Cognitive functions and health-related quality of life in men with benign prostatic hyperplasia and symptoms of overactive bladder when treated with a combination of tamsulosin and solifenacin in a higher dosage

Abstract

Aim: To study the cognitive functions and health-related quality of life (HRQoL) in individuals taking a combination of tamsulosin and solifenacin in a higher dosage.

Methods: All patients (n = 262) were assigned to group A (N = 93, tamsulosin 0.4 mg + solifenacin 10 mg per day), group B (N = 83, tamsulosin 0.4 mg + solifenacin 20 mg), and control group C (N = 86; tamsulosin 0.4 mg + placebo). The lower urinary tract (LUT) condition was assessed on the scales International Prostate Symptom Score, Over Active Bladder Awareness Tool and uroflowmetry. The state of cognitive status was assessed on the scales Mini-mental State Examination, Controlled Oral Word Association Test, Wechsler Adult Intelligence Scale-Revised, Wechsler III, Color Trails Test, California Verbal Learning Test.

Results: The values of cognitive function indicators in the individuals from all groups after treatment did not significantly differ from the respective values at the baseline (p > .05). The values of most HRQoL parameters of the functional state of the LUT significantly improved in groups A and B. A significant correlation between the state of cognitive status and HRQoL, as well as LUT was absent (r <0.3).

Conclusion: The combination of solifenacin in a double dosage along with tamsulosin can be recommended for elderly benign prostatic hyperplasia patients with overactive bladder symptoms.

Keywords:

• Overactive bladder; benign prostatic hyperplasia; cognitive functions; health-related quality of life; tamsulosin; solifenacin 

Introduction

As a rule, “benign prostatic hyperplasia” (BPH) occurs with infection, cholesterolemia and hormonal disorders (hypogonadism and/or hyperestrogenism). As a result of a combination of these factors, there is an unregulated proliferation of connective tissue, smooth muscle and glandular epithelium in the prostate gland [1]. The prevalence of BPH is 10.3% on average [2] and increases with age. While it can be 1–2% at the age of 40–49, it is 36% or more in persons older than 70 years [3]. The growth rate of the prostate in older men is from 2.0% to 2.5% per year on average [4,5]. The pathogenic mechanisms of BPH are highly researched; nevertheless, many new studies have come out lately specifying particular aspects of the pathogenesis of this disease [6–8]. Particularly, patients suffering from BPH are involved in studies aimed at researching association between triglyceride high-density lipoprotein cholesterol ratio [9], the influence of metabolic status on the disease development [10], impacts of a decrease in testosterone level [11,12]. Recently, several new interesting studies have appeared which consider the influence of a set of factors accompanying the aging process (associated diseases, lifestyle changes and others) on the BPH development with nocturia and other symptoms of overactive bladder (OAB) [13,14].

The authors of many studies note that the symptoms of BPH are combined with the symptoms of OAB in most patients [15,16]. However, these symptoms are often not verified, and the OAB remains unrecognized [17]. Today, apart from conventional treatment with the use of alpha-blocker [18] there is an active search for new treatment methods of BPH with OAB symptoms being carried out. Many researchers continue studying the efficiency of the UroLift prostate implant [19], testosterone-based medications [20], the thermobalancing therapy [21], as well as safety and efficiency of some other medications [22,23].

Meanwhile, in the treatment of BPH accompanied by OAB symptoms, very encouraging results have been obtained. It was found that the combination of alpha-blocker and antimuscarinic (AM) allows not only to slow the growth of prostate tissue, but also to reverse the development of OAB symptoms. In particular, this effect was observed with the simultaneous administration of tamsulosin and solifenacin [24].

Previously, we also examined the efficacy and safety of this combination of drugs using cystometry as a control instrument [25–28]. In particular, it was shown that at least 44% of patients with BPH have severe OAB symptoms, and the combined use of tamsulosin and solifenacin is accompanied by a statistically significant decrease in the number of episodes of urinary incontinence, daytime and night urination, as well as optimization of urodynamic parameters.

