Published: October 25, 2010
Heavy smoking in middle age may more than double the risk of Alzheimer's disease later in life, according to a large population-based study.
The prospective cohort study of more than 21,000 people found that those who smoked more than two packs a day developed dementia of any kind twice as often as nonsmokers, Rachel A. Whitmer, PhD, of Kaiser Permanente in Oakland, Calif., and colleagues reported.
The brain might not see the most immediate impact of smoking -- but isn't immune to its long-term effects, Whitmer and co-authors cautioned online in the Archives of Internal Medicine.
* Point out that as smoking data were collected only at midlife, the study cannot determine whether subsequent smoking cessation will reduce the dementia risk.
Smokers are more likely to die of other causes but shouldn't think they've gotten off scot-free if they don't have a heart attack or get lung cancer or emphysema, Whitmer noted in an interview monitored by a Kaiser Permanente media relations employee.
"If they've made it to late life and don't have respiratory disease or vascular disease, they need to know that their brain is also at risk," Whitmer told MedPage Today. "They need to know that there are long-term consequences."
The negative public health impact of smoking has the potential to become even greater as the population worldwide ages and dementia prevalence increases, she and her colleagues warned in their paper.
Tobacco's link with neurodegenerative or cognitive damage has been somewhat controversial, with some studies even suggesting a lower risk for smokers, Whitmer's group noted.
To get a handle on potential links between smoking and Alzheimer's disease (given its long preclinical phase), the researchers analyzed data from a multiethnic cohort of 21,123 individuals insured by Kaiser Permanente and surveyed as part of routine medical care between 1978 and 1985, when they were ages 50 to 60.
Over the next two to three decades (mean 23 years of follow-up), 25.4% of the study cohort received a diagnosis of dementia -- including 1,136 cases of Alzheimer's disease and 416 cases of vascular dementia.
Light or moderate smoking in middle age didn't appear to increase dementia risk in a direct linear fashion.
Rather, the risk of dementia jumped substantially to an age-adjusted 786.42 per 10,000 person-years once smoking topped two packs a day in mid-life -- producing a 2.14 fold higher risk (95% CI 1.65 to 2.78) than for nonsmokers in the fully-adjusted model.
The same was true for Alzheimer's disease risk, with a fully-adjusted risk 2.57 times higher for those who smoked more than two packs per day compared with nonsmokers (95% CI 1.63 to 4.03). The risk for vascular dementia was similar -- a 2.72-fold higher risk (95% CI 1.20 to 6.18) among heavy smokers.
The adjusted hazard ratio for dementia at lower levels of tobacco use when compared with nonsmokers was:
* 1.44 for one to two packs per day (95% CI 1.26 to 1.64)
* 1.37 for half to one pack per day (95% CI 1.23 to 1.52)
* A nonsignificant 1.04 for less than half a pack a day (95% CI 0.91 to 1.20)
* Not elevated for former smokers (HR 1.00, 95% CI 0.94 to 1.07)
None of those with less intense smoking habits or former smokers appeared to be at significantly increased risk of Alzheimer's disease or vascular dementia later in life -- but smoking less or quitting didn't seem to be protective either.
The researchers noted that the evaluation of smoking in middle age likely helped to reduce bias from falsely-recalled information or from the effect of subclinical dementia that might have been more of a concern in an elderly population.
But the study was limited by its use of medical records to determine dementia diagnoses and possible undiagnosed dementia in the cohort, Whitmer and colleagues cautioned. Moreover, the assessment of smoking only in middle age left it unclear whether quitting reduced dementia risk, they added.
Heavy smoking could have its impact on the brain via oxidative stress and inflammation -- both believed to be important in development of Alzheimer's disease -- or through vascular and neurodegenerative pathways, the investigators suggested.
However, the exact mechanism whereby smoking may lead to dementia still needs to be clarified, Whitmer's group concluded.
The study was supported by the National Graduate School of Clinical Investigation and by grants from Kuopio University Hospital, the Juho Vainio Foundation, Maire Taponen Foundation, a Kaiser Permanente Community Benefits, and National Institute of Health and Academy of Finland.
One of the authors reported having received honoraria for serving on the scientific advisory board of Elan and Pfizer and serving as a speaker on scientific meetings organized by Janssen, Novartis, and Pfizer.
Primary source: Archives of Internal Medicine
Source reference: Rusanen M, et al "Heavy smoking in midlife and long-term risk of Alzheimer disease and vascular dementia" Arch Intern Med 2010; DOI:10.1001/archinternmed.2010.393.
Reviewed by Zalman S. Agus, MD; Emeritus Professor, University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner