J Neurol Res

Journal of Neurology Research, ISSN 1923-2845 print, 1923-2853 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Neurol Res and Elmer Press Inc

Journal website https://jnr.elmerpub.com

Original Article

Volume 15, Number 3, August 2025, pages 105-116

Neuroprotective Effects of Calcium Channel Blockers on Parkinson’s Disease Development: A Population Cohort Study

Figure 1. Cohort definition flowchart for cohort 1 (CCB) and cohort 2 (BB). ACE: angiotensin-converting enzyme; BB: beta-blocker; CCB: calcium channel blocker.

Figure 2. Propensity score density function graphs showing cohort 1 (CCB) and cohort 2 (BB). BB: beta-blocker; CCB: calcium channel blocker.

Figure 3. Kaplan-Meier survival graph comparing cohort 1 (CCB) vs. cohort 2 (BB). BB: beta-blocker; CCB: calcium channel blocker.

Figure 5. Propensity score density function graphs showing cohort 3 (dihydropyridine) and cohort 4 (non-dihydropyridine).

Figure 6. Kaplan-Meier survival graph comparing cohort 3 (dihydropyridine) vs. cohort 4 (non-dihydropyridine).

Figure 7. Cohort definition with the participant numbers and inclusion and exclusion criteria for cohort 5 (amlodipine) vs. cohort 6 (nifedipine).

Figure 8. Propensity score density function graphs showing cohort 5 (amlodipine) and cohort 6 (nifedipine).

**Table 1.** Demographics of the Participants of Cohort 1 (CCB) and Cohort 2 (BB) Before and After Propensity Score Matching
Demographics	Mean ± SD	Patients	% of cohort	P-value	Std diff.
BB: beta-blocker; CCB: calcium channel blocker; SD: standard deviation.
Cohort 1 (N = 385,522) and cohort 2 (N = 750,562) before propensity score matching
Age at index				< 0.001	0.099
Cohort 1	59.6 ± 16.7	368,234	100%
Cohort 2	61.2 ± 15.7	718,165	100%
Female				< 0.001	0.037
Cohort 1		189,836	51.6%
Cohort 2		356,797	49.7%
Male				0.001	0.007
Cohort 1		169,271	46.0%
Cohort 2		332,589	46.3%
Cohort 1 (N = 364,898) and cohort 2 (N = 364,898) after propensity score matching
Age at index				0.354	0.002
Cohort 1	60.1 ± 16.0	364,898	100%
Cohort 2	60.1 ± 15.9	364,898	100%
Female				0.001	0.008
Cohort 1		187,707	51.4%
Cohort 2		189,173	51.8%
Male				0.001	0.008
Cohort 1		168,064	46.1%
Cohort 2		166,602	45.7%

Table 1. Demographics of the Participants of Cohort 1 (CCB) and Cohort 2 (BB) Before and After Propensity Score Matching

Demographics

Mean ± SD

Patients

% of cohort

P-value

Std diff.

BB: beta-blocker; CCB: calcium channel blocker; SD: standard deviation.

Cohort 1 (N = 385,522) and cohort 2 (N = 750,562) before propensity score matching

Age at index

< 0.001

0.099

Cohort 1

59.6 ± 16.7

368,234

100%

Cohort 2

61.2 ± 15.7

718,165

100%

Female

< 0.001

0.037

Cohort 1

189,836

51.6%

Cohort 2

356,797

49.7%

Male

0.001

0.007

Cohort 1

169,271

46.0%

Cohort 2

332,589

46.3%

Cohort 1 (N = 364,898) and cohort 2 (N = 364,898) after propensity score matching

Age at index

0.354

0.002

Cohort 1

60.1 ± 16.0

364,898

100%

Cohort 2

60.1 ± 15.9

364,898

100%

Female

0.001

0.008

Cohort 1

187,707

51.4%

Cohort 2

189,173

51.8%

Male

0.001

0.008

Cohort 1

168,064

46.1%

Cohort 2

166,602

45.7%

**Table 2.** Racial Demographics of Participants in Cohort 1 (CCB)
Race	Patients	% of the cohort
White	195,442	53.69%
Black/African American	71,559	19.66%
Asian	27,086	7.44%
Native Hawaiian/other Pacific Islander	1,488	0.41%
American Indian/Alaska Native	784	0.22%
Other	13,023	3.63%
Unknown race	54,422	14.95%

Table 2. Racial Demographics of Participants in Cohort 1 (CCB)

