Receptor test (pupillary dilatation after application of 0.01% tropicamidesolution) and determination of central nervous activation (Fourier analysis of pupillary oscillations) in patients with Alzheimer's disease

Memory loss and severe cognitive deficits in Alzheimer patients are suppose d to be related to a reduction of acetylcholine as well as to central nervo us deactivation. For the investigation of cholinergic deficits and deactiva tion, we used computer-assisted pupillometry. Cholinergic deficits caused b y a particularly severe loss of cholinergic neurons may be responsible for cognitive and mnemonic performance deficits. The control of the pupillary d iameter represents a balance between cholinergic and adrenergic innervation and is influenced directly or indirectly by central and autonomic nervous system inputs. Either of these systems could be affected in Alzheimer patie nts. A reduced innervation of the target muscle through neuronal cell death , axon retraction, reduced release, increased reuptake of altered amounts o r function of neurotransmitter receptors seems to affect the pupillary resp onse to cholinergic antagonists in Alzheimer patients. There is, however, n o relationship between pupillary diameter and central deactivation, but bet ween central nervous activation and pupillary oscillations which reflect th e physiological corticodiencephalic activity, a relationship has to be assu med. Frequencies and amplitudes of pupillary oscillations measured by means of Fourier analysis are modulated corticodiencephalicaIly. Therefore, Alzh eimer patients were compared to healthy controls with respect to their pupi llary diameters and responses to an acetylcholine antagonist. Twenty-nine p atients, aged between 55 and 85 years, suffering from mild to moderate Alzh eimer's disease (AD) and 29 normal controls of similar age formed. Times of measurement were: 0 (baseline), 20, 40, 60, 80, and 100 min. After 4 min t ropicamide was instilled. Forty min after the instillation of tropicamide i nto the left eye, the Alzheimer patients showed a pronounced dilatation of 41.57%. The dilatation in normal controls was 28.5%. Fourier analysis of pu pillary oscillations (sum of frequency bands = power) demonstrated a marked deactivation (low amplitudes in low-frequency bands, but in contrast to ou r expectations no higher amplitudes in the higher frequency bands) in patie nts with AD which remained constant at all times of measurement. By means o f discriminant analysis of pupillary diameter and pupillary oscillations (f requency band 0.00-1 Hz), 89.7% were correctly predicted to be Alzheimer pa tients, 89% to be normal controls.(56-85 years) participated in the study. The cholinergic receptors of the pupil were blocked by the acetylcholine an tagonist tropicamide. It could be assumed that the larger the pupillary dil atation, the larger the extent of cognitive deficits. Alzheimer patients sh ow abnormal acetylcholine neurotransmission. Changes of pupillary diameter after instillation of 1 drop of 0.01% tropicamide solution were measured an d Fourier analysis of pupillary oscillations was performed. Times of measur ement were: 0 (baseline), 20, 40, 60, 80, and 100 min. After 4 min tropicam ide was instilled. Forty min after the instillation of tropicamide into the left eye, the Alzheimer patients showed a pronounced dilatation of 41.57%. The dilatation in normal controls was 28.5%. Fourier analysis of pupillary oscillations (sum of frequency bands = power) demonstrated a marked deacti vation (low amplitudes in low-frequency bands, but in contrast to our expec tations no higher amplitudes in the higher frequency bands) in patients wit h AD which remained constant at all times of measurement. By means of discr iminant analysis of pupillary diameter and pupillary oscillations (frequenc y band 0.00-1 Hz), 89.7% were correctly predicted to be Alzheimer patients, 89% to be normal controls.