- Email: [email protected]
AN AMYLOID PET–POSITIVE SUBJECT WITH HIV AND DEMENTIA
Poster Presentations: Monday, July 25, 2016
single-centre cohort study. MOCA was performed in patients newly started on PD between July 2011 and July 2015 at Queen Mary Hospital, Hong Kong, and repeated one year later. Demographics and clinical data were collected. CI was determined by locally defined MOCA cut-off. Risk factors for CI were analyzed using univariate and multivariate logistic regression. Results: 137 patients were included, and 94 patients (69%) underwent the second MOCA assessment. The prevalence of CI at baseline and 1-year was 34% and 32% respectively. MOCA score was 2365.0 at baseline and 2366.0 after 1 year (p¼0.29). Forty-seven percent of patients showed deterioration in MOCA score. Diabetes mellitus, education level of primary school or below, and age greater than 65 years were associated with CI at 1-year after starting PD, but only the later remained a significant risk factor for CI in the multivariate model (OR 2.72, 95%CI 1.04-7.09, p¼0.04). Patients with CI at 1-year after starting PD had more frequent PD peritonitis (1 episode in 22 patient months, vs. 1 in 48 patient months in those without CI, p¼0.01). Also, their median length-of-stay for emergency hospitalizations was longer (4 days, IQR 0-10, vs. 0 day, IQR 0-4, p¼0.01). After excluding patients on helper-assisted PD, the rates of peritonitis and exit-site infection still appeared higher in those with CI although the difference did not reach statistical significance (1 episode in 27 and 18 patient months respectively, vs. 1 in 43 and 32 patient months in those without CI, p¼0.07 and 0.06 respectively). Conclusions: Age above 65 is an independent risk factor for CI at one year after commencement of PD, and the latter is associated with adverse clinical outcomes including more hospitalization, peritonitis and exit-site infection.
P2-182
A VARIANT OF FRONTOTEMPORAL LOBAR DEGENERATION WITH EXPANDED TRINUCLEOTIDE CAG REPEATS IN THE HUNTINGTIN GENE
Stanislav Sutovsky1, Peter Turcani1, Michal Novak2, Irina Alafuzoff3, Norbert Zilka2, 1Faculty of Medicine, Comenius University & University Hospital Bratislava, Bratislava, Slovakia; 2AXON Neuroscience SE, Bratislava, Slovakia; 3Uppsala University, Uppsala, Sweden. Contact e-mail: [email protected] Background: Frontotemporal lobar degeneration (FTLD) incorporates a group of aging related neurodegenerative disorders with heterogeneous clinical and neuropathological presentation. Methods: A 54-year-old female with history of 18 years progression of personality and behavioral changes such as fluctuation of apathy and euphoria, perseveration, bizarre affect, and general disengagement, preliminarily assessed as behavioral variant of FTLD has undergone a clinical and genetic examination and precise neuropathological analysis post mortem. Results: The clinical onset was at the age of 36 years and the disease progressed slowly (18 years). Genetic testing revealed expanded trinucleotide CAG repeat in the Huntingtin gene, together with a Glu318Gly polymorphism in presenilin 1. Neuropathological assessment revealed extensive amyloid b (Ab) aggregates in all cortical regions. No inclusions displaying hyperphosphorylated tau or phosphorylated transactive response DNA-binding protein 43 (TDP43) were found. A high number of p62 (sequestosome 1) immunopositive intranuclear inclusions were seen mainly in the cortex, while subcortical areas were affected to a lesser extent. The confocal microscopy revealed that the majority of p62 intranuclear lesions colocalized
P687
with the fused-in-sarcoma protein (FUS) immunostaining. The morphology of the inclusions resembled intranuclear aggregates in Huntington’s disease. Conclusions: Our data show for the first time that the bv-FTLD phenotype may be associated with the huntingtin (HTT) trinucleotide repeat expansion (CAG). This indicates that mutations in huntingtin might result in FTLD and thus should be included in the list of genes causative for familial forms of FTLD.