Race

Patients

% of the cohort

White

195,442

53.69%

Black/African American

71,559

19.66%

Asian

27,086

7.44%

Native Hawaiian/other Pacific Islander

1,488

0.41%

American Indian/Alaska Native

784

0.22%

Other

13,023

3.63%

Unknown race

54,422

14.95%

**Table 3.** Racial Demographics of Participants in Cohort 2 (BB)
Race	Patients	% of the cohort
White	500,955	69.81%
Black/African American	61,270	13.5%
Asian	31,371	4.37%
Native Hawaiian/other Pacific Islander	4,467	0.62%
American Indian/Alaska Native	1,592	0.22%
Other	13,023	3.63%
Unknown race	96,847	13.5%

Table 3. Racial Demographics of Participants in Cohort 2 (BB)

Race

Patients

% of the cohort

White

500,955

69.81%

Black/African American

61,270

13.5%

Asian

31,371

4.37%

Native Hawaiian/other Pacific Islander

4,467

0.62%

American Indian/Alaska Native

1,592

0.22%

Other

13,023

3.63%

Unknown race

96,847

13.5%

**Table 4.** Outcome Diagnosis as Parkinson Disease as Well as the Settings Under Which the Different Analyses Are Run
Outcome definition
Diagnosis (UMLS: ICD-10-CM: G20)	Parkinson’s disease
Settings for the performed analyses
Risk analysis	Excluding patients with outcome prior to the time window
Kaplan-Meier survival analysis	Excluding patients with outcome prior to the time window
Number of instances analysis	Excluding patients with outcome prior to the time window. Excluding patients with zero outcomes. Counts are grouped by visit

Table 4. Outcome Diagnosis as Parkinson Disease as Well as the Settings Under Which the Different Analyses Are Run

Outcome definition

Diagnosis (UMLS: ICD-10-CM: G20)

Parkinson’s disease

Settings for the performed analyses

Risk analysis

Excluding patients with outcome prior to the time window

Kaplan-Meier survival analysis

Excluding patients with outcome prior to the time window

Number of instances analysis

Excluding patients with outcome prior to the time window. Excluding patients with zero outcomes. Counts are grouped by visit

**Table 5.** Risk Analysis Comparing CCB (Cohort 1) vs. BB (Cohort 2 Which Is the Control)
Cohort	Patients in cohort	Patients with outcome	Risk
Risk analysis excluding patients with outcome prior to the time window. BB: beta-blocker; CCB: calcium channel blocker; CI: confidence interval.
1	362,933	1,043	0.003
2	362,425	1,420	0.004
Risk analysis		95% CI
Risk difference	-0.001	(-0.001 to -0.001)
Risk ratio	0.733	(0.677 - 0.794)
Odds ratio	0.733	(0.676 - 0.794)
Hazard ratio	0.776	(0.716 - 0.840)

Table 5. Risk Analysis Comparing CCB (Cohort 1) vs. BB (Cohort 2 Which Is the Control)

Cohort

Patients in cohort

Patients with outcome

Risk

Risk analysis excluding patients with outcome prior to the time window. BB: beta-blocker; CCB: calcium channel blocker; CI: confidence interval.

362,933

1,043

0.003

362,425

1,420

0.004

Risk analysis

95% CI

Risk difference

-0.001

(-0.001 to -0.001)

Risk ratio

0.733

(0.677 - 0.794)

Odds ratio

0.733

(0.676 - 0.794)

Hazard ratio

0.776

(0.716 - 0.840)

**Table 6.** Kaplan-Meier Survival Analysis Comparing Cohort 1 (CCB) vs. Cohort 2 (BB)
Cohort	Patients in cohort	Patients with outcome	Median survival (days)	Survival probability at end of time window
Kaplan-Meier survival analysis excluding patients with outcome prior to the time window. BB: beta-blocker; CCB: calcium channel blocker; CI: confidence interval.
1	362,933	1,043	-	96.86%
2	362,425	1,420	-	98.27%

Table 6. Kaplan-Meier Survival Analysis Comparing Cohort 1 (CCB) vs. Cohort 2 (BB)

Cohort

Patients in cohort

Patients with outcome

Median survival (days)

Survival probability at end of time window

Kaplan-Meier survival analysis excluding patients with outcome prior to the time window. BB: beta-blocker; CCB: calcium channel blocker; CI: confidence interval.