It is known that some AMs of the first generations, namely tolterodine and oxybutynin, can cause cognitive dysfunction in some patients. At the same time, there is abundant testimony that solifenacin and tamsulosin in standard dosages do not affect the cognitive abilities of patients. Nevertheless, some researchers point to the need for cautious use of AMs and alpha-blockers in elderly patients, given that “Even modest cognitive impairment in the elderly may negatively affect independence” [29]. In the available literature, we were not able to detect the results of an active study of cognitive function in persons with BPH and OAB symptoms taking solifenacin in a higher dosage simultaneously with tamsulosin. In papers describing the efficacy and safety of this combination, only data on patients’ complaints on certain side effects (dry mouth, nausea, etc.) are given. Also, there is no data about the effect of taking these drugs on health-related quality of life (HRQoL) in the literature. A few sources describe a positive effect on the quality of life in patients taking solifenacin and tamsulosin in standard therapeutic dosages.

Thus, the goal of our work was to study the cognitive functions and quality of life associated with health in individuals taking a combination of tamsulosin and solifenacin in a higher dosage.

Methods

Participants

A cohort study involved 262 men who were selected using the principles of randomization. The groups included individuals with newly diagnosed BPH (8–19 points for the International Prostate Symptom Score (I-PSS), residual urine volume ≤100 ml) [24], and OAB symptoms who had not previously taken tamsulosin and AM drugs. All persons included in the groups had at least 24 points on the Mini-mental State Examination (MMSE) scale, could understand the questions and gave written informed consent to participate in the experiment. The criteria for exclusion were: the presence of depression, affective disorder, schizophrenia, cerebral circulation disorder, epilepsy, Parkinson’s disease, Alzheimer’s disease, alcoholism, as well as any chronic somatic disease in the acute stage. Clinical characteristics of patients are presented in Table 1. In the preliminary analysis, it was found that the differences between the parameters of patients from the main and control groups were not statistically reliable.

Table 1. Clinical characteristic of patients with BPH and OAB (n = 262).

Parameters	Group A (n = 93)	Group B (n= 83)	Group C (n= 86)
Average age, years	62.8 (9.7)	66.8 (8.2)	66.0 (13.6)
IPSS questionnaire (in scores)
Incomplete emptying	2.5 (0.5)	2.4 (0.6)	1.9 (0.8)
Intermittency	2.1 (0.8)	2.6 (1.2)	2.2 (1.5)
Weak stream	2.5 (0.9)	2.0 (0.9)	1.9 (0.8)
Straining	3.3 (1.1)	1.1 (0.9)	1.7 (1.3)
Nocturia	2.4 (0.7)	2.5 (1.5)	2.6 (1.8)
Total	12.8 (5.3)	10.6 (3.8)	13.0 (2.3)
OAB-AT questionnaire (in scores)
Daytime frequency	5.1 (2.5)	4.9 (2.1)	4.9 (3.4)
Nighttime frequency	2.1 (1.4)	2.4 (1.4)	2.5 (1.6)
Urgency	3.2 (2.2)	2.8 (1.8)	2.7 (1.0)
Urgency incontinence	2.3 (0.8)	2.1 (0.9)	2.3 (0.8)
Urodynamic parameters (uroflowmetry)
PVR, ml	52.1 (12.7)	61.0 (11.9)	66.0 (17.8)
Qaver, ml/s	12.1 (3.4)	15.4 (7.3)	14.5 (8.0)
Qmax, ml/s	16.5 (5.9)	18.0 (6.5)	19.6 (7.7)

Remark: Group A (tamsulosin 0.4 mg + solifenacin 5 mg per day).

Group B (tamsulosin 0.4 mg + solifenacin 10 mg).

Group C Control (tamsulosin 0.4 mg + placebo).

PVR: post void residual urine volume; Q_aver: average flow rate; Q_max: maximum flow rate.

Standard deviation (SD) is indicated in parentheses.

p values >.05 in all cases (differences between groups are unreliable).

Procedure

The study was conducted in the urological department of the City Polyclinic No. 3 in Vladivostok, the Urological Department of the Gerontological Hospital and in Far Eastern Federal University from 1 March 2015 to 31 December 2015. All patients were assigned to group “A” (N = 93; tamsulosin 0.4 mg + solifenacin in a standard dose of 10 mg per day), group “B” (N = 83; tamsulosin 0.4 mg + solifenacin in a higher dose of 20 mg per day), and the control group C (N = 86; tamsulosin 0.4 mg + placebo) [27]. According to the study protocol, each patient was tested for the lower urinary tract (LUT), cognitive function and mental status, as well as HRQoL at the baseline and after the study (8 weeks later) (Figure 1). The study was conducted in compliance with the standards prescribed by the Helsinki Declaration and approved by the local ethics committee.

