ERP Characteristics of Early AD I. Hakan Gürvit Istanbul University, Istanbul Faculty of Medicine, Department of Nuerology, Behavioral Neurology and Movement Disorders Unit

Background Spatio-temporal distribution of NFT pathology correlates with the symptom profile in AD (Mesulam 2000) According to Braak and Braak staging NFT pathology starts in the core limbic structures (MCI), and then spreads to heteromodal neocortical areas, posterior cortices being involved relatively earlier than the prefrontal cortex (DAT).

Background P300 wave P3a and P3b Oddball paradigm Novelty paradigm 2 different acoustic stimuli An actively engaged subject detects rarer target stimuli (T) amongst a train of standard stimuli (S) Attending T evokes a positive wave around 300 msec post-stimulus, with a highest amplitude parieto-centrally P3a and P3b Novelty paradigm In addition to T and S, novel even rarer sound stimuli (N) are interspersed in the train. N evokes an earlier, anteriorly located positive deflection (P3a), while T’s still evoke the expected more posterior and later positive wave (P3b).

Background ERP’s in AD The early components (P50 and MMN) related to the pre-conscious processing are generally normal Generators located in primary sensory and upstream unimodal sensory association cortices The late components (P300 and N400) related to the conscious processing are generally impaired (Polich et al, 1990; Gordon et al 1989) Generators located in heteromodal association areas

Objective The abnormality in the P3 wave which is an index of sustained attention might be demonstrated more reliably in the presence of distractors (novelty P3b) The abnormality in the P3a wave which is mediated by the prefrontal cortex and which is an index of novelty detection might be a relatively late phenomenon in AD.

Methods 11 very mild to mild (5 CDR 0.5, 6 CDR1), 11 moderate stage DAT patients (CDR 2) and 15 normal controls Groups are matching in terms of age, education and sex. Classical ERP recording according to 10-20system P3b with classical auditory oddball paradigm P3b and P3a with auditory novelty paradigm Statistical analysis with repeated measures ANOVA for the P3b and P3a amplitudes and latencies from the electrode sites Fz, Cz, Pz Combined AD group vs. normals Mild AD vs. Moderate AD vs. Normals

Results-Classical P3 Combined AD vs. Normals The comparison of P3 latency and amplitude between 2 goups is not significant

Results-Novelty P3b Combined AD vs. Normals AD group showed significantly lower P3b amplitudes at Pz (p<.001; P3b latencies were no different

Results-Novelty P3a Combined AD vs. Normals P3a latency was significantly prolonged in the AD group (p<.05); amplitude reduction in the AD group was close to significance (p=.051)

Results-Classical P3 Triple Comparison The comparison of latency and amplitude of P3 among 3 groups were not significantly different

Time-Frequency Analysis A continuous wavelet transform for computing time-frequency transforms. A late delta component is significantly increased in mild patients vs. both controls and moderate patients.

Results-Novelty P3b Triple Comparison Both of the AD groups had significantly lower P3b amplitudes at Pz as compared to controls (p=.003); latency differences between the groups were not significant

Results-Novelty P3a Triple Comparison P3a latency of the moderate AD group was significantly prolonged as compared to both normal (p<.001) and mild AD group (p<.05); amplitude differences were not significant

Results-Topography

Conclusions The latency of P3a discriminates the moderate from the mild stage. Novelty P3b the mild stage from the normals. The controversy regarding the classical oddball paradigm in AD might be due to the frontal compansation in the mild stage (Friedman 1997).