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Prediction of outcomes in MCI with 123I-IMP-CBF SPECT: a multicenter prospective cohort study
Authors:Kengo Ito  Etsuro Mori  Hidenao Fukuyama  Kazunari Ishii  Yukihiko Washimi  Takashi Asada  Satoru Mori  Kenichi Meguro  Shin Kitamura  Haruo Hanyu  Seigo Nakano  Hiroshi Matsuda  Yasuo Kuwabara  Kazuo Hashikawa  Toshimitsu Momose  Yoshitaka Uchida  Jun Hatazawa  Satoshi Minoshima  Kenji Kosaka  Tatsuo Yamada  Yoshiharu Yonekura
Affiliation:1. Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 35 Gengo Morioka-cho, Obu-shi, Aichi, 474-8511, Japan
2. Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University, Sendai, Japan
3. Human Brain Research Center, Kyoto University, Kyoto, Japan
4. Department of Radiology, Kinki University, Osakasayama, Japan
5. Department of Outpatient Services, National Center for Geriatrics and Gerontology, Obu, Japan
6. Department of Neuropsychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan
7. School of Human Nursing, The University of Shiga Prefecture, Hikone, Japan
8. Department of Geriatric Behavioral Neurology, Tohoku University, Sendai, Japan
9. Department of Neurology, Nippon Medical School Musashi Kosugi Hospital, Kawasaki, Japan
10. Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan
11. Sumida Hospital, Tokyo, Japan
12. Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Kodaira, Japan
13. Department of Radiology, Fukuoka University Hospital, Fukuoka, Japan
14. Department of Cerebrovascular Disease, Osaka Minami Medical Center, Kawachinagano, Japan
15. Department of Radiology, Tokyo University, Tokyo, Japan
16. Department of Radiology, Chiba University, Chiba, Japan
17. Department of Nuclear Medicine, Osaka University, Suita, Japan
18. Department of Radiology, University of Washington, Seattle, WA, USA
19. Yokohama Houyuu Hospital, Yokohama, Japan
20. Department of Neurology, Fukuoka University, Fukuoka, Japan
21. National Institute of Radiological Sciences, Chiba, Japan
Abstract:

Objective

The multicenter prospective cohort study (Japan Cooperative SPECT Study on Assessment of Mild Impairment of Cognitive Function: J-COSMIC) aimed to examine the value of 123I-N-isopropyl-4-iodoamphetamine cerebral blood flow (IMP-CBF) SPECT in regards to early diagnosis of Alzheimer’s disease (AD) in patients with mild cognitive impairment (MCI).

Methods

Three hundred and nineteen patients with amnestic MCI at 41 participating institutions each underwent clinical and neuropsychological examinations and 123I-IMP-CBF SPECT at baseline. Subjects were followed up periodically for 3 years, and progression to dementia was evaluated. SPECT images were classified as AD/DLB (dementia with Lewy bodies) pattern and non-AD/DLB pattern by central image interpretation and automated region of interest (ROI) analysis, respectively. Logistic regression analyses were used to assess whether baseline 123I-IMP-CBF SPECT was predictive of longitudinal clinical outcome.

Results

Ninety-nine of 216 amnestic MCI patients (excluding 3 cases with epilepsy (n = 2) or hydrocephalus (n = 1) and 100 cases with incomplete follow-up) converted to AD within the observation period. Central image interpretation and automated ROI analysis predicted conversion to AD with 56 and 58 % overall diagnostic accuracy (sensitivity, 76 and 81 %; specificity, 39 and 37 %), respectively. Multivariate logistic regression analysis identified SPECT as a predictor, which distinguished AD converters from non-converters. The odds ratio for a positive SPECT to predict conversion to AD with automated ROI analysis was 2.5 and combining SPECT data with gender and mini-mental state examination (MMSE) further improved classification (joint odds ratio 20.08).

Conclusions

123I-IMP-CBF SPECT with both automated ROI analysis and central image interpretation was sensitive but relatively nonspecific for prediction of clinical outcome during the 3-year follow-up in individual amnestic MCI patients. A combination of statistically significant predictors, both SPECT with automated ROI analysis and neuropsychological evaluation, may increase predictive utility.
Keywords:
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