- Email: [email protected]
THE RESEARCH LUMBAR PUNCTURE: FURTHER EVIDENCE OF SAFETY AND TOLERABILITY WHEN UNDERTAKEN BY EXPERIENCED ANAESTHETISTS
P884
Poster Presentations: P4
data obtained using commercially available single or multi-analyte immunoassay systems. Conclusions: In conclusion, the new EvalutionÔ platform provides great flexibility and simplicity for biomarker measurements in various biological fluids providing more answers much faster, with less effort and higher accuracy. The combination of the tools and the technology can become a step forward in biomarker use for the AD community. P4-272
THE RESEARCH LUMBAR PUNCTURE: FURTHER EVIDENCE OF SAFETY AND TOLERABILITY WHEN UNDERTAKEN BY EXPERIENCED ANAESTHETISTS
Fraser Inglis, Malcolm Sim, Kenny Lamb, Jennifer Lynch, Glasgow Memory Clinic Ltd, Glasgow, United Kingdom. Contact e-mail: fraser. [email protected] Background: The lumbar puncture was described in 1891 by Heinrich Quincke. Its use as a diagnostic aid in the ill patient with central nervous system pathology is well established. Its role as a research tool has a shorter history. With the advent of cerebrospinal fluid biomarkers, the research lumbar puncture is being undertaken more frequently to investigate a variety of conditions. Previous large series show a wide variation in the incidence of complications. In one, the authors report any adverse event as 11.7% and clinically significant adverse events as 3.97%. We have already shown that if undertaken by clinicians experienced in regional anaesthesia the rate of complications is considerably lower. We now describe additional data from our series as further evidence of this theory. Methods: In an audit of our practice, we analysed notes of 120 consecutive patients who underwent a lumbar puncture at the Glasgow Memory Clinic between October 2011 and May 2014. They were volunteers having cerebrospinal fluid biomarker analysis as part of commercial studies. All were mildly cognitively impaired or had probable mild Alzheimer’s disease. The procedures were carried out two experienced consultant anaesthetists who regularly perform spinal anaesthesia as part of their routine clinical practice. Results: Data was available for 118/120 patients (50 female, 68 male). Mean age 68.6 years. 102/118(86.4%) of procedures were completed at the first attempt, 14 (11.9%) on the second and 2 (1.7%) on the third. 3 patients (2.5%) complained of procedural back pain and 1 (0.8%) of back and leg pain. 2 (1.7%) had transient lower limb paraesthesiae. There were no bloody taps. Conclusions: The procedures were well tolerated with a very small percentage of transient symptoms. In the hands experienced anaesthetists using relatively narrow gauge spinal needles the Research Lumbar Puncture has a very low rate of immediate complications.
P4-273
patients with clinical follow-up of 361 years. During follow-up 17 MCI patients progressed to AD (MCI-AD), and 23 remained stable (sMCI). CSF neurogranin was measured by a novel in-house developed ELISA. We assessed d ifferences between groups using ANOVAs. The association of neurogranin with the CSF biomarkers amyloid-b 1-42 (Ab42), total tau and phosphorylated tau (p-tau) was assessed with linear regression analysis, adjusted for age and sex. We assessed predictive value of neurogranin for conversion from MCI to AD with age- and sex-adjusted Cox proportional hazards models. Results: Neurogranin levels were higher in AD patients compared to controls (3846267 vs. 115667 pg/mL; p<0.001). Moreover, MCI-AD patients had higher levels compared to sMCI patients (4376233 vs. 1786196 pg/mL; p<0.001) and controls (p<0.001). Neurogranin was associated with CSF tau and p-tau in MCI patients (St.B 1.16 [p<0.001] and 1.05 [p<0.001]) and AD patients (St.B 0.70 [p<0.001] and 0.83 [p<0.001]), but not in controls (St.B 0.58 [p¼0.41] and 0.73 [p¼0.17]). In addition, neurogranin (dichotomized at the median value of AD and controls) predicted conversion from MCI to dementia due to AD (HR[95% CI] 11.0[1.4-85.6], p¼0.02), as shown in the figure. Conclusions: In this study we confirmed and extended results from a previous pilot study in a larger, well-characterized clinical cohort. CSF neurogranin was elevated in MCIAD and AD patients, correlated with CSF markers of neuronal damage in these patients, and predicted conversion from MCI to dementia due to AD. These results suggest that neurogranin may be a sensitive prognostic marker, and may be useful in addition to the established AD CSF biomarkers.
