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Smoking Appears Linked With Risk for Poor Memory in Middle Age

  • Authors: News Author: Marlene Busko
    CME Author: Penny Murata, MD
  • CME/CE Released: 6/12/2008
  • Valid for credit through: 6/12/2009, 11:59 PM EST
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This article is intended for primary care clinicians, cardiologists, psychiatrists, neurologists, and other specialists who provide care to adults with a history of smoking.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Report whether smoking history is associated with cognitive function in middle-aged adults.
  2. Describe the risk for death and nonparticipation in cognitive tests among middle-aged adults who smoke.


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  • Marlene Busko

    Marlene Busko is a staff journalist for Medscape Psychiatry. She can be contacted at [email protected].


    Disclosure: Marlene Busko has disclosed no relevant financial relationships.


  • Brande Nicole Martin

    Brande Nicole Martin is the News CME editor for Medscape Medical News.


    Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

CME Author(s)

  • Penny Murata, MD

    Freelancer for Medscape


    Disclosure: Penny Murata, MD, has disclosed no relevant financial relationships.

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Smoking Appears Linked With Risk for Poor Memory in Middle Age

Authors: News Author: Marlene Busko CME Author: Penny Murata, MDFaculty and Disclosures

CME/CE Released: 6/12/2008

Valid for credit through: 6/12/2009, 11:59 PM EST


June 12, 2008 — Smoking is linked to an increased risk for memory deficit and cognitive decline in middle age in an analysis based on data from Whitehall II, a large, prospective cohort study.

The findings by Séverine Sabia, MSc, at the Institut National de la Santé et de la Recherche Médicale, in Villejuif, France, and colleagues, are published in the June 9 issue of the Archives of Internal Medicine.

Compared with study participants who had never smoked, after adjustment for other confounding factors, smokers had a 37% increased risk of having scores in the lowest quintile on a memory test (they were more likely to recall less than 5 of 20 words), Ms. Sabia told Medscape Psychiatry.

Cognitive Decline in Middle Age

"This risk is quite important considering that we are only in middle-age when cognitive decline is just starting," she noted. Evidence of this association at this age could support the hypothesis that smoking is involved in the pathogenesis of preclinical cognitive deficit and decline, which is a risk factor for later dementia, she added.

With the aging population and the projected increases in older adults with dementia, it is important to identify modifiable risk factors, she noted. "Our results suggest that smoking had an adverse effect on cognitive function in midlife, [but] 10 years after smoking cessation, there was little adverse effect of smoking on cognition," she added. "Thus, public health messages should target smokers at all ages."

A recent meta-analysis concluded that smoking is a risk factor for dementia, the group writes, adding that it is problematic to study the link between smoking and cognition (thinking, learning, and memory) in older people because many study participants do not return for follow-up visits, or they die from smoking-related diseases.

At the same time, there is increasing evidence that midlife risk factors play a role in later dementia.

Does Smoking Affect Memory?

The group aimed to investigate the association between smoking history and cognitive function in middle-aged individuals.

They analyzed data from the Whitehall II study, which was designed to examine the socioeconomic gradient in health and disease. Whitehall II enrolled 10,308 London-based civil servants (6895 men and 3413 women) aged 35 to 55 years at baseline (phase 1) from 1985 to 1988.

Cognition was assessed at phase 5, when participants were aged 45 to 68 years (mean age, 55.5 years) and 5 years later, at phase 7, when participants were aged 50 to 74 years (mean age, 61 years), said Ms. Sabia.

Cognitive data from tests of memory, reasoning, vocabulary, and semantic and phonetic fluency were available for 5388 participants at phase 5 and 4659 participants at phase 7.

Smoking was assessed at baseline and at phase 5. At baseline, the smokers smoked an average of 14 cigarettes a day; 25% were light smokers (≤ 5 cigarettes/day) and 25% were heavy smokers (1 - 2 packs/day), but only 27 participants smoked more than 2 packs/day, she noted.

Four Key Findings

The study presented 4 key findings, the group writes.

First, smoking in middle age was associated with memory deficit and decline in reasoning abilities. At phase 5, after adjustment for sex, age, socioeconomic differences, health behaviors, and health measures, current smokers vs participants who had never smoked had a 37% greater risk of being in the lowest quintile of cognitive function (odds ratio, 1.37; 95% confidence interval [CI], 1.10 - 1.73).

Second, compared with smokers, long-term ex-smokers (those who had stopped smoking before the beginning of the study) had a 30% lower risk for poor vocabulary and low verbal fluency.

Third, giving up smoking in midlife was accompanied by improvement in health habits such as drinking less alcohol, being more active, and eating more fruits and vegetables.

Fourth, compared with nonsmokers, smokers were more likely to die by phase 7 (an average 17.1 years of follow-up) or not to participate in cognitive tests, suggesting that nonparticipants had cognitive deficits and that, thus, the association between smoking and cognition in late midlife could be underestimated.

These findings are important because other research suggests that individuals with mild cognitive impairment progress to clinically diagnosed dementia at an accelerated rate, the group writes.

Not Too Late to Stop Smoking

"During the past 20 years, public health messages about smoking have led to changes in smoking behavior," they note. Based on the current study, "public health messages on smoking should continue to target smokers at all ages," they conclude.

