Neuroscience
Diamond EL, Miller S, Dickerson BC, Atri A, Depeau K, Fenstermacher E, Pihlajamäki M, Celone K, Salisbury S, Gregas M, Rentz D, & Sperling RA. Relationship of fMRI activation to clinical trial memory measures in Alzheimer disease. Neurology. 2007 Sep 25; 69(13): 1331-1341.
Memory Disorders Unit, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115
BACKGROUND: Functional MRI (fMRI) has shown promise as a tool to characterize altered brain function in Alzheimer disease (AD) and for use in proof of concept clinical trials. FMRI studies of subjects with AD have demonstrated altered hippocampal and neocortical activation while encoding novel stimuli compared to older controls. However, the relationship between fMRI activation and performance on standardized clinical trial memory measures has not been fully investigated. OBJECTIVE: To determine whether patterns of activation during an associative-memory fMRI paradigm correlate with performance on memory measures used in AD clinical trials. METHODS: Twenty-nine subjects with AD underwent neuropsychological testing, including the AD Assessment Scale (ADAS-Cog), and an associative-encoding fMRI paradigm. Scores were entered as regressors in SPM2 analyses of the differential fMRI activation to novel-vs-repeated (NvR) stimuli. To account for cerebral atrophy, native-space structure-function analyses were performed with subjects' high-resolution structural images. RESULTS: Performance on the ADAS-Cog verbal memory component, and the ADAS-Cog total score, correlated with NvR activation in left superior temporal (p = 0.0003; r = -0.51) and left prefrontal (p = 0.00001; r = -0.63) cortices. In a subgroup with more extensive neuropsychological testing (n = 14), performance on the Free and Cued Selective Reminding Test was correlated with activation in these same regions. fMRI activation remained correlated with performance even when accounting for atrophy. CONCLUSIONS: The relationship between functional MRI (fMRI) activation and standardized memory measures supports the potential use of fMRI to investigate regional mechanisms of treatment response in clinical trials of novel therapies for Alzheimer disease. GLOSSARY: AD = Alzheimer disease; ADAS-Cog = AD Assessment Scale; EPI = echoplanar imaging sequence; FA = flip angle; FCSRT = Free and Cued Selective Reminding Test; FLAME = FMRIB's Local Analysis of Mixed Effects; fMRI = Functional MRI; FOV = field of view; GLM = general linear model; HRF = hemodynamic response function; LFG = left fusiform gyrus; LPFC = left prefrontal cortex; LSTG = left superior temporal gyrus; MMSE = Mini-Mental State Examination; MTL = medial temporal lobe; NvR = novel-vs-repeated; ROI = region of interest; TE = echo time; TR = repetition time.
PMID: 17893294 [PubMed - as supplied by publisher]
- Neuropsychology Abstract Of The Day: Alzheimer's Disease
Relationships Between Behavioral Syndromes and Cognitive Domains in Alzheimer Disease: The Impact of Mood and Psychosis American Journal of Geriatric Psychiatry. 2011 Nov 1; Koppel J, Goldberg TE, Gordon ML, Huey E, Davies P, Keehlisen L, Huet S, Christen...
- Neuropsychology Abstract Of The Day: Fmri Protocol For Intrinsic Alertness
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- Neuropsychology Abstract Of The Day: Neurodegeneration In Alzheimer Disease
de Jong LW, van der Hiele K, Veer IM, Houwing JJ, Westendorp RG, Bollen EL, de Bruin PW, Middelkoop HA, van Buchem MA, & van der Grond J. Strongly reduced volumes of putamen and thalamus in Alzheimer's disease: An MRI study. Brain. 2008 Nov 20. Department...
- Neuropsychology Abstract Of The Day: Mild Cognitive Impairment (mci)
Karas G, Sluimer J, Goekoop R, van der Flier W, Rombouts S, Vrenken H, Scheltens P, Fox N, & Barkhof F. Amnestic Mild Cognitive Impairment: Structural MR Imaging Findings Predictive of Conversion to Alzheimer Disease. American Journal of Neuroradiology....
- Neuropsychology Abstract Of The Day: Mild Cognitive Impairment (mci)
Fleisher AS, Sun S, Taylor C, Ward CP, Gamst AC, Petersen RC, Jack CR, Aisen PS, & Thal LJ. Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment. Neurology. 2008 Jan 15; 70(3): 191-199. OBJECTIVE: To compare volumetric...
