanning ultrasound in conjunction with intravenously administered microbubbles (ultrasound/microbubble therapy) reduced amyloid plaque & improved memory in a mouse model of Alzheimer's disease[51]
- 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (EPPS) rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-beta oligomers & amyloid plaques[53]
- noninvasive, multisensory stimulation in a mouse model of Alzheimer disease helped to clear amyloid & tau & restored at least some cognitive function
- a 40-Hz tone use to entrain firing rate of neurons in the auditory cortex, the hippocampal CA1 region, & the medial prefrontal cortex[61]
- after a week, the tone
- reduced amyloid-beta in the auditory cortex & hippocampal CA1 region
- decreased plaque & phosphorylated tau in CA1 region & auditory cortex
- increased amyloid uptake by microglia
- upregulated astrocytes
- improved spatial & recognition memory (impaired in the experimental mice)
- combining the tone with a 40-Hz light flicker
- augmented entrainment of neuronal activity in all 3 regions
- reduced amyloid plaque throughout the neocortex[61]
- low-dose lithium rescues functional deficits in object recognition, reduces loss of cholinergic boutons in hippocampus, reduces levels of soluble & insoluble cortical Abeta-42, reduces reduces hippocampal Abeta plaque number in McGill-R-Thy1-APP transgenic rats[63]
studies in humans
- HMG CoA reductase inhibitors (statins)[4]
- Alzheimer's Disease Cooperative Study (ADCS)
- Sun Health Research Institute
- atorvastatin may be of some clinical benefit in mild to moderate Alzheimer's disease[21]
- PROSPER
- statins reduce 24-OH cholesterol, but < than reduction in LDL[16]
- also see statins & Alzheimer's disease, statins & the risk of dementia (data NOT supportive)
- non-steroidal anti-inflammatory agents (NSAIDs)
- epidemiologic studies associate NSAID use with diminished risk of AD[5]
- risk may be attenuated with certain NSAIDs, but not others[6][9] (see studies in rodents above)
- direct interaction of certain NSAIDs with gamma-secretase[13][14]
- see in vitro studies above
- no benefit of tarenflurbil (R-flubiprofen), a drug that inhibits gamma-secretase & formation of Abeta42[41]
- no dose information available for NSAIDs that may be of benefit
- vitamins:
- combination of vitamin E & vitamin C may reduce the risk of Alzheimer's disease; RR = 0.22 for users > 5 years[18]
- combination of folate (5 mg), vitamin B6 (25 mg), & vitamin B12 (1 mg) of no benefit[40]
- vitamin B12 without folate or vitamin B6 might be of benefit[44]
- antioxidant combination (vitamin E 800 IU/day, vitamin C 500 mg/day, alpha-lipoic acid (component of pantothenic acid) 900 mg/day, coenzyme Q 400 mg/day[46]
- antioxidant combination associated with greater cognitive decline than placebo (MMSE, -2.8 vs. -0.9 points) & showed a trend toward greater functional deterioration
- no between-group differences or changes in Abeta-42, tau, or phosphorylated tau
- F2-isoprostanes decreased by 19% in the antioxidant combination group[46]
- clioquinol (metal chelator) in phase II clinical trial 3/02
- allegedly withdrawn due to toxicity[7]
- Alzhemed in Phase 3 clinical trials (07/04)
- LY450139 in clinical trials (07/04)
- dimebon in Phase 3 trials (08/08)
- immunization with A-beta(1-42)[22][23]
- associated with meningoencephalitis (6%)[22]
- candidate biomarkers associated with risk of immunotherapy identified from microarray analysis using peripheral blood[22]
- monoclonal antibodies
- 2 monoclonal antibodies against beta-amyloid failed to produce meaningful clinical results[48]
- crenezumab lowers amyloid-beta oligomers in CSF[71]
- aducanumab, a monoclonal Ab that removes beta-amyloid reduces Abeta plaques in Alzheimer's disease[55]
- FDA-approved in 2021
- donanemab targets beta-amyloid (small phase 2 trial)
- lecanemab (BAN2401) also targets beta-amyloid (small phase 2b trial)[77]
- gantenerumab targets A-beta (beta-amyloid)[70]
- reduces amyldoid plaques & lowers CSF total tau & phosphorylated tau
- no evidence of cognitive benefit
- solanezumab targets A-beta[70]
- does not slow cognitive decline in symptomatic patients or show benefit in Alzheimer markers
- semorinemab targets microtubule-associated protein tau
- does not slow progression of Alzheimer's disease[83]
- anti-tau agents not likely to meaningfully slow cognitive impairment[85]
- tau aggregation inhibitors
