Memory Issues Linked to Increased Stroke Risk

December 12, 2014

Subjective memory symptoms might be an early indicator of stroke risk, especially in highly educated people, a new study suggests.

"We found that individuals who said they were having memory losses had a 20% increased risk of stroke over the following 10 years, and this rose to 40% in those who were highly educated," senior author, Arfan Ikram, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, told Medscape Medical News.

"Memory complaints may be the first signs of vascular damage accumulating subclinically in the brain that can eventually lead to stroke," he added.

Dr Ikram pointed out that this is one of the first studies to look at the association between memory issues and subsequent stroke, so the results need confirmation. "But if they are confirmed I would recommend that people who are having memory losses which are really interfering with their lives should think about having a full cardiovascular evaluation, which will also flag stroke risk," he said.

Their findings were published online in Stroke on December 11.

First Manifestation of Vascular Abnormality

It is already known that patients who have had a stroke are at increased risk for cognitive impairment brought about by the death of brain cells caused by the stroke itself and also by the vascular damage leading up to the stroke, Dr Ikram explained.

"But we wanted to look at whether the reverse is also true: whether cognitive deficits predict stroke. We thought that this may be the case as the accumulation of vascular pathology that causes stroke may manifest itself as memory problems," he commented.

The study involved 9152 individuals older than age 55 years (average age, 67 years) and free of stroke or dementia living in one area of Rotterdam. They were asked the simple question, "Do you have memory complaints that interfere in your daily life?"

Dr Ikram notes, "Everybody forgets where they have put their keys sometimes, but we were asking about more serious memory complaints that interfered with the daily routine."

Participants also underwent objective cognitive testing with the Mini-Mental State Examination (MMSE).

They were then monitored for 10 years, and the occurrence of stroke was ascertained from automatic linkage of general practitioner files with the study database, as well as further follow-up of nursing home and hospital records.

The prevalence of subjective memory problems in the study population was 17%, which the authors say is similar to numbers in the literature for similar age groups.

Results showed a strong and significant association between those who had answered "yes" to the question of memory problems and future risk for stroke, after adjustment for many factors, including age, sex, cardiovascular risk factors, APOE ε4 allele carrier status, and measures of depression.

This risk was higher in participants with a higher level of education (higher vocational education or university training). In contrast, there was no association with the MMSE test result and stroke risk.

Table. Stroke Risk by Subjective and Objective Memory Measures

Analysis Hazard Ratio (95% Confidence Interval)
Subjective memory symptoms 1.20 (1.04 - 1.39)
Subjective memory symptoms in highly educated individuals 1.39 (1.07 - 1.81)
MMSE score (per point higher) 0.99 (0.95 - 1.02)


"We found the subjective measure was more informative of stroke risk than the objective test," Dr Ikram commented.

He suggested that this may because the MMSE test is not sensitive enough to pick up the information needed. "The MMSE is quite a crude measure. Maybe it just did not capture the right information. The subjective test may be better as it is one's own impression of memory. You tend to know yourself if you have memory issues."

In the paper, the researchers say the study outcome "supports our hypothesis that early vascular damage presenting as memory complaints, which are not yet evident in cognitive tests, may in future lead to clinical stroke."

Stronger Effect in the Highly Educated

Another interesting observation was that the association between subjective memory impairment and stroke risk appeared to be stronger in individuals who were highly educated.

On this, Dr Ikram said, "Education builds cognitive reserve — it produces a buffer against cognitive damage later in life. People with large cognitive reserve generally take longer to show signs of cognitive impairment and dementia as they cope better with accumulating vascular injury in the brain and can maintain their performance on cognitive testing. But these individuals may be more likely to notice subtle changes in their own memory, so subjective memory complaints in these highly educated persons might be a better marker than cognitive testing."

In the paper the authors recommend that "People with high level of education who complain about changes in their memory should be a primary target for further risk factor screening and prevention of stroke."

Dr Ikram acknowledged to Medscape Medical News that the simple question asked in this study is a limitation because it is very subjective. "Before making the transition to clinical practice we need to quantify the memory loss in some way. We could formulate a few more subtle questions to get a better idea of the problem, such as 'How often does this happen? How long has it been going on?'"

He also pointed out that better objective measures of early memory loss need to be developed. "We need to figure out what it is about the subjective measure that is not being picked up in the objective tests."

Dr Ikram noted that the researchers have MRI scans available for many of the participants and that a future analysis will examine whether the memory problems correlate with changes see on these scans.

The current study was supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Netherlands Genomics Initiative; the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission; and the Municipality of Rotterdam. The authors have disclosed no relevant financial relationships.

Stroke. Published online December 11, 2014. Abstract


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