Figure 1. Scheme of examination and treatment of patients with BPH and OAB (N = 273). Remark: I-PSS: International Prostate Symptom Score; OAB-AT: Over Active Bladder Awareness Tool; MMSE: Mini-Mental State Examination; COWAT: Controlled Oral Word Association Test; WAIS-R: Wechsler Adult Intelligence Scale; WMS-III-test: Wechsler III; LM test: logical memory; CVLT: California Verbal Learning Test; SF-36-Medical Outcomes Study: 36-Item Short-Form.

Measures

Neurological assessment

To assess the functional state of the LUT, the following were used: the I-PSS (from 8 to 19 points – a moderate degree of impairment); questionnaire Over Active Bladder Awareness Tool (OAB-AT, OAB signs with an amount higher than 8 points); uroflowmetry.

Neuropsychological assessment

To screen for cognitive impairment, we used the MMSE. With the help of this tool, five areas of cognitive function were examined: orientation, registration, attention and calculation, recall and language. Verbal fluency was tested using the Controlled Oral Word Association Test (COWAT). The digit span test from the Wechsler Adult Intelligence Scale (WAIS-R, PL) was used to test the concentration of attention and reversing operation (mental double-tracking). The study of working memory and visual-spatial processing was carried out with the help of Wechsler III (WMS-III), short- and long-term organized verbal memory-using the logical memory (LM) test. The Color Trails Test (CTT) was used to assess the ability for visual search and adequate psychomotor responses. Finally, the California Verbal Learning Test (CVLT) served to measure verbal learning abilities and memory.

Assessment of HRQL

The HRQoL assessment was conducted using the Medical Outcomes Study 36-Item (MOS-36) Health Survey questionnaire. This questionnaire consists of eight independent scales: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health. Each of these scales has 4–6 levels. The total figure ranges from 0.30 to 1.0. The combination of domains examined by this tool is most sensitive to parameters that can be violated in individuals with BPH and OAB.

Statistical analysis

Information was processed using the program JMP SAS Statistical Discovery 8.0.2 (SAS Institute, Cary, NC). All results are presented as the mean ± standard deviation (SD) for continuous variables. The significance of the differences between the average indices of continuous variables with normal distribution was estimated by the Student’s t-test, the differences between the average distribution of variables were determined using the usual Mann–Whitney U-test. The Spearman coefficient was used to identify the relationship between the changes. Correlation within the range r = 0.6–1.0 was considered strong, r = 0.30–0.59 average, and r = 0.1–0.29 weak. Values of p < .05 were considered reliable and sufficient to recognize differences between samples.

Results

After treatment, the cognitive status of men from all three groups, including the control group, was not statistically different (Table 2). The cognitive function in all examined patients was in accordance with the norm. Cognitive function in patients taking solifenacin was reduced by a single recognition score obtained using the WMS 3 test (group A, B vs. group C: p < .05, p < .05).

Table 2. Descriptive statistics of the cognitive status, HRQoL and functional status LUT in men with BPH and OAB after treatment (N = 262).

