There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Stefan Teipel |
| Institution: | University of Rostock |
| Department: | Department of Psychosomatic Medicine |
| Country: | |
| Proposed Analysis: | Abstract In previous work we developed techniques to indirectly assess the structural integrity of the cholinergic basal forebrain (BF) in-vivo, based on cytoarchitectonic maps of cholinergic nuclei and deformation-based morphometry of magnetic resonance images (MRI) (Teipel et al., 2005, 2011; Grothe et al., 2010). Recently, we applied these techniques to a large open-source MRI dataset (http://www.oasis-brains.org/), covering healthy subjects across the whole adult age-range as well as patients with early stages of Alzheimer´s Disease (AD) (Grothe et al., 2011). The main findings of that study were that there is a strong negative effect of advanced age on BF volume and that early stages of AD lead to a further reduction of BF volume, over and above the effect of age alone. The increased vulnerability of the cholinergic BF to both normal age-related neurodegeneration and AD pathology was further confirmed using longitudinal MRI of healthy elderly subjects and patients with early stages of AD from the OASIS database (in preparation). However, post-mortem studies as well as more recent molecular imaging studies indicate that a considerable proportion of cognitively normal subjects of advanced age harbour AD pathology in the form of amyloid plaques and neurofibrillary tangles (Knopman et al., 2003; Ewers et al., 2011). Therefore it remains to be elucidated to which degree cerebral amyloid load as a surrogate marker of AD pathology may account for the disproportionate volume loss of the BF in non-demented subjects, including cognitively normal elderly subjects and patients with mild cognitive impairment. Thus, we plan to use the ADNI data to divide these groups of non-demented subjects into amyloid-positive and amyloid-negative subgroups, based on their baseline CSF Aβ or, if available, PET (PiB-PET in ADNI I, or AV-45 PET in ADNI II). Cross-sectional as well as longitudinal analysis including serial MRI scans of the same subjects would then be used to calculate BF atrophy rates, similar to the techniques employed in Grothe et al., 2011. Thus, we request access to the CSF data, amyloid PET scans, baseline, and serial MRI scans in ADNI I and ADNI II as well as neuropsychological and clinical data. Comparison of BF volume and longitudinal rates of atrophy between groups would allow for an estimation of the relative contribution of AD related amyloid pathology to age-related volume loss of the cholinergic BF in cognitively normal aging and early stages of AD dementia. References: Ewers M, Frisoni GB, Teipel SJ, Grinberg LT, Amaro E Jr, Heinsen H, Thompson PM, Hampel H. Staging Alzheimer's disease progression with multimodality neuroimaging. Prog Neurobiol. 2011 Jun 22. [Epub ahead of print] Grothe M, Zaborszky L, Atienza M, Gil-Neciga E, Rodriguez-Romero R, Teipel SJ, Amunts K, Suarez-Gonzalez A, Cantero JL. Reduction of basal forebrain cholinergic system parallels cognitive impairment in patients at high risk of developing Alzheimer's disease. Cereb Cortex. 2010 Jul;20(7):1685-95. Epub 2009 Nov 4. Grothe M, Heinsen H, Teipel SJ. Atrophy of the Cholinergic Basal Forebrain Over the Adult Age Range and in Early Stages of Alzheimer's Disease. Biol Psychiatry. 2011 Aug 3. [Epub ahead of print] Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, Smith GE, Dickson DW, Johnson KA, Petersen LE, McDonald WC, Braak H, Petersen RC. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003 Nov;62(11):1087-95. Teipel SJ, Meindl T, Grinberg L, Grothe M, Cantero JL, Reiser MF, Möller HJ, Heinsen H, Hampel H. The cholinergic system in mild cognitive impairment and Alzheimer's disease: an in vivo MRI and DTI study. Hum Brain Mapp. 2011 Sep;32(9):1349-62. doi: 10.1002/ hbm.21111. Epub 2010 Jul 29. Teipel SJ, Flatz WH, Heinsen H, Bokde AL, Schoenberg SO, Stöckel S, Dietrich O, Reiser MF, Möller HJ, Hampel H. Measurement of basal forebrain atrophy in Alzheimer's disease using MRI. Brain. 2005 Nov;128(Pt 11):2626-44. Epub 2005 Jul 13. |
