209 Unawareness of memory impairment in dementia of Alzheimer type and cerebrovascular disease

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FIFTH INTERNATIONAL CONFERENCE ON ALZHEIMER'S DISEASE

Neurosciences and Psychiatry, University of Newcastle upon Tyne, NE1 4LP, England. 3 Cognitive Drug Research Limited, Priory Court, Beech Hill, Reading, RG7 2B J, England. Computerised psychological assessment provides a useful tool in clinical and neuropsychological settings. Subtle cognitive deficits may be missed using standard psychometric assessment tools. Tasks which require precise stimulus presentation times, measures of latency to respond, and accuracy of responses benefit from computerisation. Two computerised assessment systems have been employed to compare cognitive and neuropsycholgical profiles in patients who suffer from Dementia with Lewy Bodies (DLB) and Senile Dementia of the Alzheimer's Type (SDAT). Comparative data is presented from a series of assessments using both the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Cognitive Drug Research (CDR) assessment battery. CANTAB has demonstrated that DLB patients are more severely impaired than SDAT in cognitive functioning associated with frontal lobe and nigrostriatal pathways such as attentional flexibility, spatial working memory and planning. The CDR assessment system has specific modifications to allow inclusion of patients with more severe giobal dementia, and as such is a powerful tool for longitudinal investigation of the nature and course of cognitive decline, Data from an ongoing study in Newcastle suggests attentional function is relatively impaired in DLB compared to SDAT, whilst mnemonic processes appear to be relatively spared in DLB. Novel computerised assessment procedures are being developed to further delineate DLB and SDAT.

206 Detection and staging of cognitive decline in mild AIzheimer's disease M. Uno, T. Asada, Y. Takayama, H. Matuda, M. Nakano and T. Motonaga Department of Psychiatry, National Musashi Hospital, NCNP, 4-1-10gawaHigashi, Kodaira Tokyo 187, Japan Objective: To differentiate questionable Alzheimer's disease (AD) from normal aging with benign senescent forgetfulness, and to detect predictors of progression of cognitive decline to mild DAT using interview-based clinical symptoms and neuropsychological measures, and with quantitative SPECT assessment of regional cerebral blood flows (rCBF). Method: Twenty nondemented patients who complained forgetfulness, 20 questionable and 20 mild AD patients were selected among memory clinic patients. The subject evaluation procedure consisted of informant interview dealing with changes in memory and intelligence which had taken place in the previous 5 years, neuropsycologieal testing which included logical memory and word list memory immediately and with a delay of 30 minutes, and radioactive 99m'Tc ECD SPECT assessment of mean and regional CBE Results: (1) Scores from the interview were found to correlate (r=-0.73) with Mini-Mental State Examination. Items which were concerned with cognitive performance in everyday activities such as cooking task and house keeping, and with spatial orientation observed in the abilityof transport such as travel independently on public transports, had predictive value for progression of dementia to further stage. (2) Delayed recall of logical and word list memory are best to distinguish between benign forgetfulness and malignant memory impairment. (3) Decrease of r CBF in the medial temporal region was the common finding in questionable AD, and when the questionable (possible) AD developed to mild stage of probable AD, there occurred decrease of rCBF in the bilateral posterior temporoparietal region together with decrease of mean CBE ConcluMons: AIzheimer's disease was able to be diagnosed reliably using informant -based clinical pictures, neuro-psychometric measures and radiological assessment at its very early stage, and the progress of cognitive decline to further stage was suggested by items which were concerned with manual task impairment and spatial disorientation, and by decrease of rCBS in bilateral temporoparietal areas.

207 A comparison of memory profiles of dementia of the Alzheimer's type and antieholinergic agent-induced cognitive dysfunction Y. Morokawa*, H. Watanabe, T. Ohta, Y. Nagatsu, H. Fujimaki, M. Kamimura, N. Yamaguchi and A. Aoba

Department of Psychiatry, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamaeku, Kawasaki 216, Japan To investigate the effects of plasma antieholinergie level on cognitive dysfunction induced by biperiden, an anticholinergie agent, a cognitive function test battery was administered to four groups of subjects, a dementia of the Alzheimer's type group (DAT, N=I 1), a chronic biperiden administration group (CBPR, N=I 1), an acute biperiden administration group (ABPR, N=I 1) and an age-matched control group (CTL, N=10). The cognitive function test battery included the following six items: immediate verbal recall (IVR), delayed verbal fecal I (DVR), delayed verbal recognition (DVRG), Ietter cancellation test (LCT), reaction time (RT) and code substitution (CS). Plasma antieholinergie level was also determined by radioreceptor assay using 3H-QNB before and 1, 3 and 7 hours after biperiden injection. The average values of plasma anticholinergie level were significantly increased and average 1VR, DVR, DVRG and LCT scores were significantly decreased one hour after the injection as compared to those before injection. Significant differences in fore of six cognitive function test scores between the CBPR and DAT groups were observed. However, these differences disappeared after BPD injection for the ABPR and DAT groups. The similarities of the cognitive dysfunction profiles between these two groups strongly support the acetylcholine hypothesis for dementia of Alzheimer's type.