	Group A (n = 93)	Group B (n= 83)	Group C (n= 86)	Cohen d A/C	Cohen d B/C
Parameters of cognitive status
Mini-Mental State Examination (MMSE)	28.2 (1.1)	27.9 (0.8)	29.1 (1.4)	0.32	0.34
Controlled Oral Word Association Test	13.6 (7.1)	14.5 (4.9)	13.5 (3.9)	0.63	0.58
Digit span forward (WAIS-R)	5.0 (1.1)	5.1 (1.4)	5.5 (1.6)	0.49	0.44
Digit span backward (WAIS-R)	3.9 (0.8)	4.5 (1.0)	4.7 (0.6)	0.43	0.41
The Color Trails Test 1 (CTT1)	60.4 (24.9)	66.8 (19.8)	53.6 (17.5)	−0.54	−0.61
The Color Trails Test 2 (CTT2)	121.5 (42.0)	143.5 (34.1)	113.7 (24.1)	−1.67	−1.51
Spatial span forward (WMS-3)	6.5 (1.5)	5.9 (1.7)	6.8 (1.7)	0.47	0.43
Spatial span backward (WMS-3)	6.7 (1.1)	7.1 (1.1)	7.0 (0.9)	0.57	0.48
Logic memory 1 recall (WMS 3)	35.3 (4.9)	33.5 (6.7)	37.8 (11.8)	0.58	0.49
Logic memory 2 recall (WMS 3)	19.5 (5.9)	19.1 (8.7)	21.9 (7.3)	0.42	0.53
Logic memory 2 recognition (WMS 3)	19.5 (4.3)*	20.8 (3.2)*	29.9 (3.3)	1.95	1.65
Logic memory 2 % retention (WMS 3)	84.6 (10.2)	80.1 (7.8)	86.0 (12.4)	0.34	0.29
California Verbal Learning Test TL	50.1 (5.9)	50.4 (7.1)	52.4 (8.4)	0.36	0.55
California Verbal Learning Test SDFR	8.8 (5.6)	9.7 (1.9)	11.6 (4.9)	0.39	0.41
California Verbal Learning Test SDCR	11.5 (5.3)	10.3 (2.9)	12.7 (5.7)	0.62	0.57
California Verbal Learning Test LDFR	10.8 (3.9)	10.8 (2.6)	12.0 (3.7)	0.56	0.50
California Verbal Learning Test LDCR	11.8 (2.6)	10.6 (1.9)	11.9 (3.3)	0.51	0.46
Parameters of health-related quality of life
MOS-36 Vitality	55.6 (11.5)	67.8 (10.2)	51.7 (10.6)	0.78	0.80
MOS-36 Physical functioning	55.9 (8.8)	62.3 (11.8)*	39.8 (7.4)	0.87	0.94
MOS-36 Bodily pain	21.4 (9.6)	18.8 (8.4)	22.9 (12.9)	1.67	1.55
MOS-36 General health perceptions	67.3 (10.5)*	81.5 (8.9)**	44.8 (9.0)	0.92	1.23
MOS-36 Physical role functioning	60.5 (9.2)	67.8 (14.4)	50.3 (10.3)	0.69	0.59
MOS-36 Emotional role functioning	65.6 (5.6)**	89.5 (9.6)**	43.6 (8.4)	2.6	2.9
MOS-36 Social role functioning	72.5 (7.4)**	91.5 (11.3)**	41.9 (13.6)	2.7	3.11
MOS-36 Mental health	60.2 (8.5)	74.6 (7.8)*	45.6 (9.6)	0.9	1.40
Parameters of lower urinary tract status
Uroflowmetry PVR, ml	47.3 (13.7)	18.6 (12.6)**	60.9 (9.7)	0.71	1.37
Uroflowmetry Qaver, ml/s	21.5 (6.3)	20.6 (5.7)	17.7 (4.8)	0.63	0.66
OAB-AT Urgency incontinence	0.9 (0.7)	0.4 (0.4)*	2.0 (0.4)	0.67	1.13
OAB-AT Urgency	1.9 (0.7)	0.9 (0.5)*	2.5 (0.5)	0.63	1.04
IPSS Incomplete emptying	1.4 (0.9)	1.7 (0.5)	1.6 (1.1)	0.48	0.54
IPSS Weak stream	0.9 (1.3)	1.4 (1.1)	1.3 (0.6)	0.57	0.51

Remark: Group A (tamsulosin 0.4 mg + solifenacin 5 mg per day), Group B (tamsulosin 0.4 mg + solifenacin 10 mg), Group C Control (tamsulosin 0.4 mg + placebo).

Parameter values for the patient’s cognitive status scales and the functional state of the LUT are given in scores, HRQoL scales are in %, for uroflowmetry in units indicated in the table.

WAIS-R: Wechsler Adult Intelligence Scale-Revised; WMS-3: Wechsler Memory Scale 3; SDFR: short-delay free recall; SDCR: short-delay cued recall; LDFR: long-delay free recall; LDCD: long delay cued recall; MOS-36: Medical Outcomes Study 36-Item (MOS-36) Health Survey; OAB-AT: Over Active Bladder Awareness Tool; IPSS: International Prostate Symptom Score; PVR: post void residual (urine volume).

*< 0.05, **< 0.01 – value p for groups A/C and B/C.

Statistically significant differences were found in the perception of the quality of life between groups A, B on the one hand, and group C on the other. Emotional and social role functioning in groups A and B did not differ, although in both groups it was significantly better than in group C, that is, in men who did not take solifenacin (p < .01; p < .01). General health perceptions in men taking solifenacin were also better than in the control group (p < .05 for A/C comparison, and p < .01 for B/C comparison). Physical functioning and mental health after treatment were evaluated as better only by those taking solifenacin in a higher dose (B/C: p < .05; p < .05). In patients taking the higher dosages of solifenacin, compared with the control group, the post-void residual urine volume (p < .01), the number of urgencies (p < .05), and urgency incontinence (p < .05) were significantly lower.

