Neuropsychological functions in variant Alzheimer’s disease with spastic paraparesis Auli Verkkoniemi a,b, * , Raija Ylikoski a , Juha O. Rinne c , Mirja Somer d , Aki Hietaharju e , Timo Erkinjuntti a , Matti Viitanen f,g , Hannu Kalimo h,i , Matti Haltia b a Department of Clinical Neurosciences, Helsinki University Central Hospital, Helsinki FIN-00290, Finland b Department of Pathology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland c The Turku PET Center, Turku University Hospital, Turku FIN-20520, Finland d The Family Federation of Finland, PO Box 849, Helsinki FIN-00101, Finland e Department of Neurology, Tampere University Hospital, Tampere FIN-33520, Finland f Division of Geriatric Medicine, Karolinska Institutet, Huddinge Hospital, Huddinge SE-14186, Sweden g University of Turku, Turku FIN-20520, Finland h Department of Genetics and Pathology, University of Uppsala, Uppsala SE-75185, Sweden i Department of Pathology, Turku University Hospital, Turku FIN-20520, Finland Received 20 February 2003; received in revised form 10 October 2003; accepted 14 October 2003 Abstract Few data exist on the effects of specific Alzheimer’s disease (AD)-related mutations on cognitive function. We present neuropsychological test results in eight members of a large kindred with variant Alzheimer’s disease (VarAD) due to a deletion of the presenilin 1 (PS-1) gene, encompassing exon 9. The disease was neuropathologically characterized by the presence of large, unusual, ‘‘cotton wool’’ plaques (CWP). Four surviving patients were prospectively tested, and retrospective neuropsychological data were collected from additional four deceased patients. The neuropsychological evaluation was based on tests of verbal and visual memory, abstract thinking, and visuoconstructive and spatial functions. In addition, psychiatric symptoms were evaluated. In four patients, brain glucose metabolism was examined by positron emission tomography (PET). PET showed temporoparietal hypometabolism typical of AD. In addition, variable patterns of hypometabolism (hemispherical asymmetry and occipital accentuation) were related to individual deficits of cognitive performance. However, all these early- onset patients (age range 43 – 63 years) with a deletion mutation of PS-1 gene showed prominent memory impairment and deficits in visuoconstructive and intellectual functions. D 2003 Elsevier B.V. All rights reserved. Keywords: Variant AD; Visuoconstructive defects; Spastic paraparesis; PET 1. Introduction Neuropsychological assessment has gained considerable importance in evaluating both clinical and preclinical stages of probable Alzheimer’s disease (AD) [1–4]. Memory deficits are cardinal features of sporadic and familial forms of the disease. AD generally manifests with impairment of episodic memory, related to damage in medial temporal regions, especially the hippocampal and perihippocampal structures [5]. The other important deficits are found in verbal abilities, attention, and visuospatial and executive functions [4]. Although the majority of AD cases are sporadic, about 5% of patients show a Mendelian pattern of inheritance [6]. Familial Alzheimer’s disease (FAD) is genetically hetero- geneous, and three genes have been shown to be involved in the etiology: amyloid precursor protein (APP) gene on chromosome 21 [7], presenilin 1 (PS-1) gene on chromo- some 14 [8–10], and presenilin 2 (PS-2) gene on chromo- some 1 [11,12]. In FAD, neuropsychological investigations have a special value in evaluating relatives at risk of inheriting AD [13] and presymptomatic mutation carriers after molecular genetic analysis [14]. However, for the time being, only a few studies with a limited number of patients 0022-510X/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2003.10.020 * Corresponding author. Department of Clinical Neurosciences, Helsinki University Central Hospital, Haartmaninkatu 4, Helsinki FIN- 00290, Finland. Tel.: +358-50-5218042; fax: +358-9-47174009. E-mail address: Auli@doctor.com (A. Verkkoniemi). www.elsevier.com/locate/jns Journal of the Neurological Sciences 218 (2004) 29 – 37