title: Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis).
abstract: Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuropsychological or psychiatric symptomatology we studied 35 AGel patients and 29 control subjects. Neuropsychological tests showed abnormalities in visuocontructional and -spatial performance in AGel patients, also some indication of problems in processing efficacy was found. At psychiatric evaluation the patient group showed more psychiatric symptomatology, mainly depression. In brain MRI, available in 16 patients and 14 controls, we found microhemorrhages or microcalcifications only in the patient group, although the number of findings was small. Our study shows that AGel amyloidosis can be associated with visuoconstructional problems and depression, but severe neuropsychiatric involvement is not characteristic. The gelsolin mutation may even induce cerebrovascular fragility, but further epidemiological and histopathological as well as longitudinal follow-up studies are needed to clarify gelsolin-related vascular pathology and its clinical consequences.
authors.affiliation: Helsinki University Central Hospital (HUCH), Department of Psychiatry , Hospital District of Helsinki and Uusimaa , Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Kantanen
authors.affiliation: Helsinki University Central Hospital (HUCH), Department of Neurology , Hospital District of Helsinki and Uusimaa , Finland ; Department of Clinical Neurosciences, University of Helsinki , Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Kiuru-Enari
authors.affiliation: Helsinki University Central Hospital (HUCH), Department of Radiology , Hospital District of Helsinki and Uusimaa , Finland.
authors.forename: Oili
authors.initials: O
authors.lastname: Salonen
authors.affiliation: Helsinki University Central Hospital (HUCH), Department of Psychiatry , Hospital District of Helsinki and Uusimaa , Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Kaipainen
authors.affiliation: Institute of Behavioural Sciences, Division of Cognitive Psychology and Neuropsychology, University of Helsinki , Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Hokkanen
keywords: Depression; Gelsolin amyloidosis; Hereditary amyloidosis; Magnetic resonance imaging; Neuropsychological testing; Visuoconstructional problems
references.citation: Acta Neuropathol. 2009 Jul;118(1):115-30
references.pmid: 19225789
references.citation: Neuropathology. 2000 Mar;20(1):8-22
references.pmid: 10935432
references.citation: Acta Psychiatr Scand. 1998 Jan;97(1):42-6
references.pmid: 9504702
references.citation: Dialogues Clin Neurosci. 2007;9(2):141-51
references.pmid: 17726913
references.citation: Cerebrovasc Dis. 2012;33(5):430-5
references.pmid: 22456577
references.citation: Psychopharmacol Bull. 1973 Jan;9(1):13-28
references.pmid: 4682398
references.citation: Acta Neurol Scand. 2012 Jan;125(1):16-23
references.pmid: 21198445
references.citation: Ann Neurol. 2010 Dec;68(6):934-43
references.pmid: 21061402
references.citation: Stroke. 2004 Nov;35(11 Suppl 1):2616-9
references.pmid: 15459438
references.citation: J Affect Disord. 2005 Oct;88(2):155-62
references.pmid: 16098601
references.citation: Arch Gen Psychiatry. 2002 Sep;59(9):785-92
references.pmid: 12215077
references.citation: Genomics. 1992 May;13(1):237-9
references.pmid: 1315718
references.citation: Neurology. 2006 Jan 24;66(2):165-71
references.pmid: 16434647
references.citation: Ann Neurol. 1999 Mar;45(3):305-11
references.pmid: 10072044
references.citation: BMC Neurol. 2009 Jan 13;9:3
references.pmid: 19144113
references.citation: J Neurol Neurosurg Psychiatry. 2012 Feb;83(2):124-37
references.pmid: 22056963
references.citation: Ann Neurol. 2011 Feb;69(2):320-7
references.pmid: 21387377
references.citation: Dement Geriatr Cogn Disord. 2011;32(6):367-78
references.pmid: 22301385
references.citation: AJR Am J Roentgenol. 1987 Aug;149(2):351-6
references.pmid: 3496763
references.citation: Neurobiol Aging. 1991 Jul-Aug;12(4):313-6
references.pmid: 1660109
references.citation: Brain. 2004 Oct;127(Pt 10):2265-75
references.pmid: 15282216
references.citation: Percept Mot Skills. 1977 Apr;44(2):367-73
references.pmid: 866038
references.citation: Neurology. 2002 Jun 11;58(11):1629-34
references.pmid: 12058090
references.citation: Arch Neurol. 1993 Aug;50(8):873-80
references.pmid: 8352676
references.citation: Isr Med Assoc J. 2006 Nov;8(11):803-6
references.pmid: 17180835
references.citation: J Clin Psychol. 1987 Jul;43(4):402-9
references.pmid: 3611374
references.citation: Handb Clin Neurol. 2013;115:659-81
references.pmid: 23931809
references.citation: Neurology. 2012 Jan 31;78(5):326-33
references.pmid: 22262748
references.citation: Radiographics. 2006 Sep-Oct;26(5):1517-31
references.pmid: 16973779
references.citation: Acta Psychol (Amst). 1966;25(1):36-93
references.pmid: 5328883
references.citation: Neurology. 1986 Mar;36(3):432-5
references.pmid: 3513049
references.citation: Ann Clin Res. 1969 Dec;1(4):314-24
references.pmid: 4313418
references.citation: Brain. 1990 Oct;113 ( Pt 5):1251-67
references.pmid: 2245295
references.citation: Nord J Psychiatry. 2003;57(3):233-8
references.pmid: 12775300
references.citation: Lancet. 1992 Aug 22;340(8817):453-4
references.pmid: 1354785