- tau aggregation inhibitor hydromethylthionine mesylate (HMTM) improves cognition over 18 months in elderly with mild cognitive impairment[88]
- tau aggregation inhibitor (LMTM) of no benefit in patients with mild-to-moderate Alzheimer's disease[56]
- no benefit of intravenous immunoglobulin on cognition or function in patients with AD[57]
- nicotine & its analogs may diminish deposition of Abeta in the entorhinal cortex[26]
- cerebrolysin, a neuropeptide isolated from brain extracts, & its derivative N-PEP-12 may have benefit
- docosahexaenoic acid (omega-3 fatty acid) does not slow decline of mild to moderate AD (2 g/day for 18 months)[43]
- intranasal insulin not effective for AD or MCI[45]
- phase 2A proof-of-concept clinical trial of bexarotene at Cleveland clinic Dec 2013, to treat patients with Alzheimer's disease (BEAT-AD)[5]
- tramiprosate blocks aggregation of beta-amyloid monomers into toxic oligomers
- edonerpic (T-817) of no benefit in patients with mild-to-moderate Alzheimer's disease
- bryostatin (parenteral) tolerated in safety studies may show some cognitive benefits
- 5HT6 receptor antagonist idalopirdine of no benefit alone or added to a cholinesterase inhibitor
- ib drugs
- nilotinib reduces CSF tau
- safe & well-tolerated in patients with Alzheimer's disease
- masitinib
- nilotinib reduces CSF tau
- sumifilam, a compound that binds to filamin improves biomarkers of AD, & may improve episodic memory & spatial working memory[65]
- plasma exchange with albumin replacement may slow symptoms of AD[66]
- plasmapheresis 2.5 to 3 liters of plasma weekly with fresh commercial albumin replacement
- thought to remove amyloid beta bound to albumin from plasma[66]
- sodium benzoate reported to have a 3 point benefit in the 70 point ADAS-Cog score but no change in behavior in women[69]
- hyperbaric oxygen therapy
- 100% oxygen via a mask at twice atmospheric pressure for 90 min session reportedly improved global cognition & memory (although the improvement less than the sum of the standard deviations)[74]
- bumetanide (Bumex) may have benefit in prevention & treatment of apoE4- related Alzheimer's disease[75]
- sildenafil may reduce risk of Alzheimer's disease (RR=0.31)[78]
- SAGE-718 reported to improve Montreal Cognitive Assessment scores (+2.3) within 4 weeks in patients with AD
- drugs with noradrenergic activity used to treat ADHD may show a small positive effect on global cognition in patients with AD & a much larger effect on apathy[84]
- suvorexant acutely decreases tau phosphorylation & amyloid-beta in human CNS[6]
gene transfer studies in humans
- sterotactic injections of adenovirus vector (serotype 2) nerve growth factor (AAV2-NGF) into the nucleus basalis is safe & well-tolerated for 24 months but without affect on clinical outcomes or selected biomarkers (PET scan, MRI)[58]
genomic analysis of the human proteome
- genomic analysis of the proteome from brain, CSF & plasma may identify drug targets for Alzheimer's disease[72]
sensory stimulation
- a device that delivers a combination of auditory & visual stimulations at a frequency of 40 Hertz (Hz) elicits gamma oscillation in the brain as recorded by EEG
transcranial electromagnetic stimulation
- in-home bioengineered head device emitting electromagnetic waves worn for two 1-hour periods each day
- allegedly reverses memory impairment in AD after 2 months[62]
- 4+ point improvement in ADAS-cog score (70 point scale)
- MRI evidence of changes in the cingulate cortex
- CSF-tau & CSF-A-beta apparently changed
- induces brain mitochondrial enhancement
- none of the 8 patients wanted to return their head device[62]
- allegedly reverses memory impairment in AD after 2 months[62]
- a specially designed helmet delivering near-infrared light to the brain may improve memory, motor function, & processing skills in cognitively intact healthy older adults[81]
- 24 weeks of precuneus repetitive transcranial magnetic stimulation may slow down cognitive and functional decline in Alzheimer's disease[86]
low-intensity focused ultrasound
- MRI-guided low-intensity focused ultrasound with injected microbubbles to temporarily open the blood-brain barrier reduces beta-amyloid plaques & cognitive impairment in patients with mild Alzheimer's disease[73]
- ability to transiently open the blood-brain barrier on demand safely facilitates new therapeutic strategies for treating brain disease
- patients wear a helmet that has ultrasound probes
- MRI is used to visualize areas of the brain with amyloid plaques.
