ELSEVIER Journal of the Neurological Sciences 238 (2005) $277-$378

Journal o/Ihe

Ne o!ogical clences

www.elsevier, com/locate/jns

Poster Abstracts

9 November 2005

0696 Two Types of Abeta Removal by Glial Cells

Akiyama, H 1, KolldO, H 1, Haga, C 1, Slffmollmra, y 1 0 b i , K 2, Oshillla, K 3, Tsuctffya, K 3. 2Tokyo Institute of Psychiatry, Tokyo, Japan; 2Juntozdo University, Tokyo, Japan; 3Tokyo Metropolitan Ivlatsuzawa Hospital, Tokyo, Japan

Baekg*ound: In vitro and ill vivo studies have shown that, following intake by glial cells, amyloid-beta protein (Abeta) loses the epitopes of N-termillal sequence by illtracellular processing. In this study, we investigated the change of immunochemical profiles of Abeta together with the phenotypes of glial cells that accumulate Abeta intracellularly. Method: Postmortem brain tissues from patients with Alzheimer's disease were fixed in 4% paraformaldehyde, cryo-cut into free-floating sections and double-illmmnostailled for combinations of N- and C-terminal sequences of Abeta, Abeta and microglial markers, or Abeta and astrocyfic markers. Results: Accumulation of Abeta that lacks the N-terminal sequence was seen in both microglia and astrocytes. Phellotypes of these cells indicate that they are resting or modestly activated. Occurrence of such Abeta containing glial cells varied from patient to patient and from region to region in a given patient. Within senile plaques, highly- activated microglia that contain N-terminally modified Abeta were seen. Postmortem human brains are often complicated with mild ischemia/hypoxia that do not cause infarction but activate microglia. In senile plaques associated with such mild insults, illtrallffcroglial Abeta that was negative for the N-terminal sequence increased and extracelhilar Abeta that was positive for the N-terminal sequence decreased. Conclusions: Abeta is taken up by resting microglia/astrocytes as well as by reactive microglia. The latter process seems to be phago- cytosis o f once-deposited, insoluble Abeta aggregates. Deposition of Abeta in senile plaques may depend on the dynmnic balance between the addition of newly secreted Abeta and the removal by reactive microglia.

0697 Amnestie Mild Cognitive Itllpaixillent: Applicabilily of Research Criteria in a Memory Clinic and Defidls Beyond Amnesia

Alladi S l, Nestor pj2, Arnold R 2, Mitchell Ja, Hodges JR ~. ZNizam's Institute of Medical Sciences, Hyderabad, India; 2University of Cambridge, Neurology Unit, Cambridge, United Kingdom

Background: Mild Cognitive Impairment (MCI) as defined by Petersell's criteria is regarded as all amllestic state that represents prodromal Alzheimer's disease (AD). However, controversies exist regarding definition of amnesia in MC[ and involvement of other cognitive functions. We aimed to evaluate applicability of Petersen's

criteria ill a memory clinic, to assess how different lllelilory tests defined MCI and to study other cognitive deficits ill MC[. Method: Of 166 referrals with mild memory complaints, 124 non- demented, non-depressed cases were recruited into the Cambridge MC[ study. MCI was diagnosed by verbal memory based Petersen's criteria and further broadened to include performance on visual memory tests. Cognitive deficits beyond memory were studied ill the cohort. Results: Sevellty-two subjects fulfilled Petersell's criteria and all additional 18 were categorised as MCI on including performance on visual memory tests. Of 90 MCI subjects, 55 had impairment on more than one memory test. The majority (164/90), were found to have other cognitive deficits: semantic memory (ii -- 24), attelltiollal-execative function (11 - 22), visuospatial (ii _ 5) and three or more cognitive domains (n -- 13), Multiple domain involvement was more frequent among patients with both verbal and visual memory impairment. Twelve had non-amnesric cognitive impairment. Conclusion: Ill tiffs large study, Petersell's criteria showed good applicability ill clinical practice. The actual llmllber categorized as MC[ varied depending upon the number of memory tests used and modality of memory tested. Cognitive deficits beyond episodic memory were demonstrated in majority of amnestic MCI subjects and the pattern of cognitive deficits resembled heterogeneity observed in early AD.