Table 3 shows the results of the study of the correlation of HRQoL domains with the parameters of the state of cognitive functions and the functional state of the LUT. According to the results, there was no correlation between the cognitive functions and HRQoL parameters. The exception was the average degree of interrelation found between CTT2 and general health perceptions (GHP) as well as emotional role functioning (ERF) in group B. At the same time, many HRQoL indicators negatively correlated with the functional state of the LUT. In groups A and B, the negative correlation between the level of GHP, ERF and social role functioning (SRF) on the one hand, and such parameters of the LUT state as post void residual (PVR), urge urinary incontinence (UUI) and urge urinary on the other ranged from r = −0.31 to −0.90 (p < .05). The HRQoL status parameter PVR correlated with physical functioning and mental health, r = −0.34; −0.30 (p < .05; p < .05). In group C, there was no correlation between the HRQoL and the LUT. Correlation between the parameters obtained using the IPSS and HRQoL questionnaire was also not found in any of the groups.

Table 3. The relationship between assessment of the health-related quality of life, level of cognitive performance and the symptoms of lower urinary tract after treatment by solifenacin.

	Health-related quality of life markers
	PF			GHP			ERF			SRF			MH
	Groups			Groups			Groups			Groups			Groups
Cognitive markers	A	B	C	A	B	C	A	B	C	A	B	C	A	B	C
Cognitive markers
MMSE	0.24	0.14	0.17	0.11	0.21	0.27	0.09	0.24	0.29	0.26	0.21	0.17	0.13	0.28	0.23
COWAT	0.20	0.19	0.28	0.18	0.26	0.23	0.22	0.24	0.29	0.11	0.23	0.25	0.17	0.27	0.20
WAIS-R f	0.21	0.11	0.03	0.21	0.21	−0.24	0.09	0.13	0.18	0.07	0.19	0.14	0.13	0.26	0.23
WAIS-R b	0.25	0.08	0.16	0.14	0.27	0.20	0.23	0.11	0.22	0.24	0.18	0.17	0.02	0.12	0.31
CTT1	0.13	0.13	0.19	0.27	0.20	0.15	0.11	0.18	−0.08	0.21	0.26	0.05	0.13	0.29	0.15
CTT2	0.24	0.26	0.17	0.14	0.45*	0.31	0.18	0.41*	−0.21	0.20	0.28	0.19	0.14	0.16	0.25
LM 2R	0.21	0.11	0.16	0.15	0.22	0.27	0.13	0.21	0.28	0.23	0.24	0.17	0.18	0.24	0.14
CVLT TL	0.22	0.23	0.12	0.13	0.11	0.21	0.12	0.27	0.21	−0.17	−0.10	−0.20	0.14	0.22	0.12
Urodynamic markers
PVR	−0.34	−0.34*	−0.14	−0.31*	−0.80*	−0.27	−0.55*	−0.64*	−0.11	−0.55*	−0.90*	−0.17	−0.26	−0.30*	−0.05
OAB UI	−0.14	−0.29	−0.07	−0.29	−0.61*	−0.11	−0.45*	−0.54*	−0.13	−0.71*	−0.56	−0.19	−0.21	−0.31*	−0.03
OAB U	−0.25	−0.25	−0.09	−0.37*	−0.58*	−0.13	−0.49*	−0.71*	−0.19	−0.39*	−0.66	−0.28	−0.23	−0.28	−0.18
IPSS IE	−0.28	−0.11	−0.16	−0.25	−0.27	−0.20	−0.35	−0.25	−0.15	−0.28	−0.22	−0.13	−0.17	−0.28	−0.23
IPSS WS	−0.24	−0.12	−0.19	−0.21	−0.31*	−0.15	−0.39	−0.24	−0.09	−0.30	−0.29	−0.24	−0.22	−0.28	−0.20

Remark: Spearmen coefficient (*p < .05, 95% correlation limits).

