Association Between Common Infections and Incident Post-Stroke Dementia: A Cohort Study Using the Clinical Practice Research Datalink

Figures & data

Figure 1 Flowchart of study participants.

Table 1 Characteristics of Study Participarticipants

	Total	No Infection	Any GP-Recorded Infection After Stroke*
			0–3 Months	3 Months–1 Year	1–5 Years
Baseline, N (%)
All patients	60,392 (100.0)	39,423 (65.3)	3590 (5.9)	6886 (11.4)	10,493 (17.4)
Mean age (SD)	72.6 (12.7)	71.7 (12.9)	76.4 (11.9)	75.4 (12.1)	72.7 (12.1)
Sex
Male	30,912 (51.2)	21,454 (54.4)	1523 (42.4)	3037 (44.1)	4898 (46.7)
Female	29,480 (48.8)	17,969 (45.6)	2064 (57.6)	3849 (55.9)	5595 (53.3)
Country
England	45,464 (75.6)	29,892 (75.8)	2700 (75.2)	5290 (76.8)	7772 (74.1)
Wales	5736 (9.5)	3616 (9.2)	324 (9.0)	659 (9.6)	1137 (10.8)
Scotland	7075 (11.7)	4767 (12.1)	401 (11.2)	692 (10.0)	1217 (11.6)
Northern Ireland	1927 (3.2)	1148 (2.9)	165 (4.6)	247 (3.6)	367 (3.5)
Ethnicity
White	43,526 (72.1)	28,300 (71.8)	2580 (71.9)	5069 (73.6)	7577 (72.2)
South Asian	885 (1.5)	593 (1.5)	50 (1.4)	88 (1.3)	154 (1.5)
Black	543 (0.9)	404 (1.0)	19 (0.5)	47 (0.7)	73 (0.7)
Other/Mixed	520 (0.9)	392 (1.0)	16 (0.5)	46 (0.7)	66 (0.6)
Unknown	14,918 (24.7)	9734 (24.7)	925 (25.7)	1636 (23.8)	2623 (25.0)
Local area deprivation score (quintiles)
1 (= least deprived)	10,787 (17.9)	6844 (17.4)	708 (19.7)	1277 (18.5)	1958 (18.7)
2	10,638 (17.6)	6935 (17.6)	634 (17.7)	1228 (17.8)	1841 (17.6)
3	12,564 (20.8)	8252 (20.9)	711 (19.8)	1447 (21.0)	2154 (20.5)
4	12,876 (21.3)	8772 (22.3)	711 (19.8)	1293 (18.8)	2100 (20.0)
5 (= most deprived)	13,527 (22.4)	8620 (21.9)	826 (23.0)	1641 (23.8)	2440 (23.3)
Smoking status
Never	21,273 (36.0)	14,026 (36.6)	1221 (34.2)	2360 (34.9)	3666 (35.1)
Past	25,936 (44.0)	16,396 (42.8)	1729 (48.4)	3156 (46.7)	4694 (45.0)
Current	11,884 (20.0)	7899 (20.6)	623 (17.4)	1249 (18.5)	2073 (19.9)
Alcohol Use (n=54,316)
None	15,287 (28.1)	9343 (26.7)	1067 (32.4)	2038 (32.8)	2839 (29.1)
Current	39,029 (71.9)	25,708 (73.3)	2231 (67.7)	4176 (67.2)	6914 (70.9)
BMI category
Underweight	1645 (3.0)	1031 (2.9)	132 (4.0)	213 (3.4)	269 (2.7)
Normal Weight	18,455 (33.9)	12,007 (34.3)	1172 (35.5)	2124 (34.0)	3152 (32.1)
Overweight	20,359 (37.4)	13,297 (38.0)	1180 (35.7)	2231 (35.7)	3651 (37.2)
Obese	13,941 (25.6)	8703 (24.8)	820 (24.8)	1684 (26.9)	2734 (27.9)
Clinical conditions
History of Diabetes	8978 (14.9)	5431 (13.8)	683 (19.0)	1224 (17.8)	1640 (15.6)
History of Atrial fibrillation	7995 (13.2)	4704 (11.9)	609 (17.0)	1186 (17.2)	1496 (14.3)
History of Myocardial Infarction	4831 (8.0)	2897 (7.4)	366 (10.2)	647 (9.4)	921 (8.8)
History of Depression	3697 (6.1)	2050 (5.2)	348 (9.7)	564 (8.2)	735 (7.0)
Use of medication in 2 years prior to stroke
Anti-hypertensive	35,781 (59.3)	22,077 (56.0)	2541 (70.8)	4581 (66.5)	6582 (62.7)
Statin	21,837 (36.2)	13,482 (34.2)	1531 (42.7)	2799 (40.7)	4025 (38.4)
Immunosuppressant	6894 (11.4)	3491 (8.9)	726 (20.2)	1308 (19.0)	1369 (13.1)
Post stroke, N (%)
Antiplatelet use within 90 days	37,148 (61.5)	23,792 (60.4)	2341 (65.2)	4223 (61.3)	6792 (64.7)
New depression post stroke±	5457 (9.6)	2885 (7.7)	383 (11.8)	821 (13.0)	1368 (14.0)

Notes: *Defined as any of lower respiratory tract infection, urinary tract infection with antibiotics, or skin/soft tissue infection with antibiotics. Timing is categorised by first infection after stroke. ± N=56,695.

