Aging Clinical and Experimental Research

, Volume 19, Issue 5, pp 364–371 | Cite as

Pupil reaction to light in Alzheimer’s disease: evaluation of pupil size changes and mobility

  • Dimitris F. Fotiou
  • Catherine G. Brozou
  • Anna-Bettina Haidich
  • Dimitris Tsiptsios
  • Maria Nakou
  • Anastasia Kabitsi
  • Charalambos Giantselidis
  • Fotis Fotiou
Original Articles


Aims: The aim of the study is to assess pupil size changes and mobility evaluation as a diagnostic marker in patients with probable Alzheimer’s disease (AD). Material and methods: Twenty-three control subjects and 23 patients with probable AD entered the study. The latter patients had been under observation for 2 years and had undergone all necessary examinations to verify their initial diagnosis. A full record of the pupil’s reaction to light was registered. Ten parameters from these data were measured, reported and then compared in both group of subjects. Results: Patients with probable AD had abnormal pupillary function compared with such function in healthy aging. All pupillary light reflex (PLR) variables differed significantly between the two groups (p<0.005) except baseline pupil diameter (D1) and minimum pupil diameter (D2). Maximum constriction acceleration (ACmax) was the best predictor in classifying a subject as normal or as AD with perfect classification ability (area under the curve =1, p<0.001). In addition, the correlation between the percentage recovery-redilatation (%D1) and ACmax was highly negative in the group of AD patients (r=−0.808, p<0.005). Conclusions: Pupil size changes and mobility examination may be a fast, non-invasive and efficient additional diagnostic marker in AD diagnosis.