CEREBROSPINAL FLUID NEUROGRANIN AS A PROGNOSTIC MARKER IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE
Flora H. Duits1, Hlin Johansson-Schmidt2, Erik Portelius2, Kerstin Andersson3, Ulf Andreasson4, Charlotte Teunissen5, Philip Scheltens6, Wiesje M. van der Flier1, Henrik Zetterberg7, Kaj Blennow7, 1VU University Medical Center, Amsterdam, Netherlands; 2 Sahlgrenska University Hospital, M€olndal, Sweden; 3Sahlgrenska University Hospital, M€ olndal, Sweden; 4Clinical Neurochemistry Laboratory, M€ olndal, Sweden; 5VU University Medical Center, Amsterdam, Netherlands; 6VU University Medical Center, Amsterdam, Netherlands; 7 Sahlgrenska Academy, University of Gothenburg, M€olndal, Sweden. Contact e-mail: [email protected] Background: Synaptic dysfunction is thought to play a major role in early stages of Alzheimer’s disease (AD), and it may be more directly related to cognitive functioning. Neurogranin is a dendritic protein, involved in regulating synaptic activity. In this study we assessed cerebrospinal fluid (CSF) levels of neurogranin in a clinical cohort, with the aim to confirm results of a recent pilot study. Methods: We included patients from the memory clinic based Amsterdam Dementia Cohort. Forty patients with AD (19F/21M, age 6568 years) were matched for age and sex to 40 controls, and to 40 MCI
P4-274
ACTIVITY-DEPENDENT NEUROPROTECTIVE PROTEIN (ADNP): MARKING ALZHEIMER’S DISEASE AND SCHIZOPHRENIA
Illana Gozes1, Anna Malishkevich2, Judith Aharon-Peretz3, 1Tel Aviv University, Tel Aviv, Israel; 2Tel Aviv University, Tel Aviv, Israel; 3Technion, Israel Institute of Technology, Haifa, Israel. Contact e-mail: igozes@post. tau.ac.il Background: Activity-dependent neuroprotective protein (ADNP) is essential for brain formation, constituting part of the chromatin remodeling complex, SWI/SNF. Our recent findings associated ADNP with the autophagy, a process preserving the balance between synthesis, degradation and recycling of cellular components. The proteins, beclin1 and microtubule associated protein 1 light chain 3 (LC3) regulate the autophagy process. We showed that ADNP haploinsufficiency in mice, which results in Alzheimer’s disease (AD)-like tauopathy and cognitive dysfunction, exhibited reduced hippocampal beclin1. At the protein level, ADNP co-immunoprecipitated with LC3B suggesting a direct association with the autophagy process.
Poster Presentations: P4
data obtained using commercially available single or multi-analyte immunoassay systems. Conclusions: In conclusion, the new EvalutionÔ platform provides great flexibility and simplicity for biomarker measurements in various biological fluids providing more answers much faster, with less effort and higher accuracy. The combination of the tools and the technology can become a step forward in biomarker use for the AD community. P4-272
THE RESEARCH LUMBAR PUNCTURE: FURTHER EVIDENCE OF SAFETY AND TOLERABILITY WHEN UNDERTAKEN BY EXPERIENCED ANAESTHETISTS
Fraser Inglis, Malcolm Sim, Kenny Lamb, Jennifer Lynch, Glasgow Memory Clinic Ltd, Glasgow, United Kingdom. Contact e-mail: fraser. [email protected] Background: The lumbar puncture was described in 1891 by Heinrich Quincke. Its use as a diagnostic aid in the ill patient with central nervous system pathology is well established. Its role as a research tool has a shorter history. With the advent of cerebrospinal fluid biomarkers, the research lumbar puncture is being undertaken more frequently to investigate a variety of conditions. Previous large series show a wide variation in the incidence of complications. In one, the authors report any adverse event as 11.7% and clinically significant adverse events as 3.97%. We have already shown that if undertaken by clinicians experienced in regional anaesthesia the rate of complications is considerably lower. We now describe additional data from our series as further evidence of this theory. Methods: In an audit of our practice, we analysed notes of 120 consecutive patients who underwent a lumbar puncture at the Glasgow Memory Clinic between October 2011 and May 2014. They were volunteers having cerebrospinal fluid biomarker analysis as part of commercial studies. All were mildly cognitively impaired or had probable mild Alzheimer’s disease. The procedures were carried out two experienced consultant anaesthetists who regularly perform spinal anaesthesia as part of their routine clinical practice. Results: Data was available for 118/120 patients (50 female, 68 male). Mean age 68.6 years. 102/118(86.4%) of procedures were completed at the first attempt, 14 (11.9%) on the second and 2 (1.7%) on the third. 3 patients (2.5%) complained of procedural back pain and 1 (0.8%) of back and leg pain. 2 (1.7%) had transient lower limb paraesthesiae. There were no bloody taps. Conclusions: The procedures were well tolerated with a very small percentage of transient symptoms. In the hands experienced anaesthetists using relatively narrow gauge spinal needles the Research Lumbar Puncture has a very low rate of immediate complications.