208 Detection of Abnormal Memory Decline in Early-Stage Dementia of The Alzheimer's Type - A Six-Month Prospective Study N. Yamaguchi*, Y. Morokawa, H. Watanabe, M. Kamimura, Y. Hirakawa, Y. Hirakawa, T. Ohta, M. Kishiro, H .Fujimaki, A. Onodera, M. Tagnehi, N. Okuyama, Y. Nagatsu and A. Aoba Department of Psychiatry, St. Marlanna University School of Medicine, 2-16-1, Sugao, Miyamaeku, Kawasaki 216, Japan The purpose of our study is to differentiate psychometrically abnormal memory decline in early-stage dementia of the Alzheimer's type (DAT) from memory impairment in healthy individuals. Forty-nine subjects (mean age: 71.0 4- 7.6) with complaints of memory loss were divided into nondemented (ND, N=I7), borderline (BD, N=19) and demented (D, N=13) groups, according to DSM- IV and Functional Assessment Staging (FAST). The memory test battery, which included immediate verbal recall (IVR), delayed verbal recall (DVR) and delayed verbal recognition (DVRG), was performedfor all subjects. After a six-month study on the 19 subjects of the BD group.using the memory test battery, 13 of them were rediagnosed as having DAT (subgroup BD2) while the rest were considered BD (subgroup BD1). We found that the mean scores for each memory test conducted on subjects of the D group were the lowest and those for the test conducted on subjects of the ND group were the highest. The mean scores for each memory test conducted on subjects of the BD2 group were significantly lower than those of the BD1 group (p<0.001) and were closely similar to those for the conducted on subjects of the D group. The difference in scores for the memory tests conducted on subjects from the BDI and BD2 groups was large in the order ofDVR > IVR > DVRG. These results suggest that IVR, DVR and DVRG were useful measures for the early detection of DAT and that the test for DVR might be the most discriminatory in our test battery.

209 Unawareness of memory impairment in dementia of AIzheimer type and cerebrovascular disease M. Nakanishi*l),T. Hamanaka 1), S. Yoshida l), S. NakaakP) and K. Hadano2) 1): Department of Psychiatry, Nagoya City University School of Medicine, 1 Kawasumi Mizuho-cho Mizuho-ku Nagoya 467, Japan 2): Department of Psychogeriatrics, National Institute of Mental Health, National Center of Neurology and Psychiatry In order ta evaluate the difference in unawareness (UA) of memory impairment between patients with dementia of Alzheimer type (DAT) and those with cerebrovascular disease (CVD), we adoministered a self-report "Memory Questionaire" (MQ) and a battery of neuropsychological tests to 22 patients with DAT, the severity of which was mild or slightly moderate according to the DSM-III-R criteria for dementia, and 20 with CVD whose memory performances

FIFTH I N T E R N A T I O N A L C O N F E R E N C E ON A L Z H E I M E R ' S D I S E A S E

were impaired without other severe cognitive deficits. MQ is composed of two forms, patient's MQ with 132 items and family member's MQ with 104 items, and is divided into the following four subscales. The first subscale asks about memory impairment regarding general events from recent daily life. The second is concerned with difficulties associated with perceptive, physical and cognitive symptoms except for those of memory impairment. The third is concerned with recall deficits of hypothetical important events in daily life after delays of 10 minutes, 1 hour, 1 day and I week. The fourth asks how many of 10 words the subject can recall after delays of the same time spans as above. UA-scores were operationally obtained by subtracting patients' ratings of their own memory impaired symptoms from those by their family member. There were no significantly difference in intellectual performancebetween two groups. However, DAT patient's UA-scores were significantly higher than those of memory impaired CVD patients in the 1st subscale, the 2nd, the 3rd after delays of 10 minutes and over, and the 4th after delays of 10 minutes. We conclude that there is a difference in UA of memory impairment between DAT and CVD, and that UA of memory impairment contributes to the differential diagnosis between the two diseases.

210 Non-Attentinnal Event-related potentials in Age-Associated Memory Impairment Hallikainen M*, Pii/ikk6nen A, Karhu J, H~inninen T, Riekkinen P Sr, Soininen H Depts of Neurology and Clinical Neuropbysiology, University Hospital of Kuopio, P.O.Box 1627, 70211 Kunpio, Finland Different diagnostic definitions have been proposed for use in the characterization of mild cognitive disorders associated with aging. We have conducted a fullow-up study of Age-Associated Memory Impairment (AAMI) subjects to better characterize AAMI and its natural clinical course. In our 3.6-year follow-up period, 9.1% of the AAMI subjects developed dementia (H/inuinen et al 1995). In this study, we approached AAMI from functional aspects by using electrophysiologicalmethods. We recorded auditory and visual event-related potentials in 43 subjects fidfilllng the National Institute of Mental Health criteria of AAMI (Crook et al 1986) and in 46 healthy age-matched controls. We found enhanced amplitudes and shortened lateneies in multimodal ERPs as well as clearly impaired habituation of auditory N100 in non-attended conditions. Since habituation reflects automatic focusing of attention to relevant features of stimuli, impairment of this mechanismand subsequent defective memory trace formation may contribute to observed deficits in memory tests in AAMI. These findings suggest that Age-Associated Memory Impairment could be Age-Associated Attentional Impairment or that involuntary attention deficit could at least partly explain memory impairment in AAMI subjects.