0698 Widening the spectrum of Alzheimar's disease: Evidence from a large dinieopathologieal series of typical and atypical cases

Alladi S x, Knibb j 2 Xuereb JH 2, Hodges JR 2. ZNizam's Institute of Medical Sciences, Hyderabad, India," 2UnDersity of Cambridge, Cambridge, United Kingdom

Background: Alzheimer's disease (AD) is typically regarded as an amllestic sylldrome. However, scattered reports of lloll-amllestic presentations of AD exist. Prominent amnesia ill IIoli-AD dementias has also been described. Pathological verification of clinically typical and atypical AD is limited. In a large clinicopathological series, we determined pathology in typical AD presentations and also studied clinical presentations of classic AD pathology. Method: Of 166 consecutive cases studied ill the Cambridge Brain Bank, 47 had either a clinical diagnosis ill life or a pathological diagnosis of AD. Neuropsychological, imaging and lleuropathological data were reviewed. Clinically typical and atypical AD cases were identified and groups compared for initial cognitive profile, evolution, survival and pathology. Results: Of 19 clinically typical AD, 18 had pathologically confirmed AD and one frolltotemporal dementia pathology. Of 46 with AD pathology, 18 had clinically typical and 28 had atypical AD. Progressive aphasia was the most common atypical subtype (nonfluent aphasia 0 a -- equals; 8), mixed (n -- 1), fluent (n - 2) and semantic dementia 0 a -- 2)), followed by posterior cortical atrophy (PCA, n - 7),

$278 Wednesday, November 9, 2005 Poster Abstracts

Frontal variant (in -- 3), eorticobasal syndrome (CBS, n -- 3) and unusual motor presentations 0 a - 2). The range of clinical, imaging features and evolution are described. Overlap in cognitive profile was sigrdficant between PCA and CBS but between Frontal variant and PCA was minimal. Longitudinal data suggested that progressive aphasia tends to remain focal more titan variants. Conclusion: In this large neuropathological series, we have shown that clinical diagnosis of typical AD is most often confirmed by AD pathology. In contrast, AD pathology is associated with wide range of clinical presentations that have distinct cognitive profiles and evolution.

O699 The effect of L-glutamie acid and Norharman on brotizolam induced anterograde and retrograde amnesia in mice using Morris water umze task

Akshay A, Mattish K, Saraf, S. Prabhakar. Department of Neurology', Post Graduate Institute of Medical Education and Research, See-12 Chandigarh I60012 India

Background: The anterograde amnesia is an impairment to store new memories, where as retrograde amnesia includes the failure to retrieve old memories. Benzodiazepines such as diazepam, lorazepanl, are reported to produce attterograde amnesia but it does not affect retrieval mechanism. Triazolobenzodiazepine such as alprazolam, triazolam and brotizolam produces both anterograde and retrograde amnesia. Methods: The present study was designed to investigate the effect of norharman (benzodiazepine receptor inverse agonJst) and L-glutamic acid (glutamate receptor agonJst) on brotizolam induced anterograde and retrograde amnesia using Morris water maze task in mice. Results: Norharman reversed anterograde amnesia induced by brotizolam and did not reverse retrograde amnesia induced by it. L-glutanfic acid attenuated retrograde amnesia but did not affect anterograde anntesia induced by brotizolant. Conclusion: These results suggest that brotizolam induced atttero- grade amnesia may be mediated through activation of benzodiazepine receptor. These findings also lend support to our previous findings that retrograde amnesia may be mediated through PAF receptor.

0700 Tile intelrneulrons of tile cerebellmn in Vascular dementia

Baloyanais S z, Costa V 1. 2[st Department of Neurology, Aristotelian University, Thessaloniki, Greece