P4-273
patients with clinical follow-up of 361 years. During follow-up 17 MCI patients progressed to AD (MCI-AD), and 23 remained stable (sMCI). CSF neurogranin was measured by a novel in-house developed ELISA. We assessed d ifferences between groups using ANOVAs. The association of neurogranin with the CSF biomarkers amyloid-b 1-42 (Ab42), total tau and phosphorylated tau (p-tau) was assessed with linear regression analysis, adjusted for age and sex. We assessed predictive value of neurogranin for conversion from MCI to AD with age- and sex-adjusted Cox proportional hazards models. Results: Neurogranin levels were higher in AD patients compared to controls (3846267 vs. 115667 pg/mL; p<0.001). Moreover, MCI-AD patients had higher levels compared to sMCI patients (4376233 vs. 1786196 pg/mL; p<0.001) and controls (p<0.001). Neurogranin was associated with CSF tau and p-tau in MCI patients (St.B 1.16 [p<0.001] and 1.05 [p<0.001]) and AD patients (St.B 0.70 [p<0.001] and 0.83 [p<0.001]), but not in controls (St.B 0.58 [p¼0.41] and 0.73 [p¼0.17]). In addition, neurogranin (dichotomized at the median value of AD and controls) predicted conversion from MCI to dementia due to AD (HR[95% CI] 11.0[1.4-85.6], p¼0.02), as shown in the figure. Conclusions: In this study we confirmed and extended results from a previous pilot study in a larger, well-characterized clinical cohort. CSF neurogranin was elevated in MCIAD and AD patients, correlated with CSF markers of neuronal damage in these patients, and predicted conversion from MCI to dementia due to AD. These results suggest that neurogranin may be a sensitive prognostic marker, and may be useful in addition to the established AD CSF biomarkers.
CEREBROSPINAL FLUID NEUROGRANIN AS A PROGNOSTIC MARKER IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE
Flora H. Duits1, Hlin Johansson-Schmidt2, Erik Portelius2, Kerstin Andersson3, Ulf Andreasson4, Charlotte Teunissen5, Philip Scheltens6, Wiesje M. van der Flier1, Henrik Zetterberg7, Kaj Blennow7, 1VU University Medical Center, Amsterdam, Netherlands; 2 Sahlgrenska University Hospital, M€olndal, Sweden; 3Sahlgrenska University Hospital, M€ olndal, Sweden; 4Clinical Neurochemistry Laboratory, M€ olndal, Sweden; 5VU University Medical Center, Amsterdam, Netherlands; 6VU University Medical Center, Amsterdam, Netherlands; 7 Sahlgrenska Academy, University of Gothenburg, M€olndal, Sweden. Contact e-mail: [email protected] Background: Synaptic dysfunction is thought to play a major role in early stages of Alzheimer’s disease (AD), and it may be more directly related to cognitive functioning. Neurogranin is a dendritic protein, involved in regulating synaptic activity. In this study we assessed cerebrospinal fluid (CSF) levels of neurogranin in a clinical cohort, with the aim to confirm results of a recent pilot study. Methods: We included patients from the memory clinic based Amsterdam Dementia Cohort. Forty patients with AD (19F/21M, age 6568 years) were matched for age and sex to 40 controls, and to 40 MCI
P4-274
ACTIVITY-DEPENDENT NEUROPROTECTIVE PROTEIN (ADNP): MARKING ALZHEIMER’S DISEASE AND SCHIZOPHRENIA
Illana Gozes1, Anna Malishkevich2, Judith Aharon-Peretz3, 1Tel Aviv University, Tel Aviv, Israel; 2Tel Aviv University, Tel Aviv, Israel; 3Technion, Israel Institute of Technology, Haifa, Israel. Contact e-mail: igozes@post. tau.ac.il Background: Activity-dependent neuroprotective protein (ADNP) is essential for brain formation, constituting part of the chromatin remodeling complex, SWI/SNF. Our recent findings associated ADNP with the autophagy, a process preserving the balance between synthesis, degradation and recycling of cellular components. The proteins, beclin1 and microtubule associated protein 1 light chain 3 (LC3) regulate the autophagy process. We showed that ADNP haploinsufficiency in mice, which results in Alzheimer’s disease (AD)-like tauopathy and cognitive dysfunction, exhibited reduced hippocampal beclin1. At the protein level, ADNP co-immunoprecipitated with LC3B suggesting a direct association with the autophagy process.