Pupil reaction to light in Alzheimer’s disease: evaluation of pupil size changes and mobility Authors
First Online: 25 July 2013 Received: 24 May 2006 Accepted: 24 January 2007 DOI:
Cite this article as: Fotiou, D.F., Brozou, C.G., Haidich, A. et al. Aging Clin Exp Res (2007) 19: 364. doi:10.1007/BF03324716 Abstract
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.
Keywords Acetylcholine Alzheimer’s disease autonomic nervous system dementia pupillometry References
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.
Rowe J, Kahn R. Human aging: usual and successful. Science 1987; 237: 143–9.
Rapp P, Amaral D. Individual differences in the cognitive and neurobiological consequences of normal aging. Trends Neurosci 1992; 15: 340–5.
Ascher KW. The first pupillary light reflex test ever performed. Trans Am Ophthalmol Soc 1962; 60: 53–9.
Ascher KW. The first test of the Pupillary Reflex to Light. Boll Ocul 1963; 42: 586–91.
Thompson HS. Adie’s syndrome: some new observations. Trans Am Ophthalmol Soc 1977; 75: 587–626.
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.
Pomara N, Sitaram N. Detecting Alzheimer’s disease. Science 1995; 267: 1959–60.
Scinto LFM, Daffner KR, Dressler D, et al. A potential noninvasive neurobiological test for Alzheimer’s disease. Science 1994; 266: 1051–3.
Loupe DN, Newman NJ, Green RCl, et al. Pupillary response to tropicamide in patients with Alzheimer disease. Ophthalmology 1996; 103: 495–503.
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.
Kardon RH. Drop the Alzheimer’s drop test. Neurology 1998; 50: 588–91.
Marx JL, Kumar SR, Thach AB, Kiat-Winarko T, Frambach DA. Detecting Alzheimer’s disease. Science 1995; 267: 1577; author reply 1580–1.
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.
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.
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.
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.
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.
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.
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.
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.
Loewenfeld IE. The Pupil: Anatomy, Physiology and Clinical Applications. Boston — Oxford: Butterworth-Heinemann, 1999.
Wilhelm H, Kardon RH. The papillary light reflex pathway. Neurophthalmology 1997; 17: 59–62.
Lowenstein O, Loewenfeld IE. The Pupil. In Davson H, Ed. The Eye. New York: Academic Press, 1962: 231–67.
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.
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.
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.
Appleyard M, McDonald B. Reduced adrenal gland acetyl-cholinesterase activity in Alzheimer’s disease. Lancet 1991; 338: 1085–6.
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.
Altman D. Practical Statistics for Medical Research. London: Chapman and Hall, 1991.
Sullivan Pepe M. The statistical evaluation of medical tests for classification and prediction. Oxford University Press, 2004.
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.
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.
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.
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.
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.
Pavlovsky L, Browne RO, Friedman A. Pyridostigmine enhances glutamatergic transmission in hippocampal CA1 neurons. Exp Neurol 2003; 179: 181–7.
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.
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.
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