- ultrasound waves travel through the scalp & skull converging on the locations in the brain targeted with MRI with a high degree of plaques
- tiny spherical microbubbles injected into the bloodstream oscillate in areas targeted with ultrasound, resulting in a transient opening of the blood-brain barrier
- treatment takes ~2 hours
- patients undergo 3 treatments, each 2 weeks apart.
plasma exchange
- plasma exchange with albumin replacement in patients with mild Alzheimer's disease showed improvement in memory, language abilities, processing speed, & quality of life[76]
other agents
- etanercept a recombinant protein that inhibits TNF-alpha of no benefit[52]
- rationale: elevated TNF in CSF of patients with AD
- issue of blood-brain barrier (etanercept given SC) not addressed[52]
- BACE1 inhibitor verubecestat does not reduce cognitive or functional decline in patients with mild-moderate AD[59]
- sargramostim (GM-CSF) shows potential in small phase II trial[68]
- cilostazol may help to preserve general cognitive function, including preservation in category fluency[87]
herbal therapy
- Huperzine A (Chinese traditional herb)
- contains cholinesterase inhibitor(s) {not FDA approved, no published studies}[8]
gum disease
- Porphyromonas gingivalis is suggested as a potential pathogen of AD[80]
in silico
- machine learning to evaluate gene involvement in AD pathology produced a list of 15 FDA-approved drugs that might be repurposed to treat Alzheimer's disease; 5 are Janus kinase inhibitors[67]
More general terms
Additional terms
- Alzheimer's disease (ADD)
- guidelines for Alzheimer's disease management
- prevention of Alzheimer's disease/dementia
References
- ↑ 1.0 1.1 Journal Watch 19:128, 1999 Schenk D et al Immunization with amyloid-beta attenuates Alzheimer-disease- like pathology in the PDAPP mouse. Nature 400:173, 1999 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10408445
- ↑ 2.0 2.1 Journal Watch 20:147, 2000 Cannon BF et al Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature Med 6:916, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10932230
- ↑ 3.0 3.1 Chen G et al A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease. Nature 408:975, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11140684
Pearson JC et al A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 408:979, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11140685
Morgan D A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408:982, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11140686 - ↑ 4.0 4.1 Marx J. Alzheimer's disease. Bad for the heart, bad for the mind? Science 294:508, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11641483
- ↑ 5.0 5.1 5.2 Journal Watch 21(24):193, 2001 in 't Veld et al Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. NEJM 345:1515,2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11794217
- ↑ 6.0 6.1 6.2 6.3 Journal Watch 21(24):194, 2001 Weggen S et al A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 414:212, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11700559
- ↑ 7.0 7.1 7.2 7.3 Cole G., GRECC, VA Medical Center, Sepulveda, (unpublished)
Calon F, Lim GP, Morihara T, Yang F, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease. Eur J Neurosci. 2005 Aug;22(3):617-26. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/16101743 - ↑ 8.0 8.1 <Internet> http://www.alz.org
- ↑ 9.0 9.1 9.2 9.3 Journal Watch 23(14):109, 2003
Alsen PS et al Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 289:2819, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12783912
Launer IJ Nonsteroidal anti-inflammatory drugs and Alzheimer disease: what's next? JAMA 289:2865, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12783919 - ↑ 10.0 10.1 Journal Watch 23(18):145, 2003 Etminan M et al Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. BMJ 327:128, 2003 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/12869452 <Internet> http://bmj.com/cgi/content/full/327/7407/128
- ↑ 11.0 11.1 Rees T, Hammond PI, Soreq H, Younkin S, Brimijoin S. Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex. Neurobiol Aging. Oct;24(6):777-87. 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12927760
- ↑ 12.0 12.1 Permanne B et al Reduction of amyloid load and cerebral damage in a transgenic mouse model of Alzheimer's disease by treatment with a beta-sheet breaker peptide. FASEB J. 2002 Jun;16(8):860-2. Epub 2002 Apr 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11967228
- ↑ 13.0 13.1 13.2 13.3 Weggen S et al, Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity. J Biol Chem. 2003 Aug 22;278(34):31831-7. Epub 2003 Jun 12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12805356