P2-183
AN AMYLOID PET–POSITIVE SUBJECT WITH HIV AND DEMENTIA
Raymond Scott Turner1, Melanie Chadwick1, Xiong Jiang2, Guiseppe Esposito1, 1Georgetown University, Washington, DC, USA; 2 Georgetown.University, Washington, DC, USA. Contact e-mail: rst36@ georgetown.edu Background: To date, no HIV+ individual has been reported to have a positive amyloid PET scan. HIV associated neurocognitive decline (HAND) occurs in more than half of treated HIV+ individuals. Methods: Case report. The subject was born in 1945. He was diagnosed with HIV in 2002 after a flu-like illness and viral pneumonia. Since then, he was consistently compliant with antiretroviral therapy and his 4-year progressive cognitive decline was presumed due to HAND. His mother had dementia due to probable AD. Results: Neuropsychologic evaluations confirmed a progressive mild dementia with deficits in attention, memory, language, visuospatial, and executive tasks. A brain MRI revealed atrophy and white matter changes consistent with age. FDG-PET revealed hypermetabolism in bilateral basal ganglia (consistent with HAND) and marked hypometabolism of parietal cortex including the posterior cingulate/precuneus (consistent with AD). Likewise, resting state fMRI revealed altered connectivity consistent with individuals with MCI/AD and with HIV+ cognitively intact subjects, especially the connectivity between the posterior cingulate cortex and other brain regions. CSF examination revealed conflicting results (a low Ab42/tau index consistent with AD but a low phospho-tau). An amyloid PET/CT with NeuraceqTM (florbetaben F18) revealed pronounced radiotracer deposition in the frontal, temporal, and parietal lobes bilaterally consistent with AD. ApoE genotype was not tested. Blood tests were unrevealing with the exception of a chronic subnormal CD4 T cell count. Conclusions: This case report suggests that progressive dementia in older HIV+ individuals may be due to HAND, AD, or both. CNS HIV infection does not preclude Ab/amyloid deposition. Amyloid PET neuroimaging may be of value in distinguishing HAND from HAND/AD in HIV+ individuals with progressive cognitive decline.
P2-184
AN AUTOMATED ELECTRONIC RATING SYSTEM FOR THE OVERLAPPED PENTAGONS IN DEMENTIA SCREENING TESTS
Kelvin K. F. Tsoi, Nelson W. Y. Leung, Max W. Y. Lam, The Chinese University of Hong Kong, Shatin, Hong Kong. Contact e-mail: kelvintsoi@ cuhk.edu.hk Background: Dementia is a globe public health problem among
the ageing population worldwide. There are many screening tests available for the early detection of dementia; most of them are paper-based and involve geometric drawing. Drawings
single-centre cohort study. MOCA was performed in patients newly started on PD between July 2011 and July 2015 at Queen Mary Hospital, Hong Kong, and repeated one year later. Demographics and clinical data were collected. CI was determined by locally defined MOCA cut-off. Risk factors for CI were analyzed using univariate and multivariate logistic regression. Results: 137 patients were included, and 94 patients (69%) underwent the second MOCA assessment. The prevalence of CI at baseline and 1-year was 34% and 32% respectively. MOCA score was 2365.0 at baseline and 2366.0 after 1 year (p¼0.29). Forty-seven percent of patients showed deterioration in MOCA score. Diabetes mellitus, education level of primary school or below, and age greater than 65 years were associated with CI at 1-year after starting PD, but only the later remained a significant risk factor for CI in the multivariate model (OR 2.72, 95%CI 1.04-7.09, p¼0.04). Patients with CI at 1-year after starting PD had more frequent PD peritonitis (1 episode in 22 patient months, vs. 1 in 48 patient months in those without CI, p¼0.01). Also, their median length-of-stay for emergency hospitalizations was longer (4 days, IQR 0-10, vs. 0 day, IQR 0-4, p¼0.01). After excluding patients on helper-assisted PD, the rates of peritonitis and exit-site infection still appeared higher in those with CI although the difference did not reach statistical significance (1 episode in 27 and 18 patient months respectively, vs. 1 in 43 and 32 patient months in those without CI, p¼0.07 and 0.06 respectively). Conclusions: Age above 65 is an independent risk factor for CI at one year after commencement of PD, and the latter is associated with adverse clinical outcomes including more hospitalization, peritonitis and exit-site infection.
