1. Outcomes of thrombolysis treatment in patients with dementia and acute ischemic stroke
A longitudinal cohort study from SveDem and Riksstroke, Swedish Dementia and Stroke Registries
Eva Zupanic, MD

2. Objectives
~10% of patients with first stroke have a pre-existing dementia.
Patients with dementia are postulated to have worse functional prognosis and increased mortality after stroke.
Clinical trials often exclude >80 years, thus a large proportion of patients pre-existing dementia.

3. IV thrombolysis (IVT) in dementia
Dementia is not a contraindication for thrombolysis in acute ischemic stroke (AIS).
AHA/ASA scientific statement: dementia patients may benefit from IVT, however, decisions should be made individually.
National Swedish Stroke Guidelines did not recommend IVT in patients >80 until 2014 (except in particular cases after careful consideration).
There is an inconsistency in use of thrombolytic agent alteplase:
it is not indicated in patients >80 according to the European Medicines Agency.
it is recommended in selected patients in this age range according to European stroke guidelines..
There is a deep-rooted fear of increased risk of cerebral hemorrhage (e.g. amyloid angiopathy, microbleeds), however, increased incidence of symptomatic intracranial hemorrhage (sICH) has so far not been reported.
Stroke physicians might adopt a more conservative approach when treating patients with dementia and AIS.
taking into account clinically meaningful benefit, patients’ life expectancy and premorbid functional level

4. Methods Large nationwide cohort longitudinal study
Merge of two Swedish national quality registries:
SveDem, Swedish Dementia Registry
Riksstroke, Swedish Stroke Registry

5. Patient selection process
registrations in SveDem
excluded patients:
all strokes before dementia diagnosis
8963 matched controls from Riksstroke
2233 patients with stroke after dementia
3085 excluded patients:
previous strokes
stroke before 2010
hemorrhagic stroke
NON-DEMENTIA GROUP
6755 patients with ischemic stroke without dementia
DEMENTIA GROUP
1356 patients with dementia and subsequent first ischemic stroke

6. Characteristics of patients with dementia
DEMENTIA GROUP (n=1356)
Age at dementia diagnosis, median (IQR)
82 (9)
Age at stroke event, median (IQR)
83 (8)
Time from dementia dg to stroke dg in days, median (IQR)
546 (705)
MMSE at dementia dg, median (IQR)
21 (5)
MMSE groups, n (%) >24
354 (27.9)
20-24
525 (41.3)
<20
391 (30.8)
DEMENTIA TYPE, n (%): AD and mixed dementia
628 (46.3) VD
311 (22.9)
Other (LBD, FTD, PDD, unspecified, other)
417 (30.8)

7. Patients>80 years (n=5270)
Demographics, medication and comorbidities prior to stroke in patients with AIS
Patients≤80 years (n=2841)
Patients>80 years (n=5270)
WITH DEMENTIA
(n=436)
WITHOUT DEMENTIA
(n=2405)
p-value
(n=920)
(n=4350)
Age at first stroke, median (IQR)
77 (6)
76 (7)
0.190
86 (6)
0.871
Female sex
197 (45.2)
1124 (46.7)
0.550
567 (61.6)
2714 (62.4)
0.666
Nursing home placement
96 (22.3)
63 (2.6)
<0.001
327 (35.8)
441 (10.2)
Lives alone at home
119 (27.7)
896 (37.5)
327 (35.9)
2485 (57.4)
ADL-independent
262 (62.7)
2237 (93.7)
412 (48.0)
3548 (83.4)
No. of medication, median (IQR)
6 (5)
4 (5)
5 (5)
Antiaggregants
181 (41.5)
732 (30.4)
460 (50.0)
1768 (40.6)
Statins
107 (24.5)
543 (22.6)
0.369
139 (15.1)
797 (18.3)
0.021
Hypertension
222 (50.9)
1079 (44.9)
0.020
552 (60.0)
2402 (55.2)
0.008
Antihypertensives
272 (62.4)
1460 (60.7)
0.509
620 (67.4)
3080 (70.8)
0.040
Atrial fibrillation (AF)
108 (24.8)
449 (18.7)
0.003
345 (37.5)
1425 (32.8)
0.006
Warfarin in AF patients
24 (22.2)
101 (22.5)
0.951
29 (8.4)
241 (16.9)
Diabetes
445 (18.5)
0.002
165 (17.9)
729 (16.8)
0.388
Femur fracture
41 (9.4)
90 (3.7)
133 (14.5)
465 (10.7)
0.001
History of hemorrhage
61 (14.0)
210 (8.7)
126 (13.7)
479 (11.0)
Ischemic heart disease
105 (24.1)
230 (22.0)
0.346
267 (29.0)
1312 (30.2)
0.493
Heart failure
69 (15.8)
277 (11.5)
0.011
207 (22.5)
1001 (23.0)
0.737