- ↑ 14.0 14.1 14.2 14.3 Eriksen JL et al, NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J Clin Invest. 2003 Aug;112(3):440-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12897211
- ↑ Takahashi Y et al, Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation. J Biol Chem. 2003 May 16;278(20):18664-70. Epub 2003 Mar 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12637581
- ↑ 16.0 16.1 Vega GL et al Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol. 2003 Apr;60(4):510-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12707064
- ↑ 17.0 17.1 Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5856-61. Epub 2001 Apr 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11296263
Hoglund K, Wiklund O, Vanderstichele H, Eikenberg O, Vanmechelen E, Blennow K. Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins. Arch Neurol. 2004 Mar;61(3):333-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15023808 - ↑ 18.0 18.1 Zandi PP et al, Arch Neurol 6:18, 2004 http://archneur.ama-assn.org/cgi/content/abstract/61/1/82
- ↑ 19.0 19.1 Journal Watch 24(24):184, 2004 Gestwicki JE, Crabtree GR, Graef IA. Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation. Science. 2004 Oct 29;306(5697):865-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15514157
- ↑ 20.0 20.1 Journal Watch 24(24):184, 2004 Hutter-Paier B, Huttunen HJ, Puglielli L, Eckman CB, Kim DY, Hofmeister A, Moir RD, Domnitz SB, Frosch MP, Windisch M, Kovacs DM. The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease. Neuron. 2004 Oct 14;44(2):227-38. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15473963
- ↑ 21.0 21.1 Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Browne P, Wasser D, Johnson-Traver S, Lochhead J, Ziolwolski C. Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch Neurol. 2005 May;62(5):753-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15883262
- ↑ 22.0 22.1 22.2 22.3 O'Toole M et al Risk factors associated with beta-amyloid(1-42) immunotherapy in preimmunization gene expression patterns of blood cells Arch of Neurol 62:1513, 2005
- ↑ 23.0 23.1 McGeer EG, McGeer PL. Abeta immunotherapy and other means to remove amyloid. Curr Drug Targets CNS Neurol Disord. 2005 Oct;4(5):569-73. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16266289
- ↑ 24.0 24.1 Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. J Biol Chem. 2005 Nov 11;280(45):37377-82. Epub 2005 Sep 14. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16162502
- ↑ 25.0 25.1 Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest. 2005 Oct;115(10):2774-83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16151530
- ↑ 26.0 26.1 Court JA, Johnson M, Religa D, Keverne J, Kalaria R, Jaros E, McKeith IG, Perry R, Naslund J, Perry EK. Attenuation of Abeta deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking. Neuropathol Appl Neurobiol. 2005 Oct;31(5):522-35. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16150123
- ↑ 27.0 27.1 Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta- induced cognitive deficits and neuropathology. Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11755008
Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001 Nov 1;21(21):8370-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11606625 - ↑ 28.0 28.1 Jankowsky JL et al, Persistent amyloidosis following suppression of Abeta production in a transgenic modell of Alzheimer disease PLoS Med 2005; Dec, 2:e355 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16279840
- ↑ 29.0 29.1 McLaurin J, Kierstead ME, Brown ME, Hawkes CA, Lambermon MH, Phinney AL, Darabie AA, Cousins JE, French JE, Lan MF, Chen F, Wong SS, Mount HT, Fraser PE, Westaway D, George-Hyslop PS. Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse Alzheimer phenotype in a mouse model. Nat Med. 2006 Jul;12(7):801-8. Epub 2006 Jun 11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16767098
- ↑ 30.0 30.1 30.2 Caccamo A et al, M1 receptors play a central role in modulating AD-like pathology in transgenic mice Neuron 2006, 49:671 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16504943
- ↑ 31.0 31.1 31.2 ADAP Research Group, Lykestos CG et al Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology 2007, 68:1800 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17460158
- ↑ 32.0 32.1 Hartman RE, Shah A, Fagan AM, Schwetye KE, Parsadanian M, Schulman RN, Finn MB, Holtzman DM. Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease. Neurobiol Dis. 2006 Dec;24(3):506-15. Epub 2006 Sep 28. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17010630
- ↑ 33.0 33.1 Wang J, Ho L, Zhao Z, Seror I, Humala N, Dickstein DL, Thiyagarajan M, Percival SS, Talcott ST, Pasinetti GM. Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease. FASEB J. 2006 Nov;20(13):2313-20. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17077308