Table 2 Rates of Early and Late Post-Stroke Dementia by Infection Status, and Results from Cox Regression Models

Infection		Total Dementia Cases	Total Person Time	Rate per 1000 Person Years (95% CI)	HR (95% CI)
					Crude	Sex and Age Adjusted	Fully Adjusted*	P-value **
Early Dementia
All	GP-recorded infections only
	No Infection	1145	35,284	32.45 (30.63–34.39)	1	1	1	<0.001
	Any Infection	261	4735	55.12 (48.83–62.23)	1.80 (1.57–2.06)	1.44 (1.26–1.65)	1.44 (1.21–1.71)
Restricted to patients with linked HES	GP recorded infections only
	No Infection	877	22,657	38.71 (36.23–41.36)	1	1	1	<0.001
	Any Infection	214	3011	71.07 (62.16–81.26)	1.93 (1.66–2.25)	1.57 (1.34–1.82)	1.53 (1.28–1.84)
	GP recorded and hospital recorded infections
	No Infection	581	19,052	30.50 (28.11–33.08)	1	1	1	<0.001
	Any Infection	510	6616	77.08 (70.67–84.07)	2.59 (2.30–2.91)	1.99 (1.76–2.24)	1.84 (1.58–2.14)
	GP recorded and hospital recorded infections where infection was primary diagnosis
	No Infection	775	21,778	35.59 (33.17–38.18)	1	1	1	<0.001
	Any Infection	316	3891	81.22 (72.74–90.69)	2.40 (2.11–2.74)	1.91 (1.67–2.18)	1.79 (1.52–2.11)
Late Dementia
All	GP recorded infections only
	No Infection	2009	84,239	23.85 (22.83–24.92)	1	1	1	0.296
	Any Infection	1097	36,150	30.35 (28.60–32.20)	1.30 (1.20–1.40)	1.07 (0.99–1.15)	1.05 (0.96–1.16)
Restricted to patients with linked HES	GP recorded infections only
	No Infection	1562	53,194	29.36 (27.94–30.86)	1	1	1	0.065
	Any Infection	847	22,121	38.29 (35.29–40.96)	1.31 (1.21–1.43)	1.09 (1.00–1.19)	1.10 (0.99–1.22)
	GP recorded and hospital recorded infections
	No Infection	955	43,680	21.86 (20.52–23.30)	1	1	1	<0.001
	Any Infection	1454	31,635	45.96 (43.66–48.39)	2.13 (1.96–2.31)	1.66 (1.53–1.80)	1.50 (1.35–1.66)
	GP recorded and hospital recorded infections where infection was primary diagnosis
	No Infection	1269	49,488	25.64 (24.27–27.09)	1	1	1	<0.001
	Any Infection	1140	25,827	44.14 (41.65–46.78)	1.75 (1.61–1.90)	1.40 (1.29–1.52)	1.36 (1.23–1.50)

Notes: *Adjusted for age, sex, country, consultation frequency, ethnicity, deprivation, alcohol, smoking, BMI, pre-morbid conditions, pre-stroke use of medication, anti-coagulant prescribing post stroke and depression (pre and post stroke). **Likelihood ratio test.

Table 3 Rates of Dementia by Number of Infections, and Results from Cox Regression Models

