Tap Test Can Predict Cognitive Improvement in Patients With iNPH-Results From the Multicenter Prospective Studies SINPHONI-1 and -2

Madoka Nakajima, Shigeki Yamada, Masakazu Miyajima, Kaito Kawamura, Chihiro Akiba, Hiroaki Kazui, Etsuro Mori, Masatsune Ishikawa, SINPHONI-2 Investigators, Masaaki Hashimoto, Hideki Origasa, Haruko Yamamoto, Hajime Arai, Koreaki Mori, Shigenobu Nakamura, Tamotsu Miki, Kazunari Ishii, Hiroji Miyake, Nobumasa Kuwana, Naoyuki Samejima, Daisuke Kita, Takahiko Tokuda, Mitsuhito Mase, Satoru Mori, Yoshinaga Kajimoto, Teiji Nakayama, Osamu Hirai, Masatoshi Takeda, Chia-Cheng Chang, Isao Date, Masahiro Kameda, Takaharu Okada, Junichiro Hamada, Mitsuya Watanabe, Mitsunobu Kaijima, Souichi Sunada, Yoshihumi Hirata, Madoka Nakajima, Shigeki Yamada, Masakazu Miyajima, Kaito Kawamura, Chihiro Akiba, Hiroaki Kazui, Etsuro Mori, Masatsune Ishikawa, SINPHONI-2 Investigators, Masaaki Hashimoto, Hideki Origasa, Haruko Yamamoto, Hajime Arai, Koreaki Mori, Shigenobu Nakamura, Tamotsu Miki, Kazunari Ishii, Hiroji Miyake, Nobumasa Kuwana, Naoyuki Samejima, Daisuke Kita, Takahiko Tokuda, Mitsuhito Mase, Satoru Mori, Yoshinaga Kajimoto, Teiji Nakayama, Osamu Hirai, Masatoshi Takeda, Chia-Cheng Chang, Isao Date, Masahiro Kameda, Takaharu Okada, Junichiro Hamada, Mitsuya Watanabe, Mitsunobu Kaijima, Souichi Sunada, Yoshihumi Hirata

Abstract

Background: We analyzed the predictive value of the tap test (TT) on the outcome of cerebrospinal fluid (CSF) shunting in patients with idiopathic normal pressure hydrocephalus (iNPH) and cognitive impairment up to 12 months postoperatively. Methods: We analyzed the data of two prospective multicenter studies on ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS) use in iNPH patients. We selected patients with Mini-Mental State Examination (MMSE) scores ≤ 26 points as study subjects. We used a multivariate logistic regression model to obtain the optimal threshold of MMSE scores after TT to predict the score improvement at 12 months following shunting and that helped to control for confounding factors such as age and MMSE scores before TT. We used logistic regression models to identify variables with age-adjusted odds ratio (A-OR) and multivariate-adjusted OR (M-OR). Results: For an improvement of ≥3 points in the MMSE score cutoff 7 days following TT in VPS and LPS cohort studies, the MMSE scores improved by 6 points after 12 months. The VPS cohort had sensitivity, specificity, and area under the curve (AUC) of 69.2, 73.7, and 0.771%, respectively; however, for the LPS cohort, they were 86.2, 90.9, and 0.906%, respectively. For MMSE scores that improved by ≥3 points in patients after the TT, the possibility of an improvement by 6 points at 12 months following CSF shunt had A-OR 7.77 and M-OR 6.3 times for the VPS, and A-OR 62.3 and M-OR 59.6 times for the LPS cohort. Conclusion: CSF shunting contributes to improved cognitive function in iNPH patients. Furthermore, MMSE score evaluation at the TT can sensitively predict improvement in postoperative MMSE scores following LPS intervention. Clinical Trial Registration: SINPHONI-1 (ClinicalTrials.gov, no. NCT00221091), first posted: September 22, 2005. SINPHONI-2 [University Hospital Medical Information Network (UMIN) Clinical Trials no. UMIN000002730], the posted: February 1, 2010.

Keywords: Mini-Mental State Examination; cerebrospinal fluid shunt; cognitive function; healthy life expectancy; normal pressure hydrocephalus.