- ↑ 34.0 34.1 Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers JT, Puigserver P, Sadoshima J, Deng H, Pedrini S, Gandy S, Sauve AA, Pasinetti GM. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem. 2006 Aug 4;281(31):21745-54. Epub 2006 Jun 2. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16751189
- ↑ 35.0 35.1 Sagare A et al, Clearance of amyloid-beta by circulating lipoprotein receptors Nat Med 2007, 13:1029 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17694066
- ↑ 36.0 36.1 Wang J et al Valsartan lowers brain b-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease Journal of Clinical Investigation http://www.jci.org http://www.pubmedcentral.nih.gov/picrender.fcgi?doi=10.1172/JCI31547&blobtype=pdf PMID: https://www.ncbi.nlm.nih.gov/pubmed/17965777
- ↑ 37.0 37.1 Wang J, Ho L, Qin W, Rocher AB, Seror I, Humala N, Maniar K, Dolios G, Wang R, Hof PR, Pasinetti GM. Caloric restriction attenuates beta-amyloid neuropathology in a mouse model of Alzheimer's disease. FASEB J. 2005 Apr;19(6):659-61. Epub 2005 Jan 13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15650008
- ↑ 38.0 38.1 Rajendran L et al, Efficient inhibition of the Alzheimer's disease beta-secretase by membrane targeting. Science 2008, 320:520 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18436784
- ↑ 39.0 39.1 39.2 39.3 Vlad SC et al. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 2008 May 6; 70:1672 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18458226
- ↑ 40.0 40.1 Aisen PS et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial. JAMA 2008 Oct 15; 300:1774. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18854539
Clarke RJ and Bennett DA. B vitamins for prevention of cognitive decline: Insufficient evidence to justify treatment. JAMA 2008 Oct 15; 300:1819. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18854547 - ↑ 41.0 41.1 Green RC et al. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: A randomized controlled trial. JAMA 2009 Dec 16; 302:2557. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20009055
Montine TJ and Larson EB. Late-life dementias: Does this unyielding global challenge require a broader view? JAMA 2009 Dec 16; 302:2593. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20009062 - ↑ 42.0 42.1 Arendasha GW et al Electromagnetic Field Treatment Protects Against and Reverses Cognitive Impairment in Alzheimer's Disease Mice Journal of Alzheimer's Disease (preprint Jan 2010) http://iospress.metapress.com/content/d6r1371722422hg2/fulltext.pdf DOI:http://dx.doi.org/ 10.3233/JAD-2009-1228
- ↑ 43.0 43.1 Quinn JF et al Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease JAMA. 2010;304(17):1903-1911 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21045096 <Internet> http://jama.ama-assn.org/cgi/content/full/304/17/1903
- ↑ 44.0 44.1 Hooshmand B et al Homocysteine and holotranscobalamin and the risk of Alzheimer disease: A longitudinal study. Neurology 2010 Oct 19; 75:1408. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20956786
- ↑ 45.0 45.1 Craft S et al Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment Arch Neurol. Published online September 12, 2011 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21911655 <Internet> http://archneur.ama-assn.org/cgi/content/full/archneurol.2011.233
Craft S et al. Safety, efficacy, and feasibility of intranasal insulin for the treatment of mild cognitive impairment and Alzheimer disease dementia: A randomized clinical trial. JAMA Neurol 2020 Jun 22; PMID: https://www.ncbi.nlm.nih.gov/pubmed/32568367 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2767376 - ↑ 46.0 46.1 46.2 Galasko DR et al. Antioxidants for Alzheimer disease: A randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 2012 Mar 19 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22431837 <Internet> http://archneur.ama-assn.org/cgi/content/abstract/archneurol.2012.85v1
- ↑ Cummings JL and Zhong K Beraxotene for Alzheimer's disease: Innovative Clinical Trial Could Open the Door to Disease-Modifying Therapy. Cleveland Clinic: Neurosciences Pathways. CLEVELANDCLINIC.ORG/NEUROSCIENCE
- ↑ 48.0 48.1 Salloway S et al Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease. N Engl J Med 2014; 370:322-333. January 23, 2014 http://www.nejm.org/doi/full/10.1056/NEJMoa1304839 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24450891
Doody RS et al Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease. N Engl J Med 2014; 370:311-321. January 23, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/4450890 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1312889
