Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial

Journal of Alzheimer's Disease

Volumn 57, Issue 4, 2017, Pages 1325-1334

  Craft, Suzanne ^a   Claxton, Amy ^b   Baker, Laura D ^a   Hanson, Angela J ^c   Cholerton, Brenna ^d   Trittschuh, Emily H ^c,e   Dahl, Deborah ^a   Caulder, Erin ^a   Neth, Bryan ^a   Montine, Thomas J ^d   Jung, Youngkyoo ^a   Maldjian, Joseph ^f   Whitlow, Christopher ^a   Friedman, Seth ^g   De La Monte, Suzanne ^a  

^a WAKE FOREST SCHOOL OF MEDICINE   (United States)

^b ALKERMES INC   (United States)

^c UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^d STANFORD UNIVERSITY   (United States)

^e VA PUGET SOUND HEALTH CARE SYSTEM   (United States)

^f UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^g SEATTLE CHILDREN S HOSPITAL   (United States)

Author keywords

Alzheimer's disease; clinical trial; insulin; intranasal; magnetic resonance imaging; memory

Indexed keywords

BIOLOGICAL MARKER; INSULIN DETEMIR; PIG INSULIN; PLACEBO; AMYLOID BETA PROTEIN; AMYLOID BETA-PROTEIN (1-42); INSULIN DERIVATIVE; MAPT PROTEIN, HUMAN; NOOTROPIC AGENT; PEPTIDE FRAGMENT; TAU PROTEIN;

AGED; ALZHEIMER DISEASE; ALZHEIMER DISEASE ASSESSMENT SCALE; ARTICLE; CLINICAL ARTICLE; COGNITION; CONTROLLED STUDY; DAILY LIFE ACTIVITY; DEMENTIA ASSESSMENT; DEMENTIA SEVERITY RATING SCALE; DOUBLE BLIND PROCEDURE; DRUG DELIVERY DEVICE; DRUG SAFETY; FEMALE; HUMAN; INSULIN TREATMENT; INTENTION TO TREAT ANALYSIS; LUMBAR PUNCTURE; MALE; MEDICATION COMPLIANCE; MILD COGNITIVE IMPAIRMENT; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SCANNER; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RATING SCALE; RESPIRATORY TRACT DISEASE; RHINITIS; UNSPECIFIED SIDE EFFECT; BRAIN; CEREBROSPINAL FLUID; COMPARATIVE STUDY; DIAGNOSTIC IMAGING; DRUG EFFECTS; ORGAN SIZE; PSYCHOLOGY; TREATMENT OUTCOME;

ACTIVITIES OF DAILY LIVING; AGED; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; BIOMARKERS; BRAIN; COGNITION; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INSULINS; MAGNETIC RESONANCE IMAGING; MALE; NOOTROPIC AGENTS; ORGAN SIZE; PEPTIDE FRAGMENTS; TAU PROTEINS; TREATMENT OUTCOME;

EID: 85018745780     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-161256     Document Type: Article

References (31)

