The study goal is to advance our ability to diagnose patients with dementia of the Alzheimer's type (DAT) early in the disease process using a relatively simple, noninvasive, less-expensive, diagnostic test for DAT involving the pupillary light reflex and tropicamide blockade of ocular cholinergic functions. This will be accomplished using pupillographic methods to examine pupillary responses to light pulses during double-blind peripheral (ocular) administration of tropicamide and saline solutions in patients with DAT, patients with Parkinson's Disease (PH), and normal controls. A recent preliminary report by Scinto et al. (1994) found some promising results suggesting abnormally increased pupillary dilation responses in patients with DAT during administration of a very dilute solution of the acetylcholine-blocking drug tropicamide. To date, some studies have reported findings which are consistent with the Scinto et al. (1994) findings of supersensitivity of cholinergic ocular-motor systems in DAT (Katz, 1995; Pomara & Sitaram, 1995), but no study has directly replicated the Scinto et al. results, and some studies have failed to replicate findings in the Scinto et al. study (Marquard et al., 1995; Marx et al., 1996; Treloar & Assin, 1995). Therefore, the proposed study has the following specific aims:
Aim 1 : To employ a more rigorous methodology than has been used in previous studies to challenge cholinergic oculomotor functions in DAT. Pupillary responses to light pulses will be recorded during double-blind peripheral (ocular) administration of tropicamide and saline solutions. In the peripheral autonomic nervous system, the pupillary light reflex is largely a parasympathetic, cholinergic response. Thus, the combination of these psychophysical (light reflex) and pharmacologic (tropicamide) methodologies will impose a more demanding challenge of acetylcholine-mediated oculomotor functions in DAT patients.
Aim 2 : To determine whether employing these more rigorous convergent psychophysical and pharmacologic methods provides a diagnostic test for DAT.
Aim 3 : To determine whether measures of the pupillary light reflex, alone (i.e., recorded without tropicamide), might provide an even more noninvasive diagnostic test for DAT.
Aim 4 : To attempt to replicate the Scinto et al. (1994) study in a larger sample of patients with DAT, as compared to demented PD patients and age-matched controls. Promising pilot data showed differentiation of DAT and normal control subjects using measures of the pupillary light reflex, and these measures showed even better separation of groups when recorded during tropicamide administration.
| Granholm, Eric; Morris, Shaunna; Galasko, Douglas et al. (2003) Tropicamide effects on pupil size and pupillary light reflexes in Alzheimer's and Parkinson's disease. Int J Psychophysiol 47:95-115 |
| Granholm, E; Morris, S; Asarnow, R F et al. (2000) Accelerated age-related decline in processing resources in schizophrenia: evidence from pupillary responses recorded during the span of apprehension task. J Int Neuropsychol Soc 6:30-43 |
| Granholm, E; Chock, D; Morris, S (1998) Pupillary responses evoked during verbal fluency tasks indicate semantic network dysfunction in schizophrenia. J Clin Exp Neuropsychol 20:856-72 |
