0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Psychological Distress as a Risk Factor for Dementia Death FREE

Tom C. Russ, MRCPsych; Mark Hamer, PhD; Emmanuel Stamatakis, PhD; John M. Starr, FRCPEd; G. David Batty, PhD
[+] Author Affiliations

Author Affiliations: Scottish Dementia Clinical Research Network, NHS Scotland, Perth (Drs Russ and Starr); Alzheimer Scotland Dementia Research Centre (Drs Russ and Starr) and Centre for Cognitive Ageing & Cognitive Epidemiology (Drs Russ, Starr, and Batty), University of Edinburgh, Edinburgh, Scotland; Department of Epidemiology and Public Health, University College, London, England (Drs Hamer, Stamatakis, and Batty); and NHS Lothian, Edinburgh (Dr Starr).


Arch Intern Med. 2011;171(20):1859. doi:10.1001/archinternmed.2011.521.
Text Size: A A A
Published online

Current estimates suggest that neuropsychiatric disorders account for 28% of the global burden of disease.1 While depression and anxiety (commonly referred to as psychological distress) have been shown to be a consequence of dementia, the converse is less clear. The possibility that psychological distress might be a risk factor for dementia has major public health implications. However longitudinal studies—which are best placed to examine this relationship—have, with some exceptions,2,3 been small in scale (affecting study precision), excluded individuals younger than 65 years (limiting insights into the pre–older age origins of dementia), or have used clinical samples (reducing generalizability). Accordingly, we examined the role of psychological distress as a risk factor for and dementia death by pooling 10 large community-based cohort studies.

Participants were recruited from the Health Survey for England,4 an annual general population-based cross-sectional study (with a longitudinal component) representative of household-dwelling individuals in England. Results from 1994 through 2004 were pooled. Participants gave informed consent; ethical approval was obtained from the London Research Ethics Council.

Psychological distress was measured during a household visit using the 12-item General Health Questionnaire (GHQ-12), a widely used measure of psychological distress in population studies comprising items rating anxiety, depression, social dysfunction, and loss of confidence. Higher scores indicate greater distress. We used a cut off score of 4 or greater to denote psychological distress as validated against standardized psychiatric interviews.5 Dementia was identified from death certification and coded according to the International Classification of Diseases, Ninth Revision (ICD-9) codes 290.0 through 290.4 and 294.9 and International Statistical Classification of Diseases, 10th Revision (ICD-10) codes F01, F03, F09, and G30. Follow-up was until date of death or February 15, 2008, whichever came first.

We used Cox proportional hazards models to compute hazard ratios with accompanying 95% confidence intervals for GHQ-12 score in relation to dementia-related deaths. Study members scoring zero (no apparent distress) denoted the reference group. Models were adjusted for age, sex, occupational social class (OSC),6 parental OSC, age at leaving full-time education, current smoking (yes/no), alcohol consumption (units per week), and existing cardiovascular disease (CVD) (yes/no), and diabetes (yes/no). Statistical analyses were conducted using PASW statistics, version 18.0 (SPSS, Chicago, Illinois), and R for Max OS X, version R-2.13.0.

The initial sample included 85 261 adults (in 1996 the GHQ-12 was not used). After removing individuals who declined linkage to mortality records (n = 9325) and those with missing GHQ-12 data (n = 2865), the analytic sample comprised 73 071 individuals (54.8% women) with a mean (SD) age of 55.9 (14.3) years (range, 35-102 years). Data were missing for 1 or more variables in 21% (n = 15 355) of the sample. Individuals with missing data were more likely to be older, be female, belong to a manual OSC, leave school later, be a nonsmoker, drink alcohol moderately, and have CVD and diabetes.

Of the 10 170 deaths during follow-up, 455 had dementia coding. A higher GHQ-12 score was associated with increased risk of dementia death in an age-adjusted model (GHQ-12 score of 1-3: HR, 1.44 [95% CI, 1.17-1.78]; GHQ-12 score of 4-12: HR, 1.74 [95% CI, 1.36-2.22]; P value for trend, <.001). Adding all remaining covariates (sex, OSC, parental OSC, age at leaving full-time education, current smoking, alcohol consumption, and existing CVD and diabetes) led to some attenuation of effect but statistical significance at conventional levels was retained (GHQ-12 score of 1-3: HR, 1.27 [95% CI, 1.00-1.61]; GHQ-12 score of 4-12: HR, 1.56 [95% CI, 1.17-2.07]; P value for trend, .005). In the Figure we relate 7 categories of GHQ score to dementia death to provide more detailed insight into the shape of the relationship. There was evidence of a dose-response effect (P value for trend, .001). Excluding individuals with any missing data (sample n = 57 716; 361 dementia deaths) or dementia deaths within 5 years (sample n = 72 926; 310 dementia deaths)—the latter to explore reverse causality—did not affect our results.

