BMJ  2004;329:881 (16 October), doi:10.1136/bmj.38216.604664.DE (published 2 September 2004)

Paper

Temporal relation between depression and cognitive impairment in old age: prospective population based study

¹ Section of Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, Netherlands, ² Department of Psychiatry, Leiden University Medical Centre, Netherlands

Abstract

Objective To examine the temporal relation between depression and cognitive impairment in old age.

Design Prospective, population based study with four years of follow up.

Setting City of Leiden, the Netherlands.

Participants 500 people aged 85 years at recruitment.

Main outcome measures Annual assessments of depressive symptoms (15 item geriatric depression scale), global cognitive function (mini-mental state examination), attention (Stroop test), processing speed (letter digit coding test), and immediate and delayed recall (12 word learning test).

Results At 85 years old, participants' depressive symptoms and cognitive impairment were highly significantly correlated (P < 0.001). During follow up, an accelerated annual increase of depressive symptoms was associated with impaired attention (0.08 points (95% confidence interval 0.01 to 0.16)), immediate recall (0.17 points (0.09 to 0.25)), and delayed recall (0.10 points (0.02 to 0.18)) at baseline. In contrast, depressive symptoms at baseline were not related to an accelerated cognitive decline during follow up (P > 0.05).

Conclusion Care givers should be aware of the development of depressive symptoms when cognitive impairment is present. However, the presence of depression only does not increase the risk of cognitive decline.

Introduction

Depression and cognitive impairment are among the most important mental health problems in elderly people. Both conditions have severe consequences, including diminished quality of life, functional decline, increased use of services, and high mortality.¹ Late onset depression and cognitive impairment often occur together, suggesting a close association between them.^2-4 It is not known, however, whether depression leads to cognitive decline or vice versa.^{4 5}

Clinical practice and research evidence suggest that depression precedes cognitive decline in old age.^5-10 However, inferring a relationship is hampered because most studies on this topic examined only the association between depression and the subsequent development of cognitive impairment.^6-14 As depression may be an early sign rather than an independent risk factor for cognitive impairment, the temporal relation between depression and cognitive impairment in old age remains unclear.

We followed up 500 elderly people living in the community with annual assessments of depressive symptoms and cognitive function in order to determine their temporal relation.

Participants and methods

Participants
The Leiden 85-plus study is a prospective, population based study of all 85 year old inhabitants of Leiden. Between 1 September 1997 and 1 September 1999, 599 participants were enrolled (response rate 87%). They were visited annually from the age of 85 to 89 years at their home for face to face interviews, and all gave their informed consent to participate.¹⁵ For the present analysis, we included the 500 participants (83%) without severe cognitive impairment at baseline (mini-mental state examination score 19 points).

Cognitive function
We assessed

• Global cognitive function with the mini-mental state examination¹⁶—scores range from 0 to 30 points, with lower scores indicating impaired cognitive functioning
  
• Attention with the third chart of the 40 item Stroop test—time needed to name the ink colour of incongruously printed names of colours, with higher scores indicating poorer attention
  
• Processing speed with the letter digit coding test—total number of correct digits assigned to letters according to a code key in 60 seconds, with lower scores indicating a slower speed
  
• Immediate and delayed recall with the 12 word learning test—12 pictures are presented to the participant, who is then asked to recall them. Outcome for immediate recall is the total number of words correctly recalled immediately after each procedure; outcome for delayed recall is the number correctly recalled after 20 minutes. Lower scores indicate impaired memory.
  

Depressive symptoms
We assessed depressive symptoms with the 15 item geriatric depression scale (GDS-15).¹⁷

Statistical analysis
We estimated the cross sectional correlation between depressive symptoms and cognitive function with Pearson's correlation coefficient. To assess the temporal relation between depression and cognitive function, we used separate linear mixed models adjusted for sex and level of education. We examined the impact of cognitive function at baseline on the course of depressive symptoms, restricting the analysis to participants without significant depressive symptoms at baseline (geriatric depression scale score 2 points). We examined the impact of depressive symptoms at baseline on the course of cognitive function, restricting the analysis to participants without serious cognitive impairment at baseline (mini-mental state exam score 24).

