Stroke Identified as Independent Risk Factor for All-Cause Dementia

Elżbieta Kuźma, PhD, MSc, a research fellow in neuroepidemiology at the University of Exeter Medical School

Elżbieta Kuźma, PhD, MSc

Stroke has been identified as a strong, independent, and potentially modifiable risk factor for all-cause dementia, according to a newly published meta-analysis.

Ultimately, the results of an analysis of 40 clinical studies including almost 3 million patients revealed that the hazard ratio (HR) for all-cause dementia was 1.69 (95% CI, 1.49 to 1.92; P <.00001; I² = 87%; prediction interval [PI], 1.7 to 2.21) for prevalent stroke and the risk ratio for incident stroke was 2.18 (95% CI, 1.90 to 2.50; P <.00001; I² = 88%; PI, 1.67 to 2.69).¹

"We found that a history of stroke increases dementia risk by around 70%, and recent strokes more than doubled the risk,” Ilianna Lourida, PhD, a co-author and postdoctoral researcher at the University of Exeter, said in a statement.² “Given how common both stroke and dementia are, this strong link is an important finding. Improvements in stroke prevention and post-stroke care may, therefore, play a key role in dementia prevention."

These results were in line with previous research, including an analysis from Zhou J et al. which found a 59% increased risk of developing Alzheimer disease compared with controls,³ though this is the first to investigate the association between both prevalent and incident strokes with incident all-cause dementia.

Led by El&#380;bieta Ku&#378;ma, PhD, MSc, a research fellow in neuroepidemiology at the University of Exeter Medical School, the group of researchers assessed 46 studies in a systematic review, with 6 excluded from the meta-analysis. After finding the results, further sensitivity analysis excluding patients with mild cognitive impairment or combining stroke with transient ischemic attack (TIA) showed an essentially unchanged HRs of 1.71 (95% CI, 1.49 to 1.95; P <.001; I² = 89%; PI, 1.17 to 2.25) and 1.69 (95% CI, 1.46 to 1.96, P <.001; I² 5 51%, PI, 1.23 to 2.15), respectively.

Little evidence of effect modification was shown in meta-regression analysis, though some were identified in effect modification by sex. It revealed that the risk of dementia corresponding to prevalent stroke was higher in men than in women (P = .04), with the HR for men revealed to be 1.02 (95% CI, 1.00 to 1.03) compared to 0.98 (95% CI, 0.97 to 0.99) for women. "The reasons for this are unclear, and it could represent subtle biases in the original data or mechanisms that are currently unknown," David Llewellyn, PhD, MSc, a co-author and senior research fellow at the University of Exeter, told NeurologyLive.

"Stroke approximately doubles the risk of dementia, and stroke prevention and treatment should be prioritized when attempting to prevent dementia,” Llewellyn added. “Particular care should be taken to support the blood supply of middle-aged and elderly patients who are at risk for dementia. This could include the promotion of lifestyle factors such as physical activity and a Mediterranean diet which are risk factors for both stroke and dementia."

The authors did admit some limitations, most of which included the limitations included in the studies analyzed. For example, Ku&#378;ma and colleagues wrote, some studies included only one sex, volunteers, spouses of participants with stroke, and subsamples enrolled in specific projects. “Although most studies reported dementia-free participants at baseline, we cannot exclude the possibility that more studies than those already identified in our analysis included populations with MCI and cognitive impairment,” they wrote.

They also noted that not every study included was specifically designed to investigate the association between prevalent or incident stroke and dementia, and the timing of the development of dementia relative to the diagnosis makes it difficult to determine the exact time of dementia onset, though they noted that the stronger association shown for incident stroke suggests the risk is greater near the time of stroke manifestation. These limitations could have resulted in an overestimation of the association between all-cause dementia and stroke, though the robustness of the results to sensitivity analysis must be noted.

"For some time we have known that vascular factors in general and stroke, in particular, are important risk factors for dementia," Llewellyn said. "However, variation between studies meant that it wasn’t previously possible to quantify this risk. Furthermore, interest in vascular aspects of dementia has been growing and is now suspected to play a role in Alzheimer’s disease, not just vascular and mixed dementia."

REFERENCES

1. Ku&#378;ma E, Lourida I, Moore SF, et al. Stroke and dementia risk: a systematic review and meta-analysis. Alzheimer’s & Dementia. Epub 2018. doi: 10.1016/j.jalz.2018.06.3061

2. Stroke doubles dementia risk, concludes large-scale study [press release]. Exeter, UK: University of Exeter. Published August 31, 2018. eurekalert.org/emb_releases/2018-08/uoe-sdd082818.php. Accessed August 31, 2018.

3. Zhou J, Yu J-T, Wang H-F, Meng X-F, Tan C-C, Wang J, et al. Association between stroke and Alzheimer’s disease: Systematic review and meta-analysis. J Alzheimers Dis. 2015;43:479—89.