This study was supported by the British Medical Research Council, the French Ministry of Research, and the European Science Foundation. The Whitehall II study was supported by the British Medical Research Council; the British Heart Foundation; the British Health and Safety Executive; the British Department of Health; the National Heart, Lung, and Blood Institute; the National Institute on Aging; the Agency for Health Care Policy and Research; and the John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health. Two of the study authors have obtained funding. The other study authors have disclosed no relevant financial relationships.

Arch Intern Med. 2008;168:1165-1173.

Clinical Context

A meta-analysis by Anstey and colleagues in the August 15, 2007, issue of the American Journal of Epidemiology found that smoking is a risk factor for dementia. However, as noted by Kukull in the February 1, 2001, issue of Biological Psychiatry, the effects of smoking might be difficult to determine because of attrition and smoking-related mortality before the diagnosis of dementia. However, the effects of smoking on cognitive ability before the onset of dementia could be examined.

In the Whitehall II study described by Marmot and colleagues in the June 8, 1991, issue of The Lancet, civil servants were recruited in 1985 to assess the link between socioeconomic factors and health. This study uses the Whitehall II database to examine whether smoking history is associated with cognitive function in middle-aged adults and to assess the risk for death and participation in cognitive tests in those who smoke.

Study Highlights

  • 10,308 civil servants aged 35 to 55 years enrolled in phase 1 from 1985 to 1988, which included clinical examination and survey regarding smoking habits.
  • Of 7830 who participated in phase 5 from 1997 to 1999, complete data were available for 5388 subjects.
  • 4659 participated in phase 7 from 2002 to 2004.
  • Mean follow-up was 17.1 years.
  • Smoking history categories were never-smoker, long-term ex-smoker who stopped before phase 1, recent ex-smoker who stopped between phases 1 and 5, and current smoker at phase 5.
  • Cognitive function testing occurred at phases 5 and 7:
    • Short-term verbal memory assessment by 20-word free recall test
    • Reasoning assessment by the Alice Heim AH4 Group Test of General Intelligence with use of verbal and mathematical reasoning items
    • Vocabulary assessment by Mill Hill Vocabulary Test
    • Phonemic and semantic verbal fluency
    • Results were adjusted for covariates:
    • Sociodemographics: age, sex, marital status, education, socioeconomic position
    • Health behaviors: alcohol use, fruit and vegetable intake, physical activity
    • Health measures at phase 5: coronary heart disease, stroke, diabetes mellitus, systolic and diastolic blood pressure, and serum cholesterol level
  • Increased smoking trend was linked to lower socioeconomic status, less education, greater alcohol use, less fruit and vegetable intake, and higher cholesterol level.
  • Characteristics not linked to smoking status included marital status, physical activity, coronary heart disease, stroke, diabetes mellitus, and blood pressure.
  • Phase 5 subject vs baseline group was younger (55.5 vs 56.1 years), had fewer women (27.6% vs 33.1%), and had fewer people of low socioeconomic status (14.6% vs 22.7%).
  • Adjusted risk for death was higher for current smokers at phase 1 vs never-smokers for men (hazard ratio [HR], 2.00; 95%, CI, 1.58 - 2.52) and women (HR, 2.46; 95% CI, 1.80 - 3.37).
  • Risk for death was not higher for ex-smokers at phase 1 vs never-smokers.
  • Likelihood of not participating in cognitive tests was higher for current smokers at phase 1 vs never-smokers for men (OR, 1.32; 95% CI, 1.16 - 1.51) and women (OR, 1.69; 95% CI, 1.41 - 2.02).
  • Adjusted results for cognitive deficits at phase 5:
    • Current smokers vs never-smokers had memory deficit (OR, 1.37; 95% CI, 1.10 - 1.73; P < .05).
    • Long-term ex-smokers vs never-smokers were less likely to have deficits in memory (OR, 0.79; 95% CI, 0.65 - 0.96; P < .05), vocabulary (OR, 0.73; 95% CI, 0.60 - 0.87; P < .05), phonemic fluency (OR, 0.73; 95% CI, 0.61 - 0.87; P < .05), and semantic fluency (OR, 0.75; 95% CI, 0.63 - 0.89; P < .05).
    • Recent ex-smokers vs never-smokers had less risk for deficits in vocabulary (OR, 0.65; 95% CI, 0.49 - 0.85; P < .05) and semantic fluency (OR, 0.72; 95% CI, 0.55 - 0.94; P < .05).
  • The only cognitive decline between phase 5 and phase 7 was for reasoning in current smokers (OR, 1.40; 95% CI, 1.11 - 1.75; P < .05) and recent ex-smokers (OR, 1.38; 95% CI, 1.07 - 1.77; P < .05) vs never-smokers.
  • Current smokers at phase 5 showed no dose-response association between pack-years of smoking and cognitive deficit or decline.
  • Post hoc analysis showed that recent ex-smokers had the smallest increase in alcohol use between phase 1 and phase 7 vs other groups and a greater increase in fruit and vegetable intake vs never-smokers.
  • Limitations of the study included specific subject population, self-reporting of smoking habits, written answers for testing verbal fluency, and only 2 time points to assess change.

Pearls for Practice

  • After adjustment for age, sex, sociodemographics, and health behaviors, middle-aged smokers vs never-smokers are more likely to have cognitive deficits in memory and decline in reasoning skills. Long-term ex-smokers vs never-smokers are less likely to have deficits in memory, vocabulary, and fluency.
  • Middle-aged adults who smoke have a higher risk for death or nonparticipation in cognitive tests.


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