Results

During 1459 person-years of follow up (mean per person, 2.9 years), 39 people (8%) refused to participate in the repeated annual measurements, most of them at the first follow up visit. Of the 334 participants without significant depressive symptoms at baseline (geriatric depression scale score 2 points), 97 (29%) died and 28 (8%) declined to participate during follow up. Of the 415 non-demented participants at baseline (mini-mental state examination score 24 points), 124 (30%) died and 32 (8%) declined to participate during follow up.

Of the 500 participants, 184 (37%) were men, 303 (61%) had only a low level of education ( 6 years of schooling), 334 (67%) had no significant depressive symptoms (geriatric depression scale score 2 points), and 415 (83%) had no serious cognitive impairment (mini-mental state exam score 24 points).

At baseline, depressive symptoms were significantly correlated with lower scores for global cognitive function, attention, processing speed, and immediate and delayed recall and with higher test scores for attention (indicating reduced attention) (table 1).

View this table: [in this window] [in a new window]   Table 1 Cross sectional correlation of depressive symptoms* with various measures of cognitive function in 500 people aged 85 years living in the community

 

An accelerated annual increase of depressive symptoms during follow up was associated with impaired attention, poorer immediate recall, and poorer delayed recall at baseline (table 2). However, depressive symptoms at baseline were not associated with an accelerated cognitive decline during follow up (table 3).

View this table: [in this window] [in a new window]   Table 2 Impact of cognitive function at baseline on depressive symptoms from age 85 to 89 years in 334 people living in the community without depressive symptoms at baseline (GDS-15 score 2 points). Impact is additional annual increase of depressive symptoms score per SD of cognitive function test score at baseline (2.65 for global cognitive function, 31.59 for attention, 7.08 for processing, 5.72 for immediate recall, and 2.74 for delayed recall)

 

View this table: [in this window] [in a new window]   Table 3 Impact of depressive symptoms at baseline (GDS-15 score) on cognitive decline from age 85 to 89 years in 415 people living in the community without cognitive impairment at baseline (MMSE score 24 points). Impact is additional annual impact on cognitive function per SD of mean GDS-15 score at baseline (2.11)

 

Discussion

Depressive symptoms and cognitive impairment were highly significantly correlated cross sectionally, showing that they do co-occur in old age. Crucially, we found that cognitive impairment at baseline was associated with an accelerated increase of depressive symptoms, whereas depressive symptoms at baseline were not related to an accelerated cognitive decline. Thus our data show that cognitive impairment preceded the onset of depressive symptoms but not vice versa.

How does cognitive impairment lead to depression in old age?
We found specifically that impairment of attention and memory preceded the development of depressive symptoms. The awareness of cognitive decline may cause depression as a psychological reaction to the loss of cognitive functioning. Indeed, memory complaints in old age may be an early sign of dementia and, as such, upset elderly people.¹⁸ Thus, adequate functioning of attention and memory may be especially important to elderly people, explaining why their loss is associated with an accelerated increase of depressive symptoms. A common aetiology or sharing of risk factors is less likely to explain the association between depression and cognitive impairment. In that case, we would have expected that depressive symptoms precede cognitive decline also.

Comparison with other studies
Inferring causality in the relation between depression and cognitive impairment in old age has been hampered by the fact that most studies have examined only one direction of this relation. Some studies found that depression is a risk factor for the development of cognitive decline,^6-10 whereas others could not confirm this finding.^11-14 Examination of both directions of the relation between depression and cognitive impairment shows that depression in old age is a concomitant phenomenon of already existing cognitive impairment rather than an independent risk factor. Our findings, based on various measures of cognitive function instead of a dichotomous end point, are in line with those from a large population based study in people aged 65 and older showing that depression is an early manifestation rather than a predictor of Alzheimer's disease.¹⁹ Thus, in elderly people the presence of depressive symptoms does not mean that they are at increased risk of cognitive decline.

What is already known on this topic? Depression and cognitive impairment often occur together in old age The temporal relation between depression and cognitive impairment is unclear What this study adds? Impairment of attention or memory in old age precedes the development of depressive symptoms Presence of depressive symptoms, however, is not related to accelerated cognitive decline

Conclusions
We found that cognitive decline preceded depression in old age—specifically impairment of attention or memory preceded the development of depressive symptoms. Depression seems to be a concomitant symptom of cognitive impairment rather than an independent risk factor. Therefore, care givers should pay special attention to early detection and treatment of depressive symptoms in elderly people with cognitive impairment.