Honig LS, Vellas B, Woodward M et al Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease. N Engl J Med 2018; 378:321-330. Jan 25, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29365294 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1705971 - ↑ 49.0 49.1 Klyubin I et al. Peripheral administration of a humanized anti-PrP antibody blocks Alzheimer's disease Abeta synaptotoxicity. J Neurosci 2014 Apr 30; 34:6140 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/2479018 <Internet> http://www.jneurosci.org/content/34/18/6140
- ↑ 50.0 50.1 Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, et al. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease. PLoS Biol (2014) 12(8): e1001923 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25093460 <Internet> http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001923
- ↑ 51.0 51.1 Leinenga G, Gotz J Scanning ultrasound removes amyloid-beta and restores memory in an Alzheimer's disease mouse model. Sci Transl Med 11 March 2015: Vol. 7, Issue 278, p. 278ra33 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25761889 <Internet> http://stm.sciencemag.org/content/7/278/278ra33
- ↑ 52.0 52.1 52.2 Torro J Is Etanercept Safe and Well Tolerated in Alzheimer Disease? NEJM Journal Watch. May 27, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
Butchart J et al. Etanercept in Alzheimer disease: A randomized, placebo- controlled, double-blind, phase 2 trial. Neurology 2015 May 26; 84:2161 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25934853 <Internet> http://www.neurology.org/content/84/21/2161 - ↑ 53.0 53.1 Kim HY, Kim HV, Jo S et al EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-beta oligomers and plaques. Nature Communications 6, Article number: 8997 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26646366 <Internet> http://www.nature.com/ncomms/2015/151208/ncomms9997/abs/ncomms9997.html
- ↑ 54.0 54.1 EurekAlert. Oct 24, 2016 Phase 3 analyses in Alzheimer's show clinical benefit of tramiprosate in APOE4 carriers https://www.eurekalert.org/pub_releases/2016-10/tyn-p3102416.php
- ↑ 55.0 55.1 Sevigny J, Chiao P, Bussiere T et al The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature. 2016 Aug 31;537(7618):50-6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27582220
Reiman EM Alzheimer's disease: Attack on amyloid-beta protein. Nature. 2016 Aug 31;537(7618):36-7. doi:http://dx.doi.org/ 10.1038/537036a. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27582214 - ↑ 56.0 56.1 Gauthier S et al. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: A randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 2016 Nov 15; 388:2873. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27863809 Free PMC Article
Rafii MS. Targeting tau protein in Alzheimer's disease. Lancet 2016 Nov 15; 388:2842 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27863808 - ↑ 57.0 57.1 Relkin NR, Thomas RG, Rissman RA et al. A phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology 2017 Apr 5 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28381506 <Internet> http://www.neurology.org/content/88/18/1768
- ↑ 58.0 58.1 58.2 George J. No Cognitive Benefit in Alzheimer's Gene Transfer Trial. AAV2-NGF injections give same results as sham treatment. MedPage Today. March 26, 2018 https://www.medpagetoday.com/neurology/alzheimersdisease/71992
Rafii MS, Tuszynski MH, Thomas RG, et al Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease. A Randomized Clinical Trial. JAMA Neurol. Published online March 26, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29582053 https://jamanetwork.com/journals/jamaneurology/article-abstract/2675302
Honig LS Gene Therapy in Alzheimer Disease - It May Be Feasible, But Will It Be Beneficial? JAMA Neurol. Published online March 26, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29582049 https://jamanetwork.com/journals/jamaneurology/article-abstract/2675299 - ↑ 59.0 59.1 Egan MF, Kost J, Tariot PN et al Randomized Trial of Verubecestat for Mild-Moderate Alzheimer's Disease. N Engl J Med 2018; 378:1691-1703. May 3, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29719179 https://www.nejm.org/doi/full/10.1056/NEJMoa1706441
- ↑ 60.0 60.1 Biogen Inc. Phase II clinical trial (Study 201) of BAN2401 Alzheimer's Association International Conference 2018
- ↑ 61.0 61.1 61.2 Martorell AJ, Paulson AL, Suk HJ et al. Multi-sensory gamma stimulation ameliorates Alzheimer's-associated pathology and improves cognition. Cell 2019 Apr 4; 177:256. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30879788 https://www.cell.com/cell/fulltext/S0092-8674(19)30163-1