Place holder to copy figure label and caption
Graphic Jump Location

Figure. Age- and sex-adjusted hazard ratios (HRs) with 95% confidence intervals for psychological distress in relation to the risk of dementia death: the Health Surveys for England. Reference = zero score on the 12-item General Health Questionnaire (GHQ-12). Higher score indicates greater distress.

We found an association between elevated psychological distress and an increased risk of dementia death in a large general population sample of apparently dementia-free adults, which remained after adjustment for age, sex, OSC, education, alcohol use, smoking, and existing CVD and diabetes. Cardiovascular risk factors have been linked with dementia,7 but the association found in our study remained after controlling for them, thus implicating other explanations for the gradient seen. One possibility is a toxic effect of hypercortisolemia in depression on the hippocampus.8 Further research is required to investigate whether appropriate treatment of depression reduces dementia risk.

Correspondence: Dr Russ, Alzheimer Scotland Dementia Research Centre, University of Edinburgh, 7 George Sq, Edinburgh EH8 9JZ, Scotland (tom.russ@nhs.net).

Author Contributions:Study concept and design: Russ, Hamer, and Batty. Acquisition of data: Hamer, Stamatakis, and Batty. Analysis and interpretation of data: Russ, Starr, and Batty. Drafting of the manuscript: Russ and Batty. Critical revision of the manuscript for important intellectual content: Russ, Hamer, and Stamatakis, Starr, and Batty. Statistical analysis: Russ and Batty. Obtained funding: Stamatakis and Batty. Study supervision: Hamer, Starr, and Batty.

Financial Disclosure: None reported.

Funding/Support: Dr Russ is supported by Alzheimer Scotland and he is employed in the NHS by the Scottish Dementia Clinical Research Network, which is funded by the Chief Scientist Office (part of the Scottish Government Health Directorates). Dr Russ and Starr are members of the Alzheimer Scotland Dementia Research Centre funded by Alzheimer Scotland. Drs Russ, Starr, and Batty are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). Funding from the BBSRC, EPSRC, ESRC, and MRC is gratefully acknowledged. GDB is a Wellcome Trust Fellow.

Prince M, Patel V, Saxena S,  et al.  No health without mental health.  Lancet. 2007;370(9590):859-877
PubMed   |  Link to Article
Kessing LV, Nilsson FM. Increased risk of developing dementia in patients with major affective disorders compared to patients with other medical illnesses.  J Affect Disord. 2003;73(3):261-269
PubMed   |  Link to Article
Lindsay J, Laurin D, Verreault R,  et al.  Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging.  Am J Epidemiol. 2002;156(5):445-453
PubMed   |  Link to Article
Colhoun H, Dong W, Prescott-Clarke P. Health Survey for England: Survey Methodology and Documentation. Vol 2. London, England: HMSO; 1994
Holi MM, Marttunen M, Aalberg V. Comparison of the GHQ-36, the GHQ-12 and the SCL-90 as psychiatric screening instruments in the Finnish population.  Nord J Psychiatry. 2003;57(3):233-238
PubMed   |  Link to Article
Employment Department Group/Office of Population Censuses and Surveys.  Standard Occupational Classification. London, England: HMSO; 1990
Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life.  Neurology. 2005;64(2):277-281
PubMed   |  Link to Article
Brown ES, Varghese FP, McEwen BS. Association of depression with medical illness: does cortisol play a role?  Biol Psychiatry. 2004;55(1):1-9
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure. Age- and sex-adjusted hazard ratios (HRs) with 95% confidence intervals for psychological distress in relation to the risk of dementia death: the Health Surveys for England. Reference = zero score on the 12-item General Health Questionnaire (GHQ-12). Higher score indicates greater distress.

Tables

References

Prince M, Patel V, Saxena S,  et al.  No health without mental health.  Lancet. 2007;370(9590):859-877
PubMed   |  Link to Article
Kessing LV, Nilsson FM. Increased risk of developing dementia in patients with major affective disorders compared to patients with other medical illnesses.  J Affect Disord. 2003;73(3):261-269
PubMed   |  Link to Article
Lindsay J, Laurin D, Verreault R,  et al.  Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging.  Am J Epidemiol. 2002;156(5):445-453
PubMed   |  Link to Article
Colhoun H, Dong W, Prescott-Clarke P. Health Survey for England: Survey Methodology and Documentation. Vol 2. London, England: HMSO; 1994
Holi MM, Marttunen M, Aalberg V. Comparison of the GHQ-36, the GHQ-12 and the SCL-90 as psychiatric screening instruments in the Finnish population.  Nord J Psychiatry. 2003;57(3):233-238
PubMed   |  Link to Article
Employment Department Group/Office of Population Censuses and Surveys.  Standard Occupational Classification. London, England: HMSO; 1990
Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life.  Neurology. 2005;64(2):277-281
PubMed   |  Link to Article
Brown ES, Varghese FP, McEwen BS. Association of depression with medical illness: does cortisol play a role?  Biol Psychiatry. 2004;55(1):1-9
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com

Users' Guides to the Medical Literature
Clinical Resolution

Users' Guides to the Medical Literature
Clinical Scenario