362,933

1,043

96.86%

362,425

1,420

98.27%

**Table 7.** Demographics of the Participants of Cohort 3 (Dihydropyridine) and Cohort 4 (Non-Dihydropyridine) Before and After Propensity Score Matching
Demographics	Mean ± SD	Patients	% of cohort	P-value	Std diff.
SD: standard deviation.
Cohort 3 (N = 323,884) and cohort 4 (N = 63,745) before propensity score matching
Age at index				< 0.001	0.241
Cohort 3	59.1 ± 16.4	310,581	100%
Cohort 4	63.0 ± 16.5	60,212	100%
Female				< 0.001	0.091
Cohort 3		157,695	50.8%
Cohort 4		33,296	55.3%
Male				< 0.001	0.103
Cohort 3		145,692	46.9%
Cohort 4		25,182	41.8%
Cohort 3 (N = 60,212) and cohort 4 (N = 60,212) after propensity score matching
Age at Index				0.994	< 0.001
Cohort 3	63.0 ± 16.5	60,212	100%
Cohort 4	63.0 ± 16.5	60,212	100%
Female				1	< 0.001
Cohort 3		33,296	55.3%
Cohort 4		33,296	55.3%
Male				0.991	< 0.001
Cohort 3		25,184	41.8%
Cohort 4		25,182	41.8%

Table 7. Demographics of the Participants of Cohort 3 (Dihydropyridine) and Cohort 4 (Non-Dihydropyridine) Before and After Propensity Score Matching

Demographics

Mean ± SD

Patients

% of cohort

P-value

Std diff.

SD: standard deviation.

Cohort 3 (N = 323,884) and cohort 4 (N = 63,745) before propensity score matching

Age at index

< 0.001

0.241

Cohort 3

59.1 ± 16.4

310,581

100%

Cohort 4

63.0 ± 16.5

60,212

100%

Female

< 0.001

0.091

Cohort 3

157,695

50.8%

Cohort 4

33,296

55.3%

Male

< 0.001

0.103

Cohort 3

145,692

46.9%

Cohort 4

25,182

41.8%

Cohort 3 (N = 60,212) and cohort 4 (N = 60,212) after propensity score matching

Age at Index

0.994

< 0.001

Cohort 3

63.0 ± 16.5

60,212

100%

Cohort 4

63.0 ± 16.5

60,212

100%

Female

< 0.001

Cohort 3

33,296

55.3%

Cohort 4

33,296

55.3%

Male

0.991

< 0.001

Cohort 3

25,184

41.8%

Cohort 4

25,182

41.8%

**Table 8.** Risk Analysis Numbers of Analysis Set 2 Which Included People Treated With Cohort 3 (Dihydropyridine) and Cohort 4 (Non-Dihydropyridine)
Cohort	Patients in cohort	Patients with outcome	Risk
Risk analysis excluding patients with outcome prior to the time window. CI: confidence interval.
3	59,835	203	0.003
4	59,808	199	0.003
Risk analysis		95% CI
Risk difference	0.00006	(-0.001 to 0.001)
Risk ratio	1.020	(0.839 - 1.239)
Odds ratio	1.020	(0.838 - 1.240)
Hazard ratio	0.982	(0.808 - 1.194)

Table 8. Risk Analysis Numbers of Analysis Set 2 Which Included People Treated With Cohort 3 (Dihydropyridine) and Cohort 4 (Non-Dihydropyridine)

Cohort

Patients in cohort

Patients with outcome

Risk

Risk analysis excluding patients with outcome prior to the time window. CI: confidence interval.

59,835

203

0.003

59,808

199

0.003

Risk analysis

95% CI

Risk difference

0.00006

(-0.001 to 0.001)

Risk ratio

1.020

(0.839 - 1.239)

Odds ratio

1.020

(0.838 - 1.240)

Hazard ratio

0.982

(0.808 - 1.194)

**Table 9.** Kaplan-Meier Survival Analysis Comparing Cohort 3 (Dihydropyridine) vs. Cohort 4 (Non-Dihydropyridine)
Cohort	Patients in cohort	Patients with outcome	Median survival (days)	Survival probability at end of time window
Kaplan-Meier survival analysis excluding patients with outcome prior to the time window.
3	59,835	203	-	98.30%
4	59,808	199	-	98.69%

Table 9. Kaplan-Meier Survival Analysis Comparing Cohort 3 (Dihydropyridine) vs. Cohort 4 (Non-Dihydropyridine)

Cohort

Patients in cohort

Patients with outcome

Median survival (days)

Survival probability at end of time window

Kaplan-Meier survival analysis excluding patients with outcome prior to the time window.