---

See also Clinical review p 895

This is the abridged version of an article that was posted on bmj.com on 2 September 2004: http://bmj.com/cgi/doi/10.1136/bmj.38216.604664.DE

Contributors: See bmj.com

Funding: This study was funded by unrestricted grants from the Netherlands Organisation of Scientific Research (ZonMw) and the Dutch Ministry of Health, Welfare, and Sports.

Competing interests: None declared.

Ethical approval: The medical ethics committee of Leiden University Medical Centre approved the study.

References

1. Macdonald AJD. Mental health in old age. BMJ 1997;315: 413-7.[Free Full Text]
2. Migliorelli R, Teson A, Sabe L, Petracchi M, Leiguarda R, Starkstein SE. Prevalence and correlates of dysthymia and major depression among patients with Alzheimer's disease. Am J Psychiatry 1995;152: 37-44.[Abstract/Free Full Text]
3. Zubenko GS, Zubenko WN, McPherson S, Spoor E, Marin DB, Farlow MR, et al. A collaborative study of the emergence and clinical features of the major depressive syndrome of Alzheimer's disease. Am J Psychiatry 2003;160: 857-66.[Abstract/Free Full Text]
4. Jorm AF. History of depression as a risk factor for dementia: an updated review. Aust N Z J Psychiatry 2001;35: 776-81.[CrossRef][ISI][Medline]
5. Schweitzer I, Tuckwell V, O'Brien J, Ames D. Is late onset depression a prodrome to dementia? Int J Geriatr Psychiatry 2002;17: 997-1005.[CrossRef][ISI][Medline]
6. Devanand DP, Sano M, Tang M-X, Taylor S, Gurland BJ, Wilder D, et al. Depressed mood and the incidence of Alzheimer's disease in the elderly living in the community. Arch Gen Psychiatry 1996;53: 175-82.[Abstract]
7. Yaffe K, Blackwell T, Gore R, Sands L, Reus V, Browner WS. Depressive symptoms and cognitive decline in nondemented elderly women. Arch Gen Psychiatry 1999;56: 425-30.[Abstract/Free Full Text]
8. Paterniti S, Verider-Taillerfer M-H, Dufouil C, Alpérovitch A. Depressive symptoms and cognitive decline in elderly people. Br J Psychiatry 2002;181: 406-10.[Abstract/Free Full Text]
9. Green RC, Cupples LA, Kurz A, Auerbach S, Go R, Sadovnick D, et al. Depression as a risk factor for Alzheimer disease. Arch Neurol 2003;60: 753-9.[Abstract/Free Full Text]
10. Wilson RS, Mendes de Leon CF, Bennett DA, Bienias JL, Evans DA. Depressive symptoms and cognitive decline in a community population of older persons. J Neurol Neurosurg Psychiatry 2004;75: 126-9.[Abstract/Free Full Text]
11. Dufouil C, Fuhrer R, Dartigues J-F, Alpérovitch A. Longitudinal analysis of the association between depressive symptomatology and cognitive deterioration. Am J Epidemiol 1996;144: 634-1.[Abstract/Free Full Text]
12. Henderson AS, Korten AE, Jacomb PA, Jorm AF, Rodgers B, Jacomb P, et al. The course of depression in the elderly: a longitudinal community-based study in Australia. Psychol Med 1997;27: 119-29.[CrossRef][ISI][Medline]
13. Cervilla JA, Prince M, Joels S, Mann A. Does depression predict cognitive outcome 9 to 12 years later? Evidence from a prospective study of elderly hypertensives. Psychol Med 2000;30: 1017-23.[CrossRef][ISI][Medline]
14. Broday H, Luscombe G, Anstey KJ, Cramsie J, Andrews G, Peisah C. Neuropsychological performance and dementia in depressed patients after 25-year follow-up: a controlled study. Psychol Med 2003;33: 1263-75.[CrossRef][ISI][Medline]
15. Bootsma-van der Wiel A, van Exel E, de Craen AJM, Gusskloo J, Lagaay AM, Knook DL, et al. A high response is not essential to prevent selection bias: results from the Leiden 85-plus study. J Clin Epidemiol 2002;55: 1119-25.[CrossRef][ISI][Medline]
16. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12: 189-98.[CrossRef][ISI][Medline]
17. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982;1: 37-49.
18. Jonker C, Geerlings MI, Schmand B. Are memory complaints predictive for dementia? A review of clinical and population-based studies. Int J Geriatr Psychiatry 2000;15: 983-91.[CrossRef][ISI][Medline]
19. Chen P, Ganguli M, Mulsant BH, DeKosky ST. The temporal relationship between depressive symptoms and dementia. Arch Gen Psychiatry 1999;56: 261-6.[Abstract/Free Full Text]