MMSE: Mini-Mental State Examination; COWAT: Controlled Oral Word Association Test; WAIS-R f: digit span forward; WAIS-R b: digit span backward; CTT1: Color Trails Test 1; CTT2: Color Trails Test 2; LM 2 R: Logic memory 2 recognition (WMS 3); CVLT TL: California Verbal Learning Test TL; PF: physical functioning; GHP: general health perceptions; ERF: emotional role functioning; SRF: social role functioning; MH: mental health; PVR: post void residual (urine volume). OAB U AT U, UT: overactive bladder awareness tool, urgency, urgency incontinence; IPSS IE: incomplete emptying; IPSS WS: weak stream.

Table 4 shows the results of the study of the correlation of cognitive markers and the LUT parameters. As can be seen from the presented data, there is no correlation between most markers of cognitive functions and state parameters of the LUT. The correlation of the average degree between CTT2, as well as PVR and U-OAB (r = −0.34, −0.41 (p < .05, p < .05) was noted in group B. The level of parameters of the cognitive status of patients before and after treatment was statistically homogeneous (Figure 2). Linear regressions confirmed the connection between most HRQoL indicators and the functional state of the LUT, as well as its absence between the cognitive status state, HRQoL, and the LUT state (not shown).

Figure 2. The relationship between assessment of level of cognitive performance before and after of treatment. Remark: WAIS-R F: digit span forward; WAIS-R B: digit span backward; COWAT: Controlled Oral Word Association Test; LM 2R: logic memory 2 recognition (WMS 3); MMSE: Mini-Mental State Examination; CVLT TL: California Verbal Learning Test TL; CTT1: Color Trails Test 1.

Table 4. The relationship between assessment of the level of cognitive performance and the symptoms of lower urinary tract.

	Urodynamic markers
	PVR			OAB UI			OAB U			IPSS IE			IPSS WS
	Groups			Groups			Groups			Groups			Groups
Cognitive markers	A	B	C	A	B	C	A	B	C	A	B	C	A	B	C
MMSE	−0.23	−0.18	−0.18	−0.14	−0.12	−0.41	−0.16	−0.12	−0.27	−0.29	−0.12	−0.24	−0.22	−0.40	−0.25
COWAT	−0.09	−0.16	−0.17	−0.26	−0.28	−0.21	−0.13	−0.15	−0.23	−0.22	−0.14	−0.14	−0.08	−0.06	−0.24
WAIS-R f	−0.24	−0.28	−0.26	−0.23	−0.16	−0.20	−0.20	−0.14	−0.05	−0.19	−0.21	−0.12	−0.26	−0.11	−0.12
WAIS-R b	−0.13	−0.14	−0.22	−0.10	−0.24	−0.27	−0.22	−0.23	−0.25	−0.13	−0.16	−0.22	−0.23	−0.27	−0.20
CTT1	−0.09	−0.06	−0.26	−0.27	−0.22	−0.14	−0.12	−0.28	−0.10	−0.14	−0.26	−0.21	−0.21	−0.30	−0.07
CTT2	−0.11	−0.34*	−0.24	−0.26	−0.19	−0.17	−0.26	−0.41*	−0.31	−0.21	−0.12	−0.14	−0.27	−0.21	−0.25
LM 2R	−0.21	−0.28	−0.24	−0.24	−0.20	−0.21	−0.23	−0.18	−0.17	−0.15	−0.16	−0.19	−0.21	−0.11	−0.13
CVLT TL	−0.13	−0.20	−0.17	−0.10	−0.15	−0.19	−0.15	−0.17	−0.16	−0.32	−0.13	−0.18	−0.07	−0.13	−0.18

Remark: Spearmen coefficient (*p<.05, 95% correlation limits).

MMSE: Mini-Mental State Examination; COWAT: Controlled Oral Word Association Test; WAIS-R f: digit span forward; WAIS-R b: Digit span backward; CTT1: Color Trails Test 1; CTT2: Color Trails Test 2; LM 2 R: Logic memory 2 recognition (WMS 3); CVLT TL: California Verbal Learning Test TL; PVR: post void residual (urine volume); OAB U AT U, UT: overactive bladder awareness tool, urgency, urgency incontinence; IPSS IE: incomplete emptying; IPSS WS: weak stream.

During the study, four patients from group A (4.3%), two patients from group B (2.4%) and one (1.2%) patient from group C ceased to participate. In group A, intolerable dry mouth (two people), acute exacerbation of chronic diseases (two patients) was the reason for the termination of therapy. In group B, the exacerbation of chronic diseases of the cardiovascular system in both cases was the cause of discontinuation of therapy. In group C, the cause of treatment discontinuation of the patient was the symptoms of digestive disorders.

