Heart Disease Linked to Impaired Cognition and Later Dementia
By Judith Groch
LONDON, 23 july 2008-- Coronary heart disease in midlife is associated with poorer results on cognitive tests, such as reasoning, vocabulary, and verbal fluency, with the effect particularly marked in men, a study found.
This "lifelong" view of developing dementia, which stresses the importance of risk factors in midlife, also found that the earlier in life heart disease was diagnosed, the worse the person's later cognitive performance, Archana Singh-Manoux, Ph.D., of University College London and INSERM in Villejuif Cedex, France, and colleagues reported in the European Heart Journal.
There is an increasing consensus that events in earlier life can have an impact on whether dementia develops in older age, Dr. Singh-Manoux said.
Until now, research on the association between coronary heart disease and dementia has focused more on cerebrovascular disease than on coronary heart disease, with emphasis on the elderly, the researchers said.
So the researchers examined the effect of the history and duration of coronary heart disease (including nonfatal myocardial infarction and definite angina) on cognition in a population with a mean age of 61.
Data come from the long-running Whitehall II study, begun in 1985, of 10,308 civil servants working in Whitehall London (33% women), ages 35 to 55 at baseline (1985-88).
Coronary heart disease events were assessed up to the 2002 to 2004 phase of the study when 5,837 participants (28.4% women) took six cognitive tests: verbal and mathematical reasoning, vocabulary, phonemic and semantic fluency, memory, and the mini-mental-state-examination (MMSE).
Results were standardized to T-scores (mean=50, standard deviation=10).
Analysis of covariance was used first to model the association between coronary heart disease history and cognition and then to examine the effect of time since a first heart event (in the preceding five years, five to 10 years previous, and more than 10 years previous).
Among men, compared with those with no history of coronary heart disease, analyses adjusted for age, education, marital status, and cardiovascular medication, having a history of coronary heart disease was associated with lower T-scores on reasoning (21.16, 95% confidence interval 22.07 to 20.25), vocabulary (22.11, 95% CI 23.01 to 21.21), and the MMSE (21.45, 95% CI 22.42 to 20.49).
In women, these effects were also evident for phonemic and semantic fluency (-2.85 and -1.75, respectively).
Among men, the trend within coronary heart disease cases suggested progressively lower scores on reasoning, vocabulary
and semantic fluency among those with a longer duration of heart disease.
Men whose first coronary event occurred more than 10 years before had lower scores on reasoning (22.94, 95% CI 24.35 to 21.52), vocabulary (23.58, 95% CI 25.00 to 22.16), semantic fluency (22.10, 95% CI 23.54 to 20.64), and the MMSE (21.84, 95% CI 23.35 to 20.32).
The test for trend and an examination of the effect for each five-year period among men suggests a trend for lower cognitive scores for verbal and mathematical reasoning and semantic fluency with increase in the time since a first cardiac event.
Among women, the association between time since the first event diagnosed 10 years earlier and cognitive performance showed a trend toward lower scores for semantic fluency. However, for this analysis, the numbers were small.
The prevalence of dementia rises with age, doubling every four to five years after the age of 60 so that over a third of those older than 80 are likely to have dementia, the researchers said.
Thus, although heart disease manifests itself in midlife, dementia occurs later in life. Increasingly, it is recognized that there is a long preclinical phase characterized by progressive neuropathological changes.
This suggests an association between coronary heart disease history and cognitive performance in middle-aged adults that is eventually recognized as cognitive deficit or dementia, the researchers said.
At this point the researchers said they cannot explain the pathophysiological pathway for their findings.
It is possible, they said, that shared risk factors drive this association or that impaired cognition or incipient dementia may in itself lead to coronary heart disease through poor health self-care.
Thus, they said, examining these associations in midlife or early older age offers some advantage over studying the elderly when other age-related conditions can obscure or confound the results.
Study limitations included the fact that all participants had stable white-collar jobs and were not representative of the general population. Despite the size of the study, it was underpowered especially for women, so that gender comparisons could not be made.
Also, the researchers said, missing data were likely to bias the results, leading to underestimation of the association between heart disease and cognition.
Finally, they said, the lack of baseline cognitive data prevented making causal inferences on the direction of the association.
It is important to emphasize, the researchers said, that major risk factors for coronary heart disease, such as smoking, diabetes, hypertension, hyperlipidemia, and lack of exercise are modifiable.
These findings of evolving risk show the importance of preventive strategies in highlighting these risk factors not only for coronary heart disease but also for cognitive outcome, the researchers concluded.
