Alzheimer Disease: Borthakur A

Clark CM, Davatzikos C, Borthakur A, Newberg A, Leight S, Lee VM, Trojanowski JQ. · Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA. · Neurosignals. · Pubmed #18097155 No free full text.

Abstract: The increasing prevalence of Alzheimer's disease and the devastating consequences of late-life dementia motivates the drive to develop diagnostic biomarkers to reliably identify the pathology associated with this disorder. Strategies to accomplish this include the detection of altered levels of tau and amyloid in cerebrospinal fluid, the use of structural MRI to identify disease-specific patterns of regional atrophy and MRI T(1)rho to detect disease-related macromolecular protein aggregation, and the direct imaging of amyloid deposits using positron emission tomography and single photon emission computerized tomography. Success will facilitate the ability to reliably diagnose Alzheimer's disease while the symptoms of brain failure are mild and may provide objective measures of disease-modifying treatment efficacy.

Haris M, McArdle E, Fenty M, Singh A, Davatzikos C, Trojanowski JQ, Melhem ER, Clark CM, Borthakur A. · MMRRCC, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6100, USA. · J Magn Reson Imaging. · Pubmed #19388096 No free full text.

Abstract: PURPOSE: To evaluate the T1rho (T(1rho)) MRI relaxation time in hippocampus in the brain of Alzheimer's disease (AD), mild cognitive impairment (MCI), and control, and to determine whether the T(1rho) shows any significant difference between these cohorts. MATERIALS AND METHODS: With informed consent, AD (n = 49), MCI (n = 48), and age-matched control (n = 31) underwent T(1rho) MRI on a Siemens 1.5T Scanner. T(1rho) values were automatically calculated from the left and right hippocampus region using in-house developed software. Bonferroni post-hoc multiple comparisons was performed to compare the T(1rho) value among the different cohorts. RESULTS: Significantly higher T(1rho) values were observed both in AD (P = 0.000) and MCI (P = 0.037) cohorts compared to control; also, the T(1rho) in AD was significantly high over (P = 0.032) MCI. Hippocampus T(1rho) was 13% greater in the AD patients than control, while in MCI it was 7% greater than control. Hippocampus T(1rho) in AD patients was 6% greater than MCI. CONCLUSION: Higher hippocampus T(1rho) values in the AD patients might be associated with the increased plaques burden. A follow-up study would help to determine the efficacy of T(1rho) values as a predictor of developing AD in the control and MCI individuals.

Mellon EA, Pilkinton DT, Clark CM, Elliott MA, Witschey WR, Borthakur A, Reddy R. · Department of Radiology, MMRRCC, University of Pennsylvania, Philadelphia, PA, USA. · AJNR Am J Neuroradiol. · Pubmed #19213826 No free full text.

Abstract: BACKGROUND AND PURPOSE: There is significant interest in the development of novel noninvasive techniques for the diagnosis of Alzheimer disease (AD) and tracking its progression. Because MR imaging has detected alterations in sodium levels that correlate with cell death in stroke, we hypothesized that there would be alterations of sodium levels in the brains of patients with AD, related to AD cell death. MATERIALS AND METHODS: A total of 10 volunteers (5 with mild AD and 5 healthy control subjects) were scanned with a 20-minute sodium (23Na) MR imaging protocol on a 3T clinical scanner. RESULTS: After normalizing the signal intensity from the medial temporal lobes corresponding to the hippocampus with the ventricular signal intensity, we were able to detect a 7.5% signal intensity increase in the brains of patients with AD (AD group, 68.25% +/- 3.4% vs control group, 60.75% +/- 2.9%; P < .01). This signal intensity enhancement inversely correlated with hippocampal volume (AD group, 3.22 +/- 0.50 cm3 vs control group, 3.91 +/- 0.45 cm3; r2 = 0.50). CONCLUSIONS: This finding suggests that sodium imaging may be a clinically useful tool to detect the neuropathologic changes associated with AD.

Borthakur A, Sochor M, Davatzikos C, Trojanowski JQ, Clark CM. · MMRRCC, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104-6100, USA. · Neuroimage. · Pubmed #18479942 links to  free full text

Abstract: Alzheimer's disease (AD) is the most common form of dementia in the elderly. Classic symptoms of the disease include memory loss and confusion associated with the hallmark neuro-pathologic lesions of neurofibrillary tangles (NFT) and senile plaques (SP) and their sequelae, gray matter atrophy. Volumetric assessment methods measure tissue atrophy, which typically follows early biochemical changes. An alternate MRI contrast mechanism to visualize the early pathological changes is T1rho (or "T-1-rho"), the spin lattice relaxation time constant in the rotating frame, which determines the decay of the transverse magnetization in the presence of a "spin-lock" radio-frequency field. Macromolecular changes (in plaques and tangles) that accompany early AD are expected to alter bulk water T1rho relaxation times. In this work, we measure T1rho MRI on patients with clinically diagnosed AD, MCI and in age-matched cognitively normal control subjects in order to compare T1rho values with changes in brain volume in the same regions of the brain and demonstrate that T1rho can potentially constitute an important biomarker of AD.

Borthakur A, Gur T, Wheaton AJ, Corbo M, Trojanowski JQ, Lee VM, Reddy R. · Metabolic Magnetic Resonance Research & Computing Center (MMRRCC), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6100, USA. · J Magn Reson Imaging. · Pubmed #17036339 No free full text.

Abstract: PURPOSE: To demonstrate an MRI method for directly visualizing amyloid-beta (Abeta) plaques in the APP/PS1 transgenic (tg) mouse brain in vivo, and show that T1rho relaxation rate increases progressively with Alzheimer's disease (AD)-related pathology in the tg mouse brain. MATERIALS AND METHODS: We obtained in vivo MR images of a mouse model of AD (APP/PS1) that overexpresses human amyloid precursor protein, and measured T1rho via quantitative relaxometric maps. RESULTS: A significant decrease in T1rho was observed in the cortex and hippocampus of 12- and 18-month-old animals compared to their age-matched controls. There was also a correlation between changes in T1rho and the age of the animals. CONCLUSION: T1rho relaxometry may be a sensitive method for noninvasively determining AD-related pathology in APP/PS1 mice.