TY - JOUR

T1 - Cognitive impairment in the preclinical stage of dementia in FTD-3 CHMP2B mutation carriers

T2 - A longitudinal prospective study

AU - Stokholm, Jette

AU - Teasdale, Thomas W

AU - Johannsen, Peter

AU - Nielsen, Jorgen E

AU - Nielsen, Troels Tolstrup

AU - Isaacs, Adrian

AU - Brown, Jerry M

AU - Gade, Anders

AU - and the Frontotemporal dementia Research in Jutland Association (FReJA) consortium

PY - 2013/2

Y1 - 2013/2

N2 - OBJECTIVE AND METHODS: A longitudinal study spanning over 8 years and including 17 asymptomatic individuals with CHMP2B mutations was conducted to assess the earliest neuropsychological changes in autosomal dominant neurodegenerative disease frontotemporal dementia (FTD) linked to chromosome 3 (FTD-3). Subjects were assessed with neuropsychological tests in 2002, 2005 and 2010. RESULTS: Cross-sectional analyses showed that the mutation carriers scored lower on tests of psychomotor speed, working memory, executive functions and verbal memory than a control group consisting of not-at-risk family members and spouses. Longitudinal analyses showed a gradual decline in psychomotor speed, working memory capacity and global executive measures in the group of non-demented mutation carriers that was not found in the control group. In contrast, there were no significant group differences in domain scores on memory or visuospatial functions. On an individual level the cognitive changes over time varied considerably. CONCLUSION: Subjects with CHMP2B mutation show cognitive changes dominated by executive dysfunctions, years before they fulfil diagnostic criteria of FTD. However, there is great heterogeneity in the individual cognitive trajectories.

AB - OBJECTIVE AND METHODS: A longitudinal study spanning over 8 years and including 17 asymptomatic individuals with CHMP2B mutations was conducted to assess the earliest neuropsychological changes in autosomal dominant neurodegenerative disease frontotemporal dementia (FTD) linked to chromosome 3 (FTD-3). Subjects were assessed with neuropsychological tests in 2002, 2005 and 2010. RESULTS: Cross-sectional analyses showed that the mutation carriers scored lower on tests of psychomotor speed, working memory, executive functions and verbal memory than a control group consisting of not-at-risk family members and spouses. Longitudinal analyses showed a gradual decline in psychomotor speed, working memory capacity and global executive measures in the group of non-demented mutation carriers that was not found in the control group. In contrast, there were no significant group differences in domain scores on memory or visuospatial functions. On an individual level the cognitive changes over time varied considerably. CONCLUSION: Subjects with CHMP2B mutation show cognitive changes dominated by executive dysfunctions, years before they fulfil diagnostic criteria of FTD. However, there is great heterogeneity in the individual cognitive trajectories.

U2 - 10.1136/jnnp-2012-303813

DO - 10.1136/jnnp-2012-303813

M3 - Journal article

C2 - 23142962

VL - 84

SP - 170

EP - 176

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

IS - 2

ER -