Acetylcholine Alzheimer’s disease autonomic nervous system dementia pupillometry 


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  1. 1.
    Solomon PR, Murphy CA. Should we screen for Alzheimer’s disease? A review of the evidence for and against screening for Alzheimer’s disease in primary care practice. Geriatrics 2005; 60: 26–31.PubMedGoogle Scholar
  2. 2.
    Rowe J, Kahn R. Human aging: usual and successful. Science 1987; 237: 143–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Rapp P, Amaral D. Individual differences in the cognitive and neurobiological consequences of normal aging. Trends Neurosci 1992; 15: 340–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Ascher KW. The first pupillary light reflex test ever performed. Trans Am Ophthalmol Soc 1962; 60: 53–9.PubMedGoogle Scholar
  5. 5.
    Ascher KW. The first test of the Pupillary Reflex to Light. Boll Ocul 1963; 42: 586–91.PubMedGoogle Scholar
  6. 6.
    Thompson HS. Adie’s syndrome: some new observations. Trans Am Ophthalmol Soc 1977; 75: 587–626.PubMedGoogle Scholar
  7. 7.
    Idiaquez J, Alvarez G, Villagra R, San Martin RA. Cholinergic supersensitivity of the iris in Alzheimer’s disease. J Neurol Neurosurg Psychiatr 1994; 57: 1544–55.PubMedCrossRefGoogle Scholar
  8. 8.
    Pomara N, Sitaram N. Detecting Alzheimer’s disease. Science 1995; 267: 1959–60.CrossRefGoogle Scholar
  9. 9.
    Scinto LFM, Daffner KR, Dressler D, et al. A potential noninvasive neurobiological test for Alzheimer’s disease. Science 1994; 266: 1051–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Loupe DN, Newman NJ, Green RCl, et al. Pupillary response to tropicamide in patients with Alzheimer disease. Ophthalmology 1996; 103: 495–503.PubMedGoogle Scholar
  11. 11.
    Treloar AJ, Assin M, MacDonald AJD. Pupillary response to topical tropicamide as a marker of Alzheimer’s disease. Br J Clin Pharmacol 1996; 41: 256–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Kardon RH. Drop the Alzheimer’s drop test. Neurology 1998; 50: 588–91.PubMedCrossRefGoogle Scholar
  13. 13.
    Marx JL, Kumar SR, Thach AB, Kiat-Winarko T, Frambach DA. Detecting Alzheimer’s disease. Science 1995; 267: 1577; author reply 1580–1.Google Scholar
  14. 14.
    Sacks B, Smith S. People with Down’s syndrome can be distinguished on the basis of cholinergic dysfunction. J Neurol Neurosurg Psychiatr 1989; 52: 1294–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Prettyman R, Bitsios P, Szabadi E. Altered pupillary size and darkness and light reflexes in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1997; 626: 665–8.CrossRefGoogle Scholar
  16. 16.
    Fotiou F, Fountoulakis KN, Tsolaki M, Tsorlinis H, Goulas A, Alexopoulos L. Changes in the pupil reaction to light in Alzheimer’s disease patients. Int J Psychophysiol 1998; 30: 412.Google Scholar
  17. 17.
    Fotiou F, Fountoulakis KN, Tsolaki M, Goulas A, Palikaras A. Changes in pupil reaction to light in Alzheimer’s disease patients: a preliminary report. Int J Psychophysiol 2000; 37: 110–20.CrossRefGoogle Scholar
  18. 18.
    Tales A, Troscianko T, Lush D, Haworth J, Wilcock GK, Butler SR. The pupillary light reflex in aging and Alzheimer’s Disease. Aging Clin Exp Res 2001; 13: 473–78.Google Scholar
  19. 19.
    Granholm E, Morris S, Galasko D, Shults C, Rogers E, Vukov B. Tropicamide effects on pupil size and pupillary light reflexes in Alzheimer’s and Parkinson’s disease. Int J Psychophysiol 2003; 47: 95–115.PubMedCrossRefGoogle Scholar
  20. 20.
    Fountoulakis KN, Kaprinis G, Fotiou F. Is there a role for pupillometry in the diagnostic approach to Alzheimer’s disease? A review of the data. J Am Geriatr Soc 2004; 52: 166–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Ferrario E, Molaschi M, Villa L, Varetto O, Bogetto C, Nuzzi R. Is videopupillography useful in the diagnosis of Alzheimer’s disease? Neurology 1998; 50: 642–4.Google Scholar
  22. 22.
    Loewenfeld IE. The Pupil: Anatomy, Physiology and Clinical Applications. Boston — Oxford: Butterworth-Heinemann, 1999.Google Scholar
  23. 23.
    Wilhelm H, Kardon RH. The papillary light reflex pathway. Neurophthalmology 1997; 17: 59–62.CrossRefGoogle Scholar
  24. 24.
    Lowenstein O, Loewenfeld IE. The Pupil. In Davson H, Ed. The Eye. New York: Academic Press, 1962: 231–67.Google Scholar
  25. 25.
    Ichikawa T, Shimizu T. Organization of choline acetyltransferase obtaining structures in the cranial nerve motor nuclei and spinal cord of the monkey. Brain Res 1998; 779: 96–103.PubMedCrossRefGoogle Scholar
  26. 26.
    Trick G, Barris M, Bickler-Bluth M. Abnormal pattern electroretinogram in patients with senile dementia of the Alzheimer type. Ann Neurol 1989; 26: 226–31.PubMedCrossRefGoogle Scholar
  27. 27.
    Aharon-Peretz J, Harel T, Revah M, Ben-Haim S. Increased sympathetic and decreased parasympathetic cardiac innervation in patients with Alzheimer’s disease. Arch Neurol 1992; 49: 919–22.PubMedCrossRefGoogle Scholar
  28. 28.
    Appleyard M, McDonald B. Reduced adrenal gland acetyl-cholinesterase activity in Alzheimer’s disease. Lancet 1991; 338: 1085–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Folstein MF, Folstein, SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189–98.PubMedCrossRefGoogle Scholar
  30. 30.
    Altman D. Practical Statistics for Medical Research. London: Chapman and Hall, 1991.Google Scholar
  31. 31.
    Sullivan Pepe M. The statistical evaluation of medical tests for classification and prediction. Oxford University Press, 2004.Google Scholar
  32. 32.
    Bergamin O, Kardon R. Latency of the pupil light reflex: sample rate, stimulus intensity, and variation in normal subjects. Invest Ophthalmol Vis Sci 2003; 44: 1546–54.PubMedCrossRefGoogle Scholar
  33. 33.
    Yamaji K, Hirata Y, Usui S. A method for autonomic nervous activity by pupillary flash response. Systems and computers in Japan, Vol. 31, No. 4, 2000.Google Scholar
  34. 34.
    Smith SA, Smith SE. Pupil function: test and disorders. In Bannister R, Mathias CJ, Eds. Autonomic failure. A textbook of clinical disorders of the autonomic nervous system. Oxford: Oxford University Press, 1999.Google Scholar
  35. 35.
    Iijima A, Haida M, Ishikawa N, Ueno A, Minamitani H, Shinohara Y. Re-evaluation of tropicamide in the pupillary response test for Alzheimer’s disease. Neurobiol Aging 2003; 24: 789–96.PubMedCrossRefGoogle Scholar
  36. 36.
    Roldan-Tapi L, Leyva A, Laynez F, Santed FS. Chronic neuropsychological sequelae of cholinesterase inhibitors in the absence of structural brain damage: two cases of acute poisoning. Environ Health Perspect 2005; 113: 762–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Pavlovsky L, Browne RO, Friedman A. Pyridostigmine enhances glutamatergic transmission in hippocampal CA1 neurons. Exp Neurol 2003; 179: 181–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Brenner T, Hamra-Amitay Y, Evron T, Boneva N, Seidman S, Soreq H. The role of readthrough acetylcholinesterase in the pathophysiology of myasthenia gravis. FASEB J 2003; 17: 214–22.PubMedCrossRefGoogle Scholar
  39. 39.
    Grisaru D, Sternfeld M, Eldor A, Glick D, Soreq H. Structural roles of acetylcholinesterase variants in biology and pathology. Eur J Biochem 1999; 264: 672–86.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Internal Publishing Switzerland 2007

Authors and Affiliations

  • Dimitris F. Fotiou
    • 1
  • Catherine G. Brozou
    • 1
  • Anna-Bettina Haidich
    • 2
  • Dimitris Tsiptsios
    • 1
  • Maria Nakou
    • 3
  • Anastasia Kabitsi
    • 4
  • Charalambos Giantselidis
    • 1
  • Fotis Fotiou
    • 1
  1. 1.Laboratory of Clinical NeurophysiologyAHEPA HospitalThessalonikiGreece
  2. 2.Laboratory of HygieneUSA
  3. 3.Second Department of PsychiatryMedical School, Aristotle University of ThessalonikiThessalonikiGreece
  4. 4.Department of PsychologySaint Louis UniversityUSA

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