title: A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer's disease.
abstract: Poor vitamin D nutrition is linked with dementia, but vitamin D has not been tested in a randomized controlled trial (RCT) in Alzheimer's disease (AD). Nasal insulin acutely improves cognition and vitamin D upregulates insulin receptor expression and enhances insulin action. In an RCT we examined the effect of high-dose vitamin D followed by nasal insulin on memory and disability in mild-moderate AD. 63 community-dwelling individuals aged > 60 were recruited; 32 with mild-moderate disease (Folstein Mini-Mental State Examination [MMSE] score 12-24) met entry criteria and were randomized. All took low-dose vitamin D (1000 IU/day) throughout. After run-in (8 weeks), they were randomized to additional high-dose D/placebo for 8 weeks, followed immediately by randomization to nasal insulin (60 IU qid)/placebo for 48 h. Primary outcome measures were Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and Disability Assessment in Dementia (after high-dose D) and ADAS-cog and Wechsler Memory Scale-Revised Logical memory (WMS-R LM) for immediate and delayed recall (after nasal insulin). Baseline median (interquartile range, IR) age, MMSE, and ADAS-cog were 77.5 (69-80), 19.5 (17-22), and 25.5 (20-31), respectively. Median 25OHD increased from 49 to 60 nM (p < 0.01) after run-in and was 187 nM after high-dose vitamin D and 72 nM after placebo (p < 0.001). Neither cognition nor disability changed significantly after high-dose D. ADAS-cog improved by a median (IR) of 9 (1-11) with nasal insulin after placebo high-dose vitamin D (p = 0.02), but may represent regression to the mean as WLS-R LM did not change. We conclude that high-dose vitamin D provides no benefit for cognition or disability over low-dose vitamin D in mild-moderate AD.
authors.affiliation: Royal Melbourne Hospital, Parkville, VIC, Australia Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. mark.stein@mh.org.au
authors.forename: Mark S
authors.initials: MS
authors.lastname: Stein
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Scherer
authors.forename: Kylie S
authors.initials: KS
authors.lastname: Ladd
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
mesh_terms: D000281:Administration, Intranasal; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D003071:Cognition / Q000187:drug effects; D003863:Depression / Q000209:etiology / Q000523:psychology; D019587:Dietary Supplements; D004311:Double-Blind Method; D004872:Ergocalciferols / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010865:Pilot Projects; D016896:Treatment Outcome; D014808:Vitamin D Deficiency / Q000150:complications; D014815:Vitamins / Q000627:therapeutic use*; D014888:Wechsler Scales
chemical_list: D004872:Ergocalciferols; D007004:Hypoglycemic Agents; D007328:Insulin; D014815:Vitamins