1. Ribe EM, Lovestone S (2016) Insulin signalling in Alzheimer's disease and diabetes: From epidemiology to molecular links. J Intern Med 280, 430-442.
2. Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, Greengard P, Xu H (2001) Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci 21, 2561-2570.
3. Lee CC, Kuo YM, Huang CC, Hsu KS (2009) Insulin rescues amyloid beta-induced impairment of hippocampal long-term potentiation. Neurobiol Aging 30, 377-387.
4. De Felice FG, Vieira MN, Bomfim TR, Decker H, Velasco PT, Lambert MP, Viola KL, Zhao WQ, Ferreira ST, Klein WL (2009) Protection of synapses against Alzheimer'slinked toxins: Insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A 106, 1971-1976.
5. Yarchoan M, Toledo JB, Lee EB, Arvanitakis Z, Kazi H, Han LY, Louneva N, Lee VM, Kim SF, Trojanowski JQ, Arnold SE (2014) Abnormal serine phosphorylation of insulin receptor substrate 1 is associated with tau pathology in Alzheimer's disease and tauopathies. Acta Neuropathol 128, 679-689.
6. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr (1998) Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: Relationship to severity of dementia and apolipoprotein E genotype. Neurology 50, 164-168.
7. Lochhead JJ,Wolak DJ, PizzoME,ThorneRG(2015) Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration. J Cereb Blood Flow Metab 35, 371-381.
8. Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL (2002) Sniffing neuropeptides: A transnasal approach to the human brain. Nat Neurosci 5, 514-516.
9. Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C, Craft S (2015) Long acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J Alzheimers Dis 45, 1269-1270.
10. Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B (2012) Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: A pilot clinical trial. Arch Neurol 69, 29-38.
11. Claxton A, Baker LD,WilkinsonCW, Trittschuh EH, Chapman D,Watson GS, Cholerton B, Plymate SR, Arbuckle M, Craft S (2013) Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer's disease. J Alzheimers Dis 35, 789-797.
12. Kurtzhals P (2004) Engineering predictability and protraction in a basal insulin analogue: The pharmacology of insulin detemir. Int J Obes Relat Metab Disord 28(Suppl 2), S23-S28.
13. De Leeuw I,Vague P, Selam JL, Skeie S, Lang H, Draeger E, Elte JW (2005) Insulin detemir used in basal-bolus therapy in people with type 1 diabetes is associated with a lower risk of nocturnal hypoglycaemia and less weight gain over 12 months in comparison to NPH insulin. Diabetes Obes Metab 7, 73-82.
14. Tschritter O, Hennige AM, Preissl H, Porubska K, Schafer SA, Lutzenberger W, Machicao F, Birbaumer N, Fritsche A, Haring HU (2007) Cerebrocortical beta activity in overweight humans responds to insulin detemir. PLoS One 2, e1196.
15. Roberts RO, Geda YE, Knopman DS, Cha RH, Pankratz VS, Boeve BF, Ivnik RJ, Tangalos EG, Petersen RC, Rocca WA (2008) The Mayo Clinic Study of Aging: Design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology 30, 58-69.
16. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34, 939-944.
17. JiangY, LiY, LiuX(2015) Intranasal delivery: Circumventing the iron curtain to treat neurological disorders. Expert Opin Drug Deliv 12, 1717-1725.
18. Kumar NN, Gautam M, Lochhead JJ, Wolak DJ, Ithapu V, Singh V, Thorne RG (2016) Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: Implications for nasal physiology and drug delivery. Sci Rep 6, 31732.
19. Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, DeGroodt W, Mehta P, Craft S (2008) Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 70, 440-448.
20. Coen R, Kinsella A, Lambe R, KennyM, Darragh A (1990) Creating equivalent word lists for the Buschke Selective Reminding Test. Hum Psychopharmacol 5, 47-51.
21. Rosen WG, Mohs RC, Davis KL (1984) A new rating scale for Alzheimer's disease. Am J Psychiatry 141, 1356-1364.
22. Clark CM, EwbankDC(1996) Performance of the dementia severity rating scale: A caregiver questionnaire for rating severity in Alzheimer disease. Alzheimer Dis Assoc Disord 10, 31-39.
23. Maldjian JA, Baer AH, Kraft RA, Laurienti PJ, Burdette JH (2009) Fully automated processing of fMRI data in SPM: From MRI scanner to PACS. Neuroinformatics 7, 57-72.
24. Ashburner J, Friston KJ (2000) Voxel-based morphometry - the methods. Neuroimage 11, 805-821.
25. Wang WY, Yu JT, Liu Y, Yin RH, Wang HF, Wang J, Tan L, Radua J, Tan L (2015) Voxel-based meta-analysis of grey matter changes in Alzheimer's disease. Transl Neurodegener 4, 6.
26. Harari O, Cruchaga C, Kauwe JS, Ainscough BJ, Bales K, Pickering EH, Bertelsen S, Fagan AM, Holtzman DM, Morris JC, Goate AM, Alzheimer's Disease Neuroimaging Initiative (2014) Phosphorylated tau-Abeta42 ratio as a continuous trait for biomarker discovery for early-stage Alzheimer's disease in multiplex immunoassay panels of cerebrospinal fluid. Biol Psychiatry 75, 723-731.
27. Sciacca L, Cassarino MF, Genua M, Pandini G, Le Moli R, Squatrito S, Vigneri R (2010) Insulin analogues differently activate insulin receptor isoforms and post-receptor signalling. Diabetologia 53, 1743-1753.
28. Kurtzhals P (2007) Pharmacology of insulin detemir. Endocrinol Metab Clin North Am 36(Suppl 1), 14-20.
29. Stanyon HF, Viles JH (2012) Human serum albumin can regulate amyloid-beta peptide fiber growth in the brain interstitium: Implications for Alzheimer disease. J Biol Chem 287, 28163-28168.
30. Maimaiti S, Anderson KL, DeMoll C, Brewer LD, Rauh BA, Gant JC, Blalock EM, Porter NM, Thibault O (2016) Intranasal insulin improves age-related cognitive deficits and reverses electrophysiological correlates of brain aging. J Gerontol A Biol Sci Med Sci 71, 30-39.
31. Benedict C, Hallschmid M, Schmitz K, Schultes B, Ratter F, Fehm HL, Born J, Kern W (2007) Intranasal insulin improves memory in humans: Superiority of insulin aspart. Neuropsychopharmacology 32, 239-243.