Conflict of interest statement

This investigator-initiated study was supported in part by Johnson & Johnson K.K. and Nihon Medi-Physics Co. Ltd. This work was also supported in part by the Ministry of Health, Labor, and Welfare of Japan (2014-Nanchi-General-052), and by Grants-in-Aid for Scientific Research (grant numbers 16KK0187, 17K10908, 18H02916, and 20K09398) from the Japan Society for the Promotion of Science. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. MN has received speakers' honoraria from Johnson & Johnson K.K., Janssen Pharmaceutical K.K., and Medtronic, Inc. SY received speaker honoraria from Johnson & Johnson, K.K. and Medtronic, Inc. MM has received speaker's honoraria from Johnson & Johnson K.K., Nihon Medi-Physics Co. Ltd., Medtronic, Inc., Eisai Inc., and Daiichi-Sankyo Co., Ltd. HK has received speakers' honoraria from Johnson & Johnson K.K., Nihon Medi Physics Co. Ltd., Medtronic, Inc., Ono Pharmaceutical Co., Ltd, Pfizer Inc., Eisai Inc., Daiichi-Sankyo Co., Ltd., Novartis Pharma K.K., Janssen Pharmaceutical K.K., and Takeda Pharmaceutical Co., Ltd. EM has received research grants from Eisai Co. Ltd. and Fuji Film RI, consulting fees from Lundbeck, and speaker's honoraria from Johnson & Johnson K.K., Nihon Medi-Physics Co. Ltd., Medtronic, Inc., Eisai, Co., Ltd., Daiichi Sankyo Co., Ltd., Janssen Pharmaceutical K.K., Novartis Pharma K.K., and Ono Pharmaceutical Co. Ltd. MI received speaker honoraria from Johnson & Johnson, K.K. and Medtronic, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Nakajima, Yamada, Miyajima, Kawamura, Akiba, Kazui, Mori, Ishikawa and the SINPHONI-2 Investigators.

Figures

Figure 1
Figure 1
Flow chart displaying patients with probable iNPH and MMSE scores ≤26 before TT. CSF, cerebrospinal fluid; LPS, lumboperitoneal shunt; MMSE, Mini-Mental State Examination; iNPH, idiopathic normal pressure hydrocephalus; TT, tap test; VPS, ventriculoperitoneal shunt.
Figure 2
Figure 2
Changes in average MMSE scores for subjects with an MMSE score ≤26 during research participation. The changes in MMSE score of the cohort are shown as median MMSE score (solid line), 25–75% (dashed line). In SINPHONI-1, the median MMSE score (25–75%) are 20 (15–24) before tap test (TT), 22 (17–26) after TT, 23 (20–27) at 3 months, 24 (21–27) at 6 months, and 25 (21–27) at 12 months after VPS, respectively. For the immediate group in SINPHONI-2, the median MMSE scores are 22 (16.5–24) before TT, 21 (17–24) after TT, 23 (18–26) at 3, 6 months, and 23 (19–26.75) at 12 months after LPS, respectively. For the postpone group in SINPHONI-2, the median MMSE scores are 19 (14–23) before TT, 21 (14–24) after TT, 20 (13–22) at 3 months later, 21 (15–25) at 3 months, 22 (13–25) at 6 months, and 21 (14–24) at 12 months after VPS, respectively. CSF, cerebrospinal fluid; LPS, lumboperitoneal shunt; MMSE, Mini-Mental State Examination; VPS, ventriculoperitoneal shunt; SINPHONI, a multicenter, prospective cohort study of iNPH on neurological improvements; TT, tap test.
Figure 3
Figure 3
MMSE score changes after the tap test. Distribution of dementia severity grades before and after the tap test, according to MMSE scores in SINPHONI-1 and SINPHONI-2. Numbers in each box indicate the number of patients. Blue, green, and red boxes indicate patients in “excellent improvement,” “improvement,” and “worse” groups. Spearman's rank correlation coefficient and p-value between before and after the tap test are ρ: 0.83 (p < 0.001) in SINPHONI-1 and ρ: 0.85 (p < 0.001) in SINPHONI-2, respectively. G, grade; SINPHONI, study of idiopathic normal pressure hydrocephalus on neurological improvement.
Figure 4
Figure 4
MMSE score changes between before and 12 months after shunting. (A) The distribution of preoperative and postoperative grades of dementia severity, according to the MMSE scores. Numbers in each box indicate the number of patients. Spearman's rank correlation coefficient (ρ) and p-value between before and 12 months after shunting are ρ: 0.51 (p < 0.001) in VPS and ρ: 0.66 (p < 0.001) in LPS cohort, respectively. (B) Changes after shunt treatment in severity classification by MMSE scores. CSF, cerebrospinal fluid; MMSE, Mini-Mental State Examination; LPS, lumboperitoneal shunt; and VPS, ventriculoperitoneal shunt.
Figure 5
Figure 5
Tap test as predictor of postoperative MMSE scores. The optimal threshold, sensitivity, and specificity of the MMSE score during the tap test to predict MMSE improvement at 12 months after shunting have been analyzed using receiver operating characteristic analysis. The light blue line shows the approximate line. AUC, area under the receiver operating characteristic curve; MMSE, Mini-Mental State Examination; LP, lumboperitoneal; and VP, ventriculoperitoneal.

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