P2-182
A VARIANT OF FRONTOTEMPORAL LOBAR DEGENERATION WITH EXPANDED TRINUCLEOTIDE CAG REPEATS IN THE HUNTINGTIN GENE
Stanislav Sutovsky1, Peter Turcani1, Michal Novak2, Irina Alafuzoff3, Norbert Zilka2, 1Faculty of Medicine, Comenius University & University Hospital Bratislava, Bratislava, Slovakia; 2AXON Neuroscience SE, Bratislava, Slovakia; 3Uppsala University, Uppsala, Sweden. Contact e-mail: [email protected] Background: Frontotemporal lobar degeneration (FTLD) incorporates a group of aging related neurodegenerative disorders with heterogeneous clinical and neuropathological presentation. Methods: A 54-year-old female with history of 18 years progression of personality and behavioral changes such as fluctuation of apathy and euphoria, perseveration, bizarre affect, and general disengagement, preliminarily assessed as behavioral variant of FTLD has undergone a clinical and genetic examination and precise neuropathological analysis post mortem. Results: The clinical onset was at the age of 36 years and the disease progressed slowly (18 years). Genetic testing revealed expanded trinucleotide CAG repeat in the Huntingtin gene, together with a Glu318Gly polymorphism in presenilin 1. Neuropathological assessment revealed extensive amyloid b (Ab) aggregates in all cortical regions. No inclusions displaying hyperphosphorylated tau or phosphorylated transactive response DNA-binding protein 43 (TDP43) were found. A high number of p62 (sequestosome 1) immunopositive intranuclear inclusions were seen mainly in the cortex, while subcortical areas were affected to a lesser extent. The confocal microscopy revealed that the majority of p62 intranuclear lesions colocalized
P687
with the fused-in-sarcoma protein (FUS) immunostaining. The morphology of the inclusions resembled intranuclear aggregates in Huntington’s disease. Conclusions: Our data show for the first time that the bv-FTLD phenotype may be associated with the huntingtin (HTT) trinucleotide repeat expansion (CAG). This indicates that mutations in huntingtin might result in FTLD and thus should be included in the list of genes causative for familial forms of FTLD.
P2-183
AN AMYLOID PET–POSITIVE SUBJECT WITH HIV AND DEMENTIA
Raymond Scott Turner1, Melanie Chadwick1, Xiong Jiang2, Guiseppe Esposito1, 1Georgetown University, Washington, DC, USA; 2 Georgetown.University, Washington, DC, USA. Contact e-mail: rst36@ georgetown.edu Background: To date, no HIV+ individual has been reported to have a positive amyloid PET scan. HIV associated neurocognitive decline (HAND) occurs in more than half of treated HIV+ individuals. Methods: Case report. The subject was born in 1945. He was diagnosed with HIV in 2002 after a flu-like illness and viral pneumonia. Since then, he was consistently compliant with antiretroviral therapy and his 4-year progressive cognitive decline was presumed due to HAND. His mother had dementia due to probable AD. Results: Neuropsychologic evaluations confirmed a progressive mild dementia with deficits in attention, memory, language, visuospatial, and executive tasks. A brain MRI revealed atrophy and white matter changes consistent with age. FDG-PET revealed hypermetabolism in bilateral basal ganglia (consistent with HAND) and marked hypometabolism of parietal cortex including the posterior cingulate/precuneus (consistent with AD). Likewise, resting state fMRI revealed altered connectivity consistent with individuals with MCI/AD and with HIV+ cognitively intact subjects, especially the connectivity between the posterior cingulate cortex and other brain regions. CSF examination revealed conflicting results (a low Ab42/tau index consistent with AD but a low phospho-tau). An amyloid PET/CT with NeuraceqTM (florbetaben F18) revealed pronounced radiotracer deposition in the frontal, temporal, and parietal lobes bilaterally consistent with AD. ApoE genotype was not tested. Blood tests were unrevealing with the exception of a chronic subnormal CD4 T cell count. Conclusions: This case report suggests that progressive dementia in older HIV+ individuals may be due to HAND, AD, or both. CNS HIV infection does not preclude Ab/amyloid deposition. Amyloid PET neuroimaging may be of value in distinguishing HAND from HAND/AD in HIV+ individuals with progressive cognitive decline.
P2-184
AN AUTOMATED ELECTRONIC RATING SYSTEM FOR THE OVERLAPPED PENTAGONS IN DEMENTIA SCREENING TESTS
Kelvin K. F. Tsoi, Nelson W. Y. Leung, Max W. Y. Lam, The Chinese University of Hong Kong, Shatin, Hong Kong. Contact e-mail: kelvintsoi@ cuhk.edu.hk Background: Dementia is a globe public health problem among
the ageing population worldwide. There are many screening tests available for the early detection of dementia; most of them are paper-based and involve geometric drawing. Drawings