Abstract Details

Title Longitudinal Cognitive Performance and Cerebrospinal Fluid Biomarkers in Sporadic and Hereditary Frontotemporal Lobar Degeneration

Topic Aging and Dementia

Presentation(s) P05 - (-)

Poster/Presentation
Number 102

Objective

Background 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 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 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 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.

Authors/Disclosures
David Irwin, MD (University of Pennsylvania) PRESENTER	The institution of Dr. Irwin has received research support from NIH. The institution of Dr. Irwin has received research support from Prevail. The institution of Dr. Irwin has received research support from Passage Bio. The institution of Dr. Irwin has received research support from Alector. The institution of Dr. Irwin has received research support from Transposon. The institution of Dr. Irwin has received research support from Denali. The institution of Dr. Irwin has received research support from Cervo Med.
Danielle Weinberg	No disclosure on file
Corey McMillan, PhD (University of Pennsylvania)	Dr. McMillan has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. McMillan has received research support from Biogen. The institution of Dr. McMillan has received research support from NIH.
Jon B. Toledo	No disclosure on file
Steven E. Arnold, MD (Massachusetts General Hospital)	Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EIP Pharma. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sage Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cortexyme. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Boyle Shaughnessy Law. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Wolf Greenfield. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board Member with Bob's Last Marathon.
	No disclosure on file
Virginia Lee, PhD (University of Pennsylvania)	Virginia Lee, PhD has nothing to disclose.
John Q. Trojanowski, MD, PhD (University of PA School of Med)	Dr. Trojanowski has nothing to disclose.
Murray Grossman, MD, FAAN (University of Pennsylvania)	Dr. Grossman has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. The institution of Dr. Grossman has received research support from NIH.
Brett M. Kissela, MD, MS, FAAN (University of Cincinnati Hospital)	The institution of Dr. Kissela has received research support from NIH/NINDS. Dr. Kissela has a non-compensated relationship as a Board Member with AHA Regional Board that is relevant to AAN interests or activities.

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