This "lifelong" view of developing dementia, which stresses the importance of risk factors in midlife, also found that the earlier in life heart disease was diagnosed, the worse the person's later cognitive performance, Archana Singh-Manoux, Ph.D., of University College London and INSERM in Villejuif Cedex, France, and colleagues reported in the European Heart Journal.
There is an increasing consensus that events in earlier life can have an impact on whether dementia develops in older age, Dr. Singh-Manoux said.
Until now, research on the association between coronary heart disease and dementia has focused more on cerebrovascular disease than on coronary heart disease, with emphasis on the elderly, the researchers said.
So the researchers examined the effect of the history and duration of coronary heart disease (including nonfatal myocardial infarction and definite angina) on cognition in a population with a mean age of 61.
Data come from the long-running Whitehall II study, begun in 1985, of 10,308 civil servants working in Whitehall London (33% women), ages 35 to 55 at baseline (1985-88).
Coronary heart disease events were assessed up to the 2002 to 2004 phase of the study when 5,837 participants (28.4% women) took six cognitive tests: verbal and mathematical reasoning, vocabulary, phonemic and semantic fluency, memory, and the mini-mental-state-examination (MMSE).
Results were standardized to T-scores (mean=50, standard deviation=10).
Analysis of covariance was used first to model the association between coronary heart disease history and cognition and then to examine the effect of time since a first heart event (in the preceding five years, five to 10 years previous, and more than 10 years previous).
Among men, compared with those with no history of coronary heart disease, analyses adjusted for age, education, marital status, and cardiovascular medication, having a history of coronary heart disease was associated with lower T-scores on reasoning (21.16, 95% confidence interval 22.07 to 20.25), vocabulary (22.11, 95% CI 23.01 to 21.21), and the MMSE (21.45, 95% CI 22.42 to 20.49).
In women, these effects were also evident for phonemic and semantic fluency (-2.85 and -1.75, respectively).
Among men, the trend within coronary heart disease cases suggested progressively lower scores on reasoning, vocabulary
and semantic fluency among those with a longer duration of heart disease.
Men whose first coronary event occurred more than 10 years before had lower scores on reasoning (22.94, 95% CI 24.35 to 21.52), vocabulary (23.58, 95% CI 25.00 to 22.16), semantic fluency (22.10, 95% CI 23.54 to 20.64), and the MMSE (21.84, 95% CI 23.35 to 20.32).
The test for trend and an examination of the effect for each five-year period among men suggests a trend for lower cognitive scores for verbal and mathematical reasoning and semantic fluency with increase in the time since a first cardiac event.
Among women, the association between time since the first event diagnosed 10 years earlier and cognitive performance showed a trend toward lower scores for semantic fluency. However, for this analysis, the numbers were small.
The prevalence of dementia rises with age, doubling every four to five years after the age of 60 so that over a third of those older than 80 are likely to have dementia, the researchers said.
Thus, although heart disease manifests itself in midlife, dementia occurs later in life. Increasingly, it is recognized that there is a long preclinical phase characterized by progressive neuropathological changes.
This suggests an association between coronary heart disease history and cognitive performance in middle-aged adults that is eventually recognized as cognitive deficit or dementia, the researchers said.
At this point the researchers said they cannot explain the pathophysiological pathway for their findings.
It is possible, they said, that shared risk factors drive this association or that impaired cognition or incipient dementia may in itself lead to coronary heart disease through poor health self-care.
Thus, they said, examining these associations in midlife or early older age offers some advantage over studying the elderly when other age-related conditions can obscure or confound the results.
Study limitations included the fact that all participants had stable white-collar jobs and were not representative of the general population. Despite the size of the study, it was underpowered especially for women, so that gender comparisons could not be made.
Also, the researchers said, missing data were likely to bias the results, leading to underestimation of the association between heart disease and cognition.
Finally, they said, the lack of baseline cognitive data prevented making causal inferences on the direction of the association.
It is important to emphasize, the researchers said, that major risk factors for coronary heart disease, such as smoking, diabetes, hypertension, hyperlipidemia, and lack of exercise are modifiable.
These findings of evolving risk show the importance of preventive strategies in highlighting these risk factors not only for coronary heart disease but also for cognitive outcome, the researchers concluded.
Primary source: European Heart JournalSource reference:Singh-Manoux A, et al "History of coronary heart disease and cognitive performance in midlife: the Whitehall II study" European Heart Journal 2008; DOI: 10.1093/eurheartj/ehn298.
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