[P05.102] Longitudinal Cognitive Performance and Cerebrospinal Fluid Biomarkers in Sporadic and Hereditary Frontotemporal Lobar Degeneration

David Irwin, Philadelphia, PA, Danielle Weinberg, Philadelphia, PA, Corey McMillan, Philadelphia, PA, Jon Toledo, Philadelphia, PA, Steven Arnold, Philadelphia, PA, Les M. Shaw, Philadelphia, PA, Virginia M. Y. Lee, Philadelphia, PA, John Trojanowski, Philadelphia, PA, Murray Grossman, Philadelphia, PA

OBJECTIVE: To compare longitudinal cognitive performance and cerebrospinal fluid (CSF) biomarkers in hereditary and sporadic forms of frontotemporal lobar degeneration (FTLD). BACKGROUND: Clinical trials of disease-modifying therapies in FTLD will require careful patient selection for homogeneous samples. While hereditary cases provide a useful surrogate for underlying neuropathology (i.e. tau or TDP-43), differences in rates of progression or biomarker profiles relative to sporadic cases could influence trial outcomes. DESIGN/METHODS: 26 autopsy-confirmed (FTLD-TDP=12, FTLD-Tau=14) and 27 hereditary FTLD cases (C9orf72=12, GRN=10, MAPT=5) with available neuropsychological testing within 3 months of CSF collection were studied. Follow-up testing obtained between 9 and 20 months after baseline assessment were used for longitudinal analysis (n=19 sporadic;n=11 hereditary). RESULTS: Groups did not differ in education, gender, APOE genotype or MAPT haplotype, onset-CSF collection interval, CSF collection-baseline cognitive assessment interval and interval between cognitive assessments (p>0.05). Mean CSF phosphorylated-tau (ptau) level (pg/ml) was higher in hereditary FTLD (12.2) than sporadic cases (10.5; MWU=236,p=0.04). Annualized-decline for Mini-mental status (t=2.12,p=0.04) and category fluency (t=2.19,p=0.08) was greater in hereditary (7.9 points/year;5.5 words/year) than sporadic cases (2.4 points/year; 1.5 words/year). Repeated-measure ANOVAs found significant interactions of hereditary status with MMSE (F(1,28)=4.5, p=0.04) and with category fluency (F(1,24)=4.23, p=0.05) scores between visits, suggesting more rapid decline on these measures for hereditary than sporadic FTLD. CONCLUSIONS: Hereditary forms of FTLD may have more rapid cognitive decline and differing CSF ptau profile compared with sporadic cases that could influence clinical trial outcome measures. Due to the large hereditary component of FTLD, careful consideration of study populations will be necessary. These results will require confirmation in larger samples sufficient for comparison between specific genetic and neuropathological FTLD subtypes. Supported by: Grants: P30AG010124-20, P01 AG017586, R01 NS44266, R01 AG15116, P01 AG32953, and P01 NS53488 from the National Institutes of Health and grants from the Wyncote Foundation. Dr Irwin's work is supported by training grant T32-AG000255 from the National Institutes of Health, and Dr Toledo's work is supported by a grant from the Alfonso Marti´n Escudero Foundation.
Category - Aging and Dementia: Other

Wednesday, March 20, 2013 2:00 PM

Session P05: Frontotemporal Lobar Degeneration: Genetics, Pathology, and Imaging (2:00 PM-7:00 PM)