- ↑ 62.0 62.1 62.2 EurekAlert News Release Sept 17, 2019 Alzheimer's memory loss reversed by new head device using electromagnetic waves. https://eurekalert.org/pub_releases/2019-09/ip-am091719.php
Arendash G Cao C, Abulaban H et al A Clinical Trial of Transcranial Electromagnetic Treatment in Alzheimer's Disease: Cognitive Enhancement and Associated Changes in Cerebrospinal Fluid, Blood, and Brain Imaging. Journal of Alzheimer's Disease, 71(1):57-82, 2019 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad190367 - ↑ 63.0 63.1 Wilson EN, Do Carmo S, Welikovitch LA et al NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats. Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 723-739, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31868669 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad190862
- ↑ George J Alzheimer's Markers Altered With Cancer Drug -Early nilotinib study suggests it has potential to be a disease-modifying drug. MedPage Today May 29, 2020 https://www.medpagetoday.com/neurology/alzheimersdisease/86770
Nackerdien Z Cancer Drug Nilotinib Changes Alzheimer's Disease Biomarkers - his may be a first step towards a disease-modifying treatment, phase II study suggests. MedPage Today 2020-06-18 https://www.medpagetoday.org/neurology/alzheimersdisease/87151
Turner RS, Hebron ML, Lawler A et al Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease. Ann Neurol 2020. May 28 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32468646 https://onlinelibrary.wiley.com/doi/full/10.1002/ana.25775 - ↑ 65.0 65.1 Cassava Sciences. Sept 14, 2020 Cassava Sciences Announces Final Results of a Phase 2b Clinical Study of Sumifilam in Patients with Alzheimer's Disease. https://www.globenewswire.com/news-release/2020/09/14/2092861/0/en/Cassava-Sciences-Announces-Final-Results-of-a-Phase-2b-Clinical-Study-of-Sumifilam-in-Patients-with-Alzheimer-s-Disease.html
- ↑ 66.0 66.1 66.2 Anderson P Plasma Exchange 'Encouraging' as Novel Alzheimer's Treatment Medscape - Jul 31, 2020. https://www.medscape.com/viewarticle/934937
- ↑ 67.0 67.1 Rodriguez S, Hug C, Todorov P et al Machine learning identifies candidates for drug repurposing in Alzheimer's disease. Nat Commun 12, 1033 (2021) PMID: https://www.ncbi.nlm.nih.gov/pubmed/33589615 PMCID: PMC7884393 Free PMC article https://www.nature.com/articles/s41467-021-21330-0
- ↑ 68.0 68.1 George J Marrow Cell Stimulator to Treat Alzheimer's s Disease?
Unusual approach pans out in mid-stage trial. MedPage Today March 24, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/91795
Potter H et al Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer's disease. Alzheimer's & Dementia. 2021. March 24. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33778150 PMCID: PMC7988877 Free PMC article https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12158 - ↑ 69.0 69.1 69.2 Monaco K Could a Food Preservative Slow Cognitive Decline in Dementia Patients?
Post hoc data of negative trial suggested women may see benefit from sodium benzoate. MedPage Today April 21, 2021 https://www.medpagetoday.com/psychiatry/dementia/92197
Lin CH, Chen PK, Wang SH, Lane HY Effect of sodium benzoate on cognitive function among patients with behavioral and psychological symptoms of dementia. JAMA Netw Open. 2021;4(4):e216156 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33881530 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779038 - ↑ 70.0 70.1 70.2 George J Investigational Alzheimer's Drug Shows Effects in Inherited Early-Onset Disease MedPage Today June 21,2021 https://www.medpagetoday.com/neurology/alzheimersdisease/93193
Salloway S. et al. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease Nature Medicine (2021) PMID: https://www.ncbi.nlm.nih.gov/pubmed/34155411 https://www.nature.com/articles/s41591-021-01369-8 - ↑ 71.0 71.1 Yang T, Dang Y, Ostaszewski B, Mengel D et al Target engagement in an alzheimer trial: Crenezumab lowers amyloid beta oligomers in cerebrospinal fluid Ann Neurol. 2019 Aug;86(2):215-224 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31168802 Free PMC article Clinical Trial.
- ↑ 72.0 72.1 Yang C, Farias FHG, Ibanez L et al Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders. Nat Neurosci 2021. July 8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34239129 https://www.nature.com/articles/s41593-021-00886-6
- ↑ 73.0 73.1 Anderson P Low-Intensity Focused Ultrasound Safe, Effective in Mild Alzheimer's Disease. Medscape. August 30, 2021 https://www.medscape.com/viewarticle/957487
- ↑ 74.0 74.1 Shapira R, Efrati S, Ashery U. Hyperbaric oxygen therapy as a new treatment approach for Alzheimer's disease. Neural Regen Res. 2018 May;13(5):817-818. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29863011 Free PMC article. No abstract available.