| Additional Investigators | |
| Investigator's Name: | Michel Grothe |
| Proposed Analysis: | Abstract In previous work we developed techniques to indirectly assess the structural integrity of the cholinergic basal forebrain (BF) in-vivo, based on cytoarchitectonic maps of cholinergic nuclei and deformation-based morphometry of magnetic resonance images (MRI) (Teipel et al., 2005, 2011; Grothe et al., 2010). Recently, we applied these techniques to a large open-source MRI dataset (http://www.oasis-brains.org/), covering healthy subjects across the whole adult age-range as well as patients with early stages of Alzheimer´s Disease (AD) (Grothe et al., 2011). The main findings of that study were that there is a strong negative effect of advanced age on BF volume and that early stages of AD lead to a further reduction of BF volume, over and above the effect of age alone. The increased vulnerability of the cholinergic BF to both normal age-related neurodegeneration and AD pathology was further confirmed using longitudinal MRI of healthy elderly subjects and patients with early stages of AD from the OASIS database (in preparation). However, post-mortem studies as well as more recent molecular imaging studies indicate that a considerable proportion of cognitively normal subjects of advanced age harbour AD pathology in the form of amyloid plaques and neurofibrillary tangles (Knopman et al., 2003; Ewers et al., 2011). Therefore it remains to be elucidated to which degree cerebral amyloid load as a surrogate marker of AD pathology may account for the disproportionate volume loss of the BF in non-demented subjects, including cognitively normal elderly subjects and patients with mild cognitive impairment. Thus, we plan to use the ADNI data to divide these groups of non-demented subjects into amyloid-positive and amyloid-negative subgroups, based on their baseline CSF Aβ or, if available, PET (PiB-PET in ADNI I, or AV-45 PET in ADNI II). Cross-sectional as well as longitudinal analysis including serial MRI scans of the same subjects would then be used to calculate BF atrophy rates, similar to the techniques employed in Grothe et al., 2011. Thus, we request access to the CSF data, amyloid PET scans, baseline, and serial MRI scans in ADNI I and ADNI II as well as neuropsychological and clinical data. Comparison of BF volume and longitudinal rates of atrophy between groups would allow for an estimation of the relative contribution of AD related amyloid pathology to age-related volume loss of the cholinergic BF in cognitively normal aging and early stages of AD dementia. References: Ewers M, Frisoni GB, Teipel SJ, Grinberg LT, Amaro E Jr, Heinsen H, Thompson PM, Hampel H. Staging Alzheimer's disease progression with multimodality neuroimaging. Prog Neurobiol. 2011 Jun 22. [Epub ahead of print] Grothe M, Zaborszky L, Atienza M, Gil-Neciga E, Rodriguez-Romero R, Teipel SJ, Amunts K, Suarez-Gonzalez A, Cantero JL. Reduction of basal forebrain cholinergic system parallels cognitive impairment in patients at high risk of developing Alzheimer's disease. Cereb Cortex. 2010 Jul;20(7):1685-95. Epub 2009 Nov 4. Grothe M, Heinsen H, Teipel SJ. Atrophy of the Cholinergic Basal Forebrain Over the Adult Age Range and in Early Stages of Alzheimer's Disease. Biol Psychiatry. 2011 Aug 3. [Epub ahead of print] Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, Smith GE, Dickson DW, Johnson KA, Petersen LE, McDonald WC, Braak H, Petersen RC. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003 Nov;62(11):1087-95. Teipel SJ, Meindl T, Grinberg L, Grothe M, Cantero JL, Reiser MF, Möller HJ, Heinsen H, Hampel H. The cholinergic system in mild cognitive impairment and Alzheimer's disease: an in vivo MRI and DTI study. Hum Brain Mapp. 2011 Sep;32(9):1349-62. doi: 10.1002/ hbm.21111. Epub 2010 Jul 29. Teipel SJ, Flatz WH, Heinsen H, Bokde AL, Schoenberg SO, Stöckel S, Dietrich O, Reiser MF, Möller HJ, Hampel H. Measurement of basal forebrain atrophy in Alzheimer's disease using MRI. Brain. 2005 Nov;128(Pt 11):2626-44. Epub 2005 Jul 13. |