Neuroscience
Neuropsychology Abstract of the Day: Alzheimer's Disease (AD), fMRI, and Cognition
Diamond EL, Miller S, Dickerson BC, Atri A, Depeau K, Fenstermacher E, Pihlajamäki M, Celone K, Salisbury S, Gregas M, Rentz D, & Sperling RA. Relationship of fMRI activation to clinical trial memory measures in Alzheimer disease. Neurology. 2007 Sep 25; 69(13): 1331-1341.
Memory Disorders Unit, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115
BACKGROUND: Functional MRI (fMRI) has shown promise as a tool to characterize altered brain function in Alzheimer disease (AD) and for use in proof of concept clinical trials. FMRI studies of subjects with AD have demonstrated altered hippocampal and neocortical activation while encoding novel stimuli compared to older controls. However, the relationship between fMRI activation and performance on standardized clinical trial memory measures has not been fully investigated. OBJECTIVE: To determine whether patterns of activation during an associative-memory fMRI paradigm correlate with performance on memory measures used in AD clinical trials. METHODS: Twenty-nine subjects with AD underwent neuropsychological testing, including the AD Assessment Scale (ADAS-Cog), and an associative-encoding fMRI paradigm. Scores were entered as regressors in SPM2 analyses of the differential fMRI activation to novel-vs-repeated (NvR) stimuli. To account for cerebral atrophy, native-space structure-function analyses were performed with subjects' high-resolution structural images. RESULTS: Performance on the ADAS-Cog verbal memory component, and the ADAS-Cog total score, correlated with NvR activation in left superior temporal (p = 0.0003; r = -0.51) and left prefrontal (p = 0.00001; r = -0.63) cortices. In a subgroup with more extensive neuropsychological testing (n = 14), performance on the Free and Cued Selective Reminding Test was correlated with activation in these same regions. fMRI activation remained correlated with performance even when accounting for atrophy. CONCLUSIONS: The relationship between functional MRI (fMRI) activation and standardized memory measures supports the potential use of fMRI to investigate regional mechanisms of treatment response in clinical trials of novel therapies for Alzheimer disease. GLOSSARY: AD = Alzheimer disease; ADAS-Cog = AD Assessment Scale; EPI = echoplanar imaging sequence; FA = flip angle; FCSRT = Free and Cued Selective Reminding Test; FLAME = FMRIB's Local Analysis of Mixed Effects; fMRI = Functional MRI; FOV = field of view; GLM = general linear model; HRF = hemodynamic response function; LFG = left fusiform gyrus; LPFC = left prefrontal cortex; LSTG = left superior temporal gyrus; MMSE = Mini-Mental State Examination; MTL = medial temporal lobe; NvR = novel-vs-repeated; ROI = region of interest; TE = echo time; TR = repetition time.
PMID: 17893294 [PubMed - as supplied by publisher]
- Neuropsychology Abstract Of The Day: Alzheimer's Disease
Relationships Between Behavioral Syndromes and Cognitive Domains in Alzheimer Disease: The Impact of Mood and Psychosis American Journal of Geriatric Psychiatry. 2011 Nov 1; Koppel J, Goldberg TE, Gordon ML, Huey E, Davies P, Keehlisen L, Huet S, Christen...
- Neuropsychology Abstract Of The Day: Fmri Protocol For Intrinsic Alertness
Revealing the Functional Neuroanatomy of Intrinsic Alertness Using fMRI: Methodological Peculiarities PLoS One. 2011; 6(9): e25453 Clemens B, Zvyagintsev M, Sack A, Heinecke A, Willmes K, Sturm W Abstract Clinical observations and neuroimaging data revealed...
- Neuropsychology Abstract Of The Day: Neurodegeneration In Alzheimer Disease
de Jong LW, van der Hiele K, Veer IM, Houwing JJ, Westendorp RG, Bollen EL, de Bruin PW, Middelkoop HA, van Buchem MA, & van der Grond J. Strongly reduced volumes of putamen and thalamus in Alzheimer's disease: An MRI study. Brain. 2008 Nov 20. Department...
- Neuropsychology Abstract Of The Day: Mild Cognitive Impairment (mci)
Karas G, Sluimer J, Goekoop R, van der Flier W, Rombouts S, Vrenken H, Scheltens P, Fox N, & Barkhof F. Amnestic Mild Cognitive Impairment: Structural MR Imaging Findings Predictive of Conversion to Alzheimer Disease. American Journal of Neuroradiology....
- Neuropsychology Abstract Of The Day: Mild Cognitive Impairment (mci)
Fleisher AS, Sun S, Taylor C, Ward CP, Gamst AC, Petersen RC, Jack CR, Aisen PS, & Thal LJ. Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment. Neurology. 2008 Jan 15; 70(3): 191-199. OBJECTIVE: To compare volumetric...