Efficacy of Magnetic Resonance Spectroscopy (MRS) for Clinical Diagnosis of Alzheimer´s Disease Cat-Huong NGUY1, Mya ZAPATA2, Frederick SHIC2, Alexander LIN2, David Shieh3, Norman CHIEN3, Brian ROSS2

1Rudi Schulte Research Institute, Santa Barbara, California United States; 2Huntington Medical Research Institutes, Pasadena, California United States; 3Huntington Memorial Hospital, Pasadena, California United States; Introduction Alzheimer´s Disease (AD) leads to cognitive decline in the elderly. The currently accepted standard for the diagnosis of AD is clinical by DSM IV standard which has been determined to be 80% accurate compared to the "gold standard" which is autopsy [1]. The MRS diagnosis of AD uses two metabolites observable in 1H MRS: N-acetyl aspartate (NAA) and myo-inositol (mI). Alzheimer patients have been shown to have increased levels of mI, which is associated with the pathogenesis of AD, as seen in its correlation with Down´s Syndrome [2]. Despite accurate diagnosis using MRS [3], it has not yet been accepted as part of clinical diagnosis. Correlation of MRS with postmortem diagnosis has not to our knowledge been previously attempted. This study will assess the efficacy of MRS in distinguishing AD from other causes of dementia and normal aging, relative to clinical diagnosis, and explore the feasibility of post-mortem validation. Subjects and Methods 1) A retrospective single blinded chart review was performed on 88 elderly patients (age: 79.3 ± 6.6) complaining of memory deficits and exhibiting early signs of dementia. Patients underwent a complete clinical evaluation, which involved tests under DSM IV standards such as vitamin B-12 deficiency, hydrocephalus, MMSE, etc. Short echo, single voxel, STEAM MRS (TE=30ms; TR=1.5s) was acquired in the occipital gray matter in all patients. AD diagnosis was determined by mI/Cr and NAA/Cr ratios as shown in Figure 1. MRS results were then factored into the clinical decision and a final diagnosis was determined. Kappa values were calculated comparing MRS diagnosis to initial and final clinical evaluations. Efficacy was then determined by binary analysis and changes between initial and final diagnosis due to MRS. 2) A retrospective single blind review of 476 patients MRS findings were evaluated against (A) mortality data (B) autopsy diagnosis. Results Clinical diagnosis before MRS: of the 88 patients, 21 were clinically diagnosed with AD, and 67 were classified as non-AD. MRS exam: 39 patients were diagnosed with AD, and 49 patients were non-AD. This yields a kappa (K) value of 0.04 which indicates poor agreement between MRS and initial clinical diagnosis. Final clinical diagnosis after MRS: When a second (blinded) clinician was offered MRS results, diagnosis was re-evaluated. 38 patients were diagnosed with AD and 50 were non-AD. Thus yielding K=0.61, which demonstrate a good agreement between MRS and final clinical diagnosis. The kappa value between original and final diagnosis is 0.25 The impact of MRS on clinical management of these AD patients can be demonstrated by examining the changes made between initial and final diagnosis and their agreements with MRS results. In 67 patients who were initially diagnosed as non-AD, MRS results were positive for AD and the final diagnosis was changed to agree with MRS in 20 patients. In 21 patients originally diagnosed with AD, MRS did not agree and subsequently the final diagnosis reflected a negative diagnosis in 5 patients. These patients were immediately taken of AD medications and treated for depression or other pathologies. This reflects that 29% of the patients would have been incorrectly diagnosed had it not been for MRS. MRS confirmed initial diagnosis in 53% of the patients, thus reaffirming treatment decisions. In the remainder of the cases, MRS did not affect decision-making. 115/476 patients subject to MRS for clinical MRS for dementia between 1990-2000 have died at the time of this analysis. Autopsy has been traced in only 5/115 subjects. A prospective study over ten years will be essential to resolve this question. Conclusions (1) MRS demonstrates efficacy in differentiating AD from other dementing illnesses. Addition of 1H MRS to DSM IV standards could significantly increase detection of AD early in its course when clinical diagnosis is uncertain, which may lead to prompt intervention.

(2) The clinical application of the "gold standard" to MRS requires more open access to currently unnecessarily secretive ("confidential") autopsy records.

Figure 1: 1H MRS in Occipital Cortex to Discriminate Patients with AD.

Figure 2: Proton magnetic resonance spectra of a patient with probable Alzheimer disease compared to an age-related normal. Peaks are a measure of concentration of individual metabolites. Creatine (the central peak) is the reference. Myo-inositol (mI); creatine (Cr); glutamine plus glutamate (Glx); N-acetylaspartate (NAA). References 1. Thal L et al. Neurology 1991;41:323. 2. Shonk T and Ross BD. Magn. Reson. Med. 1995;33:858-861. 3. Shonk et al. Radiology 1995;195:65-72.

Proc. Intl. Soc. Mag. Reson. Med 9 (2001)

989

Proc. Intl. Soc. Mag. Reson. Med 9 (2001)

989