8. Access to IVT

9. Patients > 80 years (n=5270)
Access to IVT
Patients ≤ 80 years (n=2841)
Patients > 80 years (n=5270)
WITH DEMENTIA
(n=436)
WITHOUT DEMENTIA
(n=2405)
p-value
(n=920)
(n=4350)
Thrombolysis
29 (6.7)
282 (11.8)
0.002
65 (7.1)
357 (8.2)
0.255

10. Model 3 (propensity scores)
Odds of receiving intravenous thrombolysis (IVT)
Comparison of patients with dementia and patients without dementia (reference category)
Thrombolysis performed
Model 1
Model 2
Model 3 (propensity scores)
All patients (n=8074)
0.73 ( )
0.68 ( )
0.72 ( )
≤80 years (n=2827)
0.55 ( )
0.51 ( )
0.53 ( )
>80 years (n=5247)
0.85 ( )
0.78 ( )
0.86 ( )
Only ADL-independent (n=6445)
0.85 ( )
0.74 ( )
0.83 ( )
≤80 years (n=2494)
0.63 ( )
0.60 ( )
0.58 ( )
>80 years (n=3951)
1.03 ( )
0.94 ( )
1.02 ( )
Name Surname
Odds ratios with 95% confidence intervals are reported.

11. Outcomes?

12. Outcomes after IVT
Out of 8111 patients, 9% (n=733) received thrombolysis
WITH DEMENTIA (n=94)
WITHOUT DEMENTIA
(n=639)
p-value
sICH
7 (7.4)
46 (7.3)
0.960
Inhospital death
12 (12.8)
85 (13.3)
0.886
mRS at 3 months
4 (4.9)
189 (33.2)
<0.001 3
20 (24.4)
155 (27.2)
0.592 4
12 (14.6)
66 (11.6)
0.425 5
28 (34.1)
53 (9.3)
(dead) 6
18 (22.0)
107 (18.8)
0.494
New nursing home placement
23 (35.9)
64 (13.6)

13. Model 4 (propensity scores)
Outcomes after IVT
Outcomes of thrombolysis
Model 1
Model 2
Model 3
Model 4 (propensity scores)
mRS at 3 months
5.63 ( )
3.49 ( )
3.65 ( )
4.67 ( )
Death at 3 months
1.06 ( )
0.83 ( )
0.71 ( )
1.03 ( )
New nursing home placement
3.19 ( )
3.83 ( )
4.39 ( )
3.29 ( )
Odds ratios with 95% confidence intervals are reported.

14. Conclusions
Younger patients with dementia were less likely to receive IVT.
The frequency of sICH, inhospital and 3-month mortality after IVT was similar in dementia and controls.
Among patients who received IVT, dementia was associated with greater disability and new nursing home placement.

15. Limitations Observational study  selection bias.
Patients who were not referred to hospitals were not included in the study, as Riksstroke does not cover out od hospital events.
In selected patients who do receive IVT, this procedure is safe with similar rates of complications.

16. Aknowledgements Project supervisior: Sara Garcia-Ptacek
Coauthors: Milica G. Kramberger, Mia von Euler, Bo Norrving, Bengt Winblad, Ingemar Kåreholt, Beatriz Contreras Escamez, Johan Fastbom, Dorota Religa, Kristina Johnell, Maria Eriksdotter
Home institution Department of Neurology, Ljubljana, Slovenia
Patients, families, health care providers, administrators, coordinators of SveDem and Riksstroke.
PROJECT‘S SPONSORS:
Johanniterorden
Foundation for research on diseases of aging at Karolinska Institutet
The Loo and Hans Osterman Medical Research Foundation
Swedish Stroke Association
Stohne’s Foundation
Foundation to the memory of Sigurd and Elsa Goljes