Discussion

Solifenacin is the drug of choice for the treatment of OAB, the symptoms of which are often associated with BPH. These annoying, irritating symptoms can significantly affect HRQoL in men. Previously, it was found that solifenacin is effective and safe in the treatment of BPH with symptoms of OAB [26]. However, it is known that some AMs are capable of causing cognitive dysfunction in some patients, and some researchers point to the need for their careful use, especially in the elderly people [29]. In the literature, there are few data indicating that the combination of tamsulosin and solifenacin in a standard dosage does not change the cognitive status of men. Nevertheless, an evaluation of the effect of tamsulosin and the higher dosage of solifenacin on cognitive status and HRQoL has not been conducted previously. In our study, we tried to investigate these issues.

The functional state of the LUT at the end of the observation was significantly different between group C (control) and groups A and B. In the groups of patients taking different doses of solifenacin, no statistically significant differences between the majority of parameters were observed. When comparing the indicators of cognitive status between the groups at the start and at the finish of the study, no significant differences were found. Also, there were no significant differences in the values of cognitive parameters in each of the groups before and after treatment.

During the study of HRQoL, after the treatment completion, it was possible to find out that the emotional and social role functioning, as well as general health perceptions of patients from groups A and B have improved significantly. At the same time, physical functioning and mental health significantly improved only in individuals taking solifenacin in the higher dosage. During the study of the functional state of the LUT, we found that the parameters corrected by solifenacin administration (residual urine volume, imperative urges, urgency incontinence) in group B (higher dosage of solifenacin) were significantly better than in the other groups. According to the correlation regression analysis, there was no correlation between the parameters of HRQoL and cognitive function between the high and medium levels. Also, there was no correlation between the cognitive function parameters and the LUT state. Perhaps the lack of correlation can be explained by the stable state of cognitive functions, while the state of LUT and HRQoL has significantly improved under the influence of treatment. However, we noted the correlation between the average and strong level (r = −0.31 to −0.90, p < .05) between the urodynamic state markers and HRQoL parameters.

It is known that AMs can potentially affect the nervous system, including by causing cognitive impairment, especially in the elderly people. Negative effects of AMs are usually associated with the influence profile on the muscarinic receptor, lipophilicity, the ability to overcome the blood-brain barrier [29]. In a recent study, AM therapy is associated with a decline in cognitive function, namely worsening of semantic memory/language and executive function. However, in this study, despite the release of selective and non-selective AMs, no separate analysis of each AM is performed. Meanwhile, it is known that the effect of different AMs on the nervous system is different. The safety of solifenacin in a standard dosage (5 mg per day) for cognitive function in the elderly people is considered proven. In our study, we increased the dosage by half, assuming that the level of load on the central nervous system of this drug will remain unchanged, which was confirmed by the results obtained.

The efficacy of solifenacin on OAB symptoms in patients with BPH in this study was consistent with the results we obtained earlier. Between HRQoL patients and the level of OAB symptoms, a negative correlation was found between the mean and high levels, which are in good agreement with the data of other authors on the relationship between the severity of LUT and HRQoL symptoms [30]. Nevertheless, this pattern was first confirmed by us for a specific group of patients with BPH and OAB.

The limitation of our study lies in a relatively small sample size, which is due to the fact that it was aimed at a group with a high level of homogeneity. We also excluded depressed people from the sample, given that the small sample size could lead to incorrect data in the HRQoL study. We also limited the study to only one representative of a number of AM, which can be corrected in future work.

Conclusion

Administration of higher doses of solifenacin simultaneously with tamsulosin causes no effect on the cognitive abilities of BPH patients with OAB symptoms. Administration of higher doses of solifenacin in men with BPH leads to a significant increase in the therapeutic effect and quality of life associated with health. The increase in HRQoL correlates with the functional state of the LUT but is not correlated with the state of cognitive status.

Administration of higher doses of solifenacin simultaneously with tamsulosin is an effective and safe method of correcting BPH with OAB symptoms, which is accompanied by an increase in HRQoL. The combination of solifenacin in a double dosage and tamsulosin can be recommended for elderly BPH patients with OAB symptoms.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Disclosure statement

Authors claim there are no any conflicts of interest between them or against outside organizations.

Funding

This research was funded by the authors at their own expense.