Infection		Total Dementia Cases	Total Person Time	Rate per 1000 Person Years (95% CI)	HR (95% CI)			P-value **
					Crude	Sex and Age Adjusted	Fully Adjusted*
Early Dementia
All	GP-recorded infections only
	No Infection	1145	35,284	32.45 (30.63–34.39)	1	1	1	0.0002
	1 infection	211	3851	54.79 (47.88–62.71)	1.77 (1.52–2.05)	1.44 (1.24–1.67)	1.48 (1.23–1.78)
	2 or more infections	50	884	56.57 (42.87–74.63)	1.94 (1.46–2.58)	1.43 (1.07–1.90)	1.26 (0.88–1.82)
Restricted to patients with linked HES	GP recorded infections only
	No Infection	877	22,658	38.71 (36.23–41.36)	1	1	1	<0.001
	1 infection	175	2453	71.35 (61.52–82.74)	1.92 (1.63–2.26)	1.58 (1.34–1.86)	1.59 (1.31–1.92)
	2 or more infections	39	559	69.83 (51.02–95.58)	1.99 (1.44–2.75)	1.50 (1.09–2.07)	1.31 (0.89–1.94)
	GP recorded and all hospital infections
	No Infection	581	19,052	30.50 (28.11–33.08)	1	1	1	<0.001
	1 infection	305	4673	65.28 (58.35–73.03)	2.17 (1.89–2.49)	1.69 (1.47–1.95)	1.57 (1.32–1.87)
	2 or more infections	205	1944	105.46 (91.97–120.93)	3.65 (3.11–4.28)	2.71 (2.31–3.19)	2.53 (2.06–3.11)
	GP recorded and primary hospital infections
	No Infection	775	21,778	35.59 (33.17–39.18)	1	1	1	<0.001
	1 infection	230	3051	75.38 (66.24–85.78)	2.21 (1.90–2.56)	1.78 (1.54–2.07)	1.69 (1.41–2.02)
	2 or more infections	86	840	102.43 (82.92–126.54)	3.18 (2.54–3.99)	2.38 (1.90–2.99)	2.16 (1.64–2.84)
Late Dementia
All	GP recorded infections only
	No Infection	2009	84,239	23.85 (22.83–24.92)	1	1	1	0.023
	1 infection	572	20,900	27.37 (25.22–29.71)	1.16 (1.06–1.28)	1.00 (0.91–1.10)	1.01 (0.90–1.14)
	2 infections	232	7729	30.02 (26.39–34.14)	1.29 (1.12–1.48)	1.03 (0.90–1.18)	1.03 (0.87–1.21)
	3 infections	126	3402	37.03 (31.10–44.10)	1.60 (1.34–1.92)	1.23 (1.03–1.47)	1.16 (0.93–1.45)
	4 infections	61	1668	36.58 (28.46–47.01)	1.59 (1.23–2.06)	1.20 (0.93–1.54)	0.97 (0.69–1.35)
	5 or more infections	106	2451	43.24 (35.74–52.31)	1.91 (1.56–2.32)	1.41 (1.16–1.72)	1.40 (1.11–1.77)
Restricted to patients with linked HES	GP recorded infections only
	No Infection	1562	53,194	29.36 (27.94–30.86)	1	1	1	0.002
	1 infection	428	12,783	33.48 (30.46–36.81)	1.15 (1.03–1.28)	1.00 (0.90–1.12)	1.05 (0.93–1.19)
	2 infections	187	4762	39.27 (34.03–45.32)	1.35 (1.16–1.58)	1.09 (0.93–1.27)	1.05 (0.88–1.26)
	3 infections	100	2107	47.46 (39.01–57.74)	1.65 (1.34–2.02)	1.27 (1.03–1.55)	1.25 (0.99–1.57)
	4 infections	44	1009	43.61 (32.45–58.60)	1.52 (1.12–2.05)	1.14 (0.85–1.55)	1.02 (0.72–1.45)
	5 or more infections	88	1460	60.28 (48.91–74.28)	2.11 (1.69–2.62)	1.57 (1.26–1.95)	1.55 (1.22–1.97)
	GP recorded and all hospital infections
	No Infection	955	43,680	21.86 (20.52–23.30)	1	1	1	<0.001
	1 infection	606	16,527	36.67 (33.86–39.71)	1.70 (1.53–1.88)	1.40 (1.26–1.55)	1.28 (1.13–1.45)
	2 infections	366	7220	50.69 (45.75–56.16)	2.37 (2.10–2.67)	1.78 (1.58–2.01)	1.70 (1.47–1.96)
	3 infections	186	3480	53.45 (46.29–61.71)	2.52 (2.15–2.95)	1.86 (1.59–2.18)	1.53 (1.26–1.86)
	4 infections	110	1774	62.03 (51.45–74.77)	2.94 (2.41–3.59)	2.09 (1.71–2.55)	1.88 (1.48–2.38)
	5 or more infections	186	2634	70.61 (61.16–81.53)	3.41 (2.90–4.00)	2.44 (2.08–2.86)	2.22 (1.84–2.70)
	GP recorded and primary hospital infections
	No Infection	1269	49,488	25.64 (24.27–27.09)	1	1	1	<0.001
	1 infection	539	14,345	37.58 (34.53–40.80)	1.49 (1.34–1.64)	1.25 (1.13–1.38)	1.27 (1.13–1.43)
	2 infections	262	5664	46.26 (40.98–52.21)	1.84 (1.61–2.11)	1.44 (1.26–1.65)	1.31 (1.11–1.54)
	3 infections	145	2654	54.63 (46.42–64.29)	2.20 (1.85–2.61)	1.66 (1.39–1.97)	1.50 (1.22–1.85)
	4 infections	74	1271	58.23 (46.36–73.13)	2.35 (1.86–2.98)	1.71 (1.35–2.17)	1.71 (1.31–2.23)
	5 or more infections	120	1893	63.39 (53.01–75.81)	2.60 (2.15–3.15)	1.92 (1.58–2.32)	1.86 (1.50–2.32)

Notes: *Adjusted for age, sex, country, consultation frequency, ethnicity, deprivation, alcohol, smoking, BMI, pre-morbid conditions, pre-stroke use of medication, anti-coagulant prescribing post-stroke and depression (pre- and post-stroke). **Likelihood ratio test.