Shapira R, Gdalyahu A, Gottfried I et al Hyperbaric oxygen therapy alleviates vascular dysfunction and amyloid burden in an Alzheimer's disease mouse model and in elderly patients. Aging (Albany NY). 2021 Sep 9;13(17):20935-20961. Epub 2021 Sep 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34499614 Free PMC article. - ↑ 75.0 75.1 Li Z, Zhao N A water pill against Alzheimer's disease. Nat Aging 2021. 1, 868-869 News & Views https://www.nature.com/articles/s43587-021-00124-5
Taubes A, Nova P, Zalocusky KA et al Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4-related Alzheimer's disease. Nat Aging 2021. 1, 932-947 Not indexed in PubMed https://www.nature.com/articles/s43587-021-00122-7 - ↑ 76.0 76.1 Boada M, Lopez OL, Olazaran J et al Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study. Alzheimer's & Dementia. 2021. Nov 2 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34726348 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12477
- ↑ 77.0 77.1 Anderson P Lecanemab Effective in Clearing Amyloid in Early Alzheimer's. Medscape. November 23, 2021 https://www.medscape.com/viewarticle/963516
- ↑ 78.0 78.1 George J Can Viagra Prevent Alzheimer's? Sildenafil shows potential for drug repurposing MedPage Today December 6, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/96018
Fang J, Zhang P, Zhou Y et al Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease. Nat Aging (2021) Not indexed in PubMed https://www.nature.com/articles/s43587-021-00138-z - ↑ 79.0 79.1 Anderson P Sensory Stimulation Promising for Alzheimer's Disease. Medscape. November 15, 2021 https://www.medscape.com/viewarticle/963003
- ↑ 80.0 80.1 Anderson P Gum Disease Bacteria a New Treatment Target for Alzheimer's? Medscape. November 23, 2021 https://www.medscape.com/viewarticle/963574
- ↑ 81.0 81.1 Brooks M Novel Light Therapy Helmet Boosts Brain Function. Medscape. October 21, 2021 https://www.medscape.com/viewarticle/961326
- ↑ Whitlock Burton K Experimental Drug May Boost Executive Function in Alzheimer's Medscape. March 31, 2022 https://www.medscape.com/viewarticle/971365
- ↑ 83.0 83.1 Teng E, Manser PT, Pickhorn K et al Safety and Efficacy of Semorinemab in Individuals With Prodromal to Mild Alzheimer Disease. A Randomized Clinical Trial. JAMA Neurol. Published online June 13, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35696185 https://jamanetwork.com/journals/jamaneurology/fullarticle/2793069
- ↑ 84.0 84.1 Geroge J ADHD Drugs May Treat Alzheimer's Cognitive Symptoms Effectively. Positive effect on global cognition, apathy in meta-analysis. MedPage Today July 5, 2022 https://www.medpagetoday.com/neurology/alzheimersdisease/99583
David MCB, Del Giovane M, Liu KY et al Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer's disease: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2022. July 5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35790417 https://jnnp.bmj.com/content/early/2022/05/31/jnnp-2022-329136 - ↑ 85.0 85.1 Zheng X, Tang Y, Yang Q et al Effectiveness and safety of anti-tau drugs for Alzheimer's disease: Systematic review and meta-analysis. J Am Geriatr Soc 2022. Oct 8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36208415 Review. https://agsjournals.onlinelibrary.wiley.com/doi/abs/10.1111/jgs.18025
- ↑ 86.0 86.1 Koch G, Casula EP, Bonni S et al Precuneus magnetic stimulation for Alzheimer's disease: a randomized, sham-controlled trial. Brain. 2022. Oct 25 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36281767 https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awac285/6701823
- ↑ 87.0 87.1 Chien CG, Huang LC, Li KY, Yang YH. Cognitive effects of cilostazol in Alzheimer's dementia patients with peripheral arterial occlusive disease: A case-control study. Geriatrics Gerontology International. 2023. Jan 23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36682741 https://onlinelibrary.wiley.com/doi/abs/10.1111/ggi.14542
- ↑ 88.0 88.1 Brooks M Oral Tau Inhibitor Continues to Show Promise in Alzheimer's Medscape. July 21, 2023 https://www.medscape.com/viewarticle/994646
- ↑ Lucey BP, Liu H, Toedebusch CD et al Suvorexant Acutely Decreases Tau Phosphorylation and Abeta in the Human CNS. Ann Neurol. 2023 Jul;94(1):27-40 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36897120 PMCID: PMC10330114 (available on 2024-07-01)