J Clin Neurol.  2015 Jan;11(1):66-72. 10.3988/jcn.2015.11.1.66.

The Effects of Galantamine Treatment on Attention and Its Relationship with Cognition and Activities of Daily Living in Patients with Mild to Moderate Alzheimer's Disease

• Lee JH
• Hong YJ
• Bae HJ
• Kim BJ
• Na DL
• Han SH
• Park JM
• Jeong JH
• Cha KR

• KMID: 2179574
• DOI: http://doi.org/10.3988/jcn.2015.11.1.66

Abstract

BACKGROUND AND PURPOSE
The positive effects of galantamine on cognition and activities of daily living (ADL) in Alzheimer's disease (AD) are thought to be mediated via improvements in attention. The purpose of this study was to determine the effect of galantamine on attention in AD patients using a computerized attention test and to elucidate the relationship between improvements in attention and change in cognition and ADL.
METHODS
In this multicenter, open-label, prospective study, patients with mild to moderate AD received galantamine and then submitted to computerized attention tests, the Alzheimer's Disease Assessment Scale-cognitive subscale, and instrumental ADL (IADL) at baseline, 4 weeks, and 12 weeks. The differences in reaction time on computerized tests were explored relative to the changes in cognition and IADL.
RESULTS
After 12 weeks of taking the trial medication there was a significant reduction from baseline levels in the choice reaction time (baseline, 5,216+/-3,650 sec; 12 weeks, 4,139+/-2,920 sec; p<0.01) and the simple reaction time (baseline, 1,089+/-782 sec; 12 weeks, 908+/-606 sec; p<0.01). Correlation analyses of changes in choice or simple reaction times relative to cognition and ADL measures yielded no significant associations. The improvement in attention observed at 4 weeks of galantamine treatment was not associated with any significant changes in outcome measures at the end of trial.
CONCLUSIONS
This study found no significant association between the improvement in attention after treatment with galantamine and changes in cognition and ADL in patients with mild to moderate AD, despite the significant improvement in attention over the course of the treatment.

Keyword

Alzheimer's disease; galantamine; attention; computerized test

MeSH Terms

Activities of Daily Living*
Alzheimer Disease*
Cognition*
Galantamine*
Humans
Outcome Assessment (Health Care)
Prospective Studies
Reaction Time
Galantamine

Figure

• 

  Fig. 1 Computer tests for the simple reaction time (SRT) and the choice reaction time (CRT). A: To determine the SRT, a subject is asked to respond to the computer screen changing from a white to a black color. The time taken to respond is measured. B: To determine the CRT, a single card is presented at the center of the screen and then four similar-looking cards are presented. The subject must choose the card that matches the previously shown card. The time taken to respond correctly is measured.

• 

  Fig. 2 Longitudinal changes in attention function over 12 weeks of trial medication. p<0.01 from paired t-test between choice reaction time (CRT) and simple reaction time (SRT), comparison of the score at the end of trial with the baseline score.

Reference

1. Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cholinesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004; 21:453–478.

2. Whitehead A, Perdomo C, Pratt RD, Birks J, Wilcock GK, Evans JG. Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer's disease: a meta-analysis of individual patient data from randomised controlled trials. Int J Geriatr Psychiatry. 2004; 19:624–633.

3. Suh GH, Jung Hee Yeon, Lee Chang Uk, Oh Byoung Hoon, Bae Jae Nam, Jung HY, et al. A prospective, double-blind, community-controlled comparison of three doses of galantamine in the treatment of mild to moderate Alzheimer's disease in a Korean population. Clin Ther. 2004; 26:1608–1618.

4. Farlow M, Anand R, Messina J Jr, Hartman R, Veach J. A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer's disease. Eur Neurol. 2000; 44:236–241.

5. Brousseau G, Rourke BP, Burke B. Acetylcholinesterase inhibitors, neuropsychiatric symptoms, and Alzheimer's disease subtypes: an alternate hypothesis to global cognitive enhancement. Exp Clin Psychopharmacol. 2007; 15:546–554.

6. Kadir A, Almkvist O, Wall A, Långström B, Nordberg A. PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease. Psychopharmacology (Berl). 2006; 188:509–520.

7. Daiello LA, Ott BR, Festa EK, Friedman M, Miller LA, Heindel WC. Effects of cholinesterase inhibitors on visual attention in drivers with Alzheimer disease. J Clin Psychopharmacol. 2010; 30:245–251.

8. Belleville S, Chertkow H, Gauthier S. Working memory and control of attention in persons with Alzheimer's disease and mild cognitive impairment. Neuropsychology. 2007; 21:458–469.

9. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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. 1984; 34:939–944.

10. Wilcock GK, Lilienfeld S, Gaens E. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine International-1 Study Group. BMJ. 2000; 321:1445–1449.

11. Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C. A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology. 2000; 54:2269–2276.

12. Wilkinson D, Murray J. Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 2001; 16:852–857.

13. Feldman H, Gauthier S, Hecker J, Vellas B, Emir B, Mastey V, et al. 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. J Am Geriatr Soc. 2003; 51:737–744.

14. Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ, et al. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003; 348:1333–1341.

15. Galvin JE, Cornblatt B, Newhouse P, Ancoli-Israel S, Wesnes K, Williamson D, et al. Effects of galantamine on measures of attention: results from 2 clinical trials in Alzheimer disease patients with comparisons to donepezil. Alzheimer Dis Assoc Disord. 2008; 22:30–38.

16. Gorus E, Lambert M, De Raedt R, Mets T. The influence of galantamine on reaction time, attention processes, and performance variability in elderly Alzheimer patients. J Clin Psychopharmacol. 2007; 27:182–187.

17. Jones GM, Sahakian BJ, Levy R, Warburton DM, Gray JA. Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease. Psychopharmacology (Berl). 1992; 108:485–494.

18. Albuquerque EX, Pereira EF, Alkondon M, Schrattenholz A, Maelicke A. Nicotinic acetylcholine receptors on hippocampal neurons: distribution on the neuronal surface and modulation of receptor activity. J Recept Signal Transduct Res. 1997; 17:243–266.

19. Lawrence AD, Sahakian BJ. Alzheimer disease, attention, and the cholinergic system. Alzheimer Dis Assoc Disord. 1995; 9:Suppl 2. 43–49.

20. Perry RJ, Hodges JR. Attention and executive deficits in Alzheimer's disease. A critical review. Brain. 1999; 122(Pt 3):383–404.