211 Evolution of Memory Impairments in Patients with Alzheimer's Disease S. Groppa* and C. Guranda Department of Neurology, Medical State University N. Testemitseanu, 4336 Cuza Voda str., Chisinau 2072, Republic of Moldova We examined 72 patients with Alzheimer's Disease. The diagnosis was established according to NINCDS-ADRDA criteria. For the estimation of the mental functions we used standard tests, based on A.Luria (1973) method. We also used Sandoz (R.Venn, 1983) scale of Gerontology examination and the scale for estimation of everyday activity (CIPS, 1986). The obtained results indicated prevalent diminish of the visual short term memory. Already at the initial stages of the disease all the patients had difficulties in reproduction of the given visual forms. Nobody could remembered 5 proposed figures, even if the test was repeated several times. On later stages of the disease this method was impossible to use. The examination of the acoustic-verbal functions at the onset of the disease revealed defects of the cognitive abilities, increased hindrance

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of the traces by interfering interaction and phenomenon of proactive hampering. Evident dismnestic disturbances were found out in 100% patients at the stage of moderate manifestations. Significant reduce of the learned volume was established. Heterogeneous interferation lead to the absence of reproduction. In the severe stages o f the disease the volume of the learned material was significantly reduced. The patients memorised not more then 1-2 words. Phenomenon of proaetive hampering was usual. The long term memory loss wasn't so evident as the short term memory loss. At the initial stages of the disease the patients correctly indicated the autobiographic data, named the family members. During the process o f the disease evolution more pronounced dysfunction of the tong term memory was noticed. The results of the neuropsychologial investigations indicates gradually barely noticeable increase of the dismnestic disturbances with successive total disintegration of the mental-mnestic functions.

212 Disturbances in mental rotation and eye movements of the patients with AIzheimer's disease. K. Utsumi*, S. Hayashi, R. Fukatsu, Y. Midorikawa, N. Nakano, S. Murakami, M. Fujii, and N. Takahata Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, SIWI6, Sapporo 060, Japan Constructional apraxia is one of the neuropsychologicalfindings frequently observed in the early stage of the Alzheimer's disease, which may result from the visuo-spatial disturbances. "Reversible operation in space", the ability to spatially rotate objects on the level of thought, plays important role in visuospatial functions and also in the constructional praxia. The operation is generally carried out after integration of viewer-centered coordinate system with objects-centered coordinate system. We have reported that the patients with AD even in the early stage had difficulties in operation of visual coordinate system during the perspectivetasks. In this study, we investigated the ability of mental rotation and eye movements while performing tasks in patients with Alzheimer's disease. The subjects were 15 patients with Alzheimer's disease (AD group), 10 patients with multi-infarcts dementia as disease control (MID group), 15 age matched persons as healthy control (HC group). AD group was divided into the early stage group(AD-ear.) and the advanced stage group(AD-adv.) according to Clinical Dementia Sealing's score. Examiner asked subjects to select from the four alternatives in the lower row the one identical to the standard figure rotated 180 degrees in its front-parallel plane. This task was composed of 10 items, that was modified from Butters and Barton's "pool reflection test". Eye movements were detected by vision analyzer, and were superimposed at real time on video monitor on which a micro video camera fixed on a subject's forehead projected the test card they were looking at. The performance of the AD-adv. was significantly poorer than the performance of the MID, and the HC. Also the AD-ear. made more errors than did the MID, and the HC. This result clearly demonstrate that the patients with Alzheimer's disease have disturbance in reversible operation in space. Analysis of eye movements in performing the task showed that gazing points in some of the AD-adv. were fixed at positions away from figures, and that they rarely searched four altemalive figures. These findings indicate that the difficulty in mental rotation are involved with visuo-spatial dysfunctions in the patients with Alzheimer's disease, and the disturbances in eye movements may reflect disturbed thinking or visuospatial cognitive functions.

213 DEPTH COGNITIVE IMPAIRMENT IN ALZHEIMER'S DISEASE: RECORDING BINOCULAR EYE MOVEMENT S. Murakami*, M. Fujii, K. Uomori, R. Fukatsu, N. Nakano, M. Yamada, S. Hayashi, Y. Midorikawa, K. Utsumi and N. Takahata Dep. of Neuropsychiatry, School of Medicine, Sapporo Medical University,Sapporo 060, Japan An early visuospatial cognitive impairment was observed in a patient with Alzheimer's disease(AD). However, depth cognitive impairment in space was not studied systematically in AD. The depth space cognition in normal controls and AD patients was studied by recording binocular eye movement and vergence angle using by vision analyzer(Takei Co.). The visual