The interneurons of the cerebellar cortex play an important role in controlling the activity of Purkinje cells, interacting between mossy fibers, climbing fibers, parallel fibers and Purkinje cell dendritic spines cell body and axonic collaterals. The activity of the interneu- rons has a profound impact on the harmonious coordination of the cerebellar function. In the present study we attempted to describe the morphological and morphometric alterations of the cerebellar inter- neurons and their synapses with the Purkinje cells in vascular dementia, applying silver impregnation techlfiques and electron microscopy. A marked loss of the stellate and basket cells of the cerebellum was noticed in the vennis and the cerebellar hemispheres resulting to marked decrease of the synapses with the spines of the Purkinje cell dendrites. Morphological alterations of the organelles were noticed in stellate cell axonic terminals and in Purkinje cell dendritic spines. The presynaptic temrinals demonstrated marked polymorphism of synaptic vesicles, large mitochondria and multi- vesicular bodies. The Purkinje cell dendrites demonstrated low density of spines in the majority of the secondary and tertiary dendritic. branches. Most of the spines were dilated containing large mitochon- dria, multivesicular bodies and abnormal spinal apparatus. In addition mild astrocytic proliferation and increase of the astrocytic processes in the neuropial space was seen. The decrease of the syItaptic density

between the interneurons and the Purkinje cells may interpret the mild instability and dysarthria of a proportion of the patients suffered from vascular dementia.

0701 Cajal-Retzius cells in the acoustic cortex in early eases of Alzheimer's disease: A Golgi and Electron Microscope study

BMoyannis S t, Costa V ~. llS~ Department of Neurology, Aristotelian University, Thessaloniki, Greece

Alzheimers disease, is a neurodegenerative disorder of presenium and senimn, causing progressive decline of intellectual faculties, loss of professional skills, gradual impairment of behavior and social performance, associated with early loss of insight, impairment of COmmunication and speech eloquence and various neurological manifestations. Complex deficits of auditory functions are prominent in many patients. In previous studies we described the synaptic alterations in acoustic cortex, medial geniculate bodies and inferior colliculi, in brains of early cases of Alzheimer's disease. In the present study we studied the morphological and morphometric alterations of Cajal-Retzius cells in the layer I of acoustic cortex, since that cell, secreting reelin, plays a crucial role in cellular development and neuronal circuit formation. We examined twenty brains of early cases of Alzheimer's disease. For light microscopy we applied Golgi techniques, Golgi-Nissl, Holzer's, Bielschowsky-Hirano methods and Bodian impregnation technique. For electron microscopy the speci- mens were fixed in Sotelo's solution. The morphological study revealed alterations of the organelles of Cajal-Retzius cells, such as mitochon- drial alterations, fragmentation of the cisternae of the Golgi apparatus and synaptic alterations. The morphometric estimation revealed a dramatic decline of the number of Cajal-Retzius cells, in comparison with normal controls. Contusions: Since Cajal-Retzius cells and reelin are important factors for the synaptogenesis and the formation of local neuronal circuits, their loss may be implicated in the synaptic pathology and the multifactorious pathogenetic pathways of Alzheimer's disease, as well as in the impairment of central auditory function, which occurs frequently, even in early cases.

0702 Acetylcholinesterase inhibito~s in tile lreatnlent of patients with Alzheimer's disease and associated seizure disorders who maintain an antieonvulsant drug therapeutic level

Barrera, JC, Baccoli, M J, Jones, SM. Neurology/Clinical Neurophysiology, Mercy Hospital~Moses Taylor Hospital/Temple University, Scranton, PA, USA

Objective: To demonstrate that acetylcholinesterase (ACHE) inlfibitors interact with antiepileptic drugs (AED) jeopardizing effective control of seizures in patients with Alzheimer's disease. Background: AChE inhibitors are known to lower the seizure threshold in patients suffering from Alzheimer's disease and associated epileptic seizures. Methods: In a retrospective study, patients were selected if they fulfilled the NINCDS-ADRDA criteria for Alzheimer's disease and if associated clinical seizures were confirmed by electroencephalo- gram (EEG) in patients who had sinmltaneous treatment with AChE intfibitors and antiepileptic drugs which were maintained within therapeutic range. Results: From June 12, 2000 to January 21, 2005, fifteen patients fulfilled the selection criteria. There were three male and twelve female patients. Ages varied from 52 to 86 years. Six patients had complex partial seizures and nine patients had secondarily generalized tonic- clonic seizures. Nine patients were taking phenytoin, four patients were taking carbamazepine and two patients were taking valproic acid. Fourteen patients were taking donepezil and one patient was