Abstract Details

Title Aggregation of Neurodegenerative and Neuropsychiatric Illness in ALS Kindreds

Topic Anterior Horn

Presentation(s) P07 - (-)

Poster/Presentation
Number 062

Objective

Background BACKGROUND: There is clinical and genetic evidence of overlap between ALS and Frontotemporal Dementia (FTD). Aggregation of other neurodegenerative diseases in ALS kindreds has been reported. An expanded phenotoype has been described in some kindreds with hexanucleotide repeats in C9orf72, with a higher than expected frequency of psychosis. .

Design/Methods DESIGN/METHODS: 172 incident ALS cases and 192 matched controls completed a detailed questionnaire relating to medical conditions in all first- and second-degree relatives. Data were verified by interview with another family member and by death certification. Data from 4,050 first- and second-degree relatives of 172 cases and 5,634 first- and second-degree relatives of 192 controls were analysed. Estimated Hazard rates and 95% confidence intervals were calculated using Cox proportional models . Statistical analysis was carried out by SPSS 16.

Results RESULTS: There was a higher relative risk of dementia (Hazard ratio =1.3) Schizophrenia (Hazard ratio =4.2) and suicide (hazard ratio 4.9) but not Parkinsons Disease in kindred of ALS patients. Subgroup analysis using Cox-proportional hazard analysis compared disease risk in i) 3,335 relatives of 155 ALS patients without the C9orf72 expansion, and ii) 401 relatives of 17 C9orf72 repeat expansion positive patients, with 5,634 relatives of 192 controls. In kindreds of those with C9orf72 expansion hazard ratios (compared to controls) were as follows; Dementia HR =1.6, Parkinsons HR=1.4, Depression HR =3.3, schizophrenia HR=18.2, Suicide HR=6.6. Elevated hazard ratios for schizophrenia (HR=4.7) and suicide (5.1) were also observed in ALS kindreds without expanded repeats in C9orf72.

Conclusions CONCLUSIONS: There is an increased aggregation of neuropsychiatric illness and suicide in kindreds of ALS patients. These findings suggest a biologic overlap between ALS and some forms of neuropsychiatric disease.

Authors/Disclosures
Susan C. Byrne, MD PRESENTER	No disclosure on file
	No disclosure on file
Marwa Elamin, MD, PhD (University College Hospital Galway)	Dr. Elamin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche .
Orla Hardiman, MD, DSc, FRCPI, MRIA, FAAN (Trinity Biomedical Sciences Institute)	Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Pharmaceuticals. Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cytokinetics . Dr. Hardiman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hardiman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Taylor and Francis. The institution of Dr. Hardiman has received research support from Science Foundation Ireland. The institution of Dr. Hardiman has received research support from HRB.
Lauren B. Krupp, MD, FAAN (NYU Langone Medical Center)	Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EBIX. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman LaRoche. Dr. krupp has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MMMK. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Patrick, Dolan, and Kaufman. Dr. krupp has received intellectual property interests from a discovery or technology relating to health care.

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