59,835

203

98.30%

59,808

199

98.69%

**Table 10.** Demographics of the Participants of Cohort 5 (Amlodipine) and Cohort 6 (Nifedipine) Before and After Propensity Score Matching
Demographics	Mean ± SD	Patients	% of cohort	P-value	Std diff.
Cohort 5 (N = 288,980) and cohort 6 (N = 19,882) before propensity score matching
Age at index				< 0.001	0.338
Cohort 5	59.6 ± 15.8	277,109	100%
Cohort 6	53.7 ± 19.1	18,918	100%
Female				< 0.001	0.310
Cohort 5		137,633	49.7%
Cohort 6		12,259	64.8%
Male				< 0.001	0.295
Cohort 5		132,714	47.9%
Cohort 6		6,347	33.6%
Cohort 5 (N = 18,918) and cohort 6 (N = 18,918) after propensity score matching
Age at index				0.999	< 0.001
Cohort 5	53.7 ± 19.1	18,918	100%
Cohort 6	53.7 ± 19.1	18,918	100%
Female				1	< 0.001
Cohort 5		12,259	64.8%
Cohort 6		12,259	64.8%
Male				0.991	< 0.001
Cohort 5		6,348	33.6%
Cohort 6		6,347	33.6%

Table 10. Demographics of the Participants of Cohort 5 (Amlodipine) and Cohort 6 (Nifedipine) Before and After Propensity Score Matching

Demographics

Mean ± SD

Patients

% of cohort

P-value

Std diff.

Cohort 5 (N = 288,980) and cohort 6 (N = 19,882) before propensity score matching

Age at index

< 0.001

0.338

Cohort 5

59.6 ± 15.8

277,109

100%

Cohort 6

53.7 ± 19.1

18,918

100%

Female

< 0.001

0.310

Cohort 5

137,633

49.7%

Cohort 6

12,259

64.8%

Male

< 0.001

0.295

Cohort 5

132,714

47.9%

Cohort 6

6,347

33.6%

Cohort 5 (N = 18,918) and cohort 6 (N = 18,918) after propensity score matching

Age at index

0.999

< 0.001

Cohort 5

53.7 ± 19.1

18,918

100%

Cohort 6

53.7 ± 19.1

18,918

100%

Female

< 0.001

Cohort 5

12,259

64.8%

Cohort 6

12,259

64.8%

Male

0.991

< 0.001

Cohort 5

6,348

33.6%

Cohort 6

6,347

33.6%

**Table 11.** Risk Analysis Numbers of Analysis Set 2 Which Included People Treated With Cohort 5 (Amlodipine) vs. Cohort 6 (Nifedipine)
Cohort	Patients in cohort	Patients with outcome	Risk
Risk analysis excluding patients with outcome prior to the time window. CI: confidence interval.
5	18,831	36	0.002
6	18,826	31	0.002
Risk analysis		95% CI
Risk difference	0.0003	(-0.001 to 0.001)
Risk ratio	1.161	(0.719 - 1.876)
Odds ratio	1.161	(0.718 - 1.878)
Hazard ratio	1.109	(0.686 - 1.793)

Table 11. Risk Analysis Numbers of Analysis Set 2 Which Included People Treated With Cohort 5 (Amlodipine) vs. Cohort 6 (Nifedipine)

Cohort

Patients in cohort

Patients with outcome

Risk

Risk analysis excluding patients with outcome prior to the time window. CI: confidence interval.

18,831

0.002

18,826

0.002

Risk analysis

95% CI

Risk difference

0.0003

(-0.001 to 0.001)

Risk ratio

1.161

(0.719 - 1.876)

Odds ratio

1.161

(0.718 - 1.878)

Hazard ratio

1.109

(0.686 - 1.793)

**Table 12.** Kaplan-Meier Survival Analysis Comparing Cohort 5 (Amlodipine) vs. Cohort 6 (Nifedipine)
Cohort	Patients in cohort	Patients with outcome	Median survival (days)	Survival probability at end of time window
Kaplan-Meier survival analysis excluding patients with outcome prior to the time window.
5	18,831	36	-	99.71%
6	18,826	31	-	99.74%

Table 12. Kaplan-Meier Survival Analysis Comparing Cohort 5 (Amlodipine) vs. Cohort 6 (Nifedipine)

Cohort

Patients in cohort

Patients with outcome

Median survival (days)

Survival probability at end of time window

Kaplan-Meier survival analysis excluding patients with outcome prior to the time window.

18,831

99.71%

18,826

99.74%