(Accepted 19 July 2004)

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Articles

Depression accompanies cognitive decline
BMJ 2004 329: 0. [Full Text] [PDF]

Recent developments: Suicide in older people

Henry O'Connell, Ai-Vyrn Chin, Conal Cunningham, and Brian A Lawlor
BMJ 2004 329: 895-899. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Dotson, V. M., Resnick, S. M., Zonderman, A. B. (2008). Differential Association of Concurrent, Baseline, and Average Depressive Symptoms With Cognitive Decline in Older Adults. AJGP 16: 318-330 [Abstract] [Full text]  
• Wilson, R. S., Arnold, S. E., Beck, T. L., Bienias, J. L., Bennett, D. A. (2008). Change in Depressive Symptoms During the Prodromal Phase of Alzheimer Disease. Arch Gen Psychiatry 65: 439-445 [Abstract] [Full text]  
• Erlangsen, A., Zarit, S. H., Conwell, Y. (2008). Hospital-Diagnosed Dementia and Suicide: A Longitudinal Study Using Prospective, Nationwide Register Data. AJGP 16: 220-228 [Abstract] [Full text]  
• VINKERS, D., van der MAST, R. (2008). Depression and Executive Dysfunction in Old Age. Am. J. Psychiatry 165: 136-136 [Full text]  
• LYNESS, J. M., CUI, X., TU, X., KING, D. A., CAINE, E. D. (2008). Dr. Lyness and Colleagues Reply. Am. J. Psychiatry 165: 136-137 [Full text]  
• Raji, M. A., Reyes-Ortiz, C. A., Kuo, Y.-F., Markides, K. S., Ottenbacher, K. J. (2007). Depressive Symptoms and Cognitive Change in Older Mexican Americans. J Geriatr Psychiatry Neurol 20: 145-152 [Abstract]  
• Vanlaere, L., Bouckaert, F., Gastmans, C. (2007). Care for suicidal older people: current clinical-ethical considerations. J. Med. Ethics 33: 376-381 [Abstract] [Full text]  
• Maraldi, C., Volpato, S., Penninx, B. W., Yaffe, K., Simonsick, E. M., Strotmeyer, E. S., Cesari, M., Kritchevsky, S. B., Perry, S., Ayonayon, H. N., Pahor, M. (2007). Diabetes Mellitus, Glycemic Control, and Incident Depressive Symptoms Among 70- to 79-Year-Old Persons: The Health, Aging, and Body Composition Study. Arch Intern Med 167: 1137-1144 [Abstract] [Full text]  
• Langfitt, J. T., Westerveld, M., Hamberger, M. J., Walczak, T. S., Cicchetti, D. V., Berg, A. T., Vickrey, B. G., Barr, W. B., Sperling, M. R., Masur, D., Spencer, S. S. (2007). Worsening of quality of life after epilepsy surgery: Effect of seizures and memory decline. Neurology 68: 1988-1994 [Abstract] [Full text]  
• Raskin, J., Wiltse, C. G., Siegal, A., Sheikh, J., Xu, J., Dinkel, J. J., Rotz, B. T., Mohs, R. C. (2007). Efficacy of Duloxetine on Cognition, Depression, and Pain in Elderly Patients With Major Depressive Disorder: An 8-Week, Double-Blind, Placebo-Controlled Trial. Am. J. Psychiatry 164: 900-909 [Abstract] [Full text]  
• Lang, I., Wallace, R. B., Huppert, F. A., Melzer, D. (2007). Moderate alcohol consumption in older adults is associated with better cognition and well-being than abstinence. Age Ageing 36: 256-261 [Abstract] [Full text]  
• Han, L., McCusker, J., Abrahamowicz, M., Cole, M., Capek, R. (2006). The Temporal Relationship Between Depression Symptoms and Cognitive Functioning in Older Medical Patients--Prospective or Concurrent?. J. Gerontol. A Biol. Sci. Med. Sci. 61: 1319-1323 [Abstract] [Full text]  
• Ganguli, M., Du, Y., Dodge, H. H., Ratcliff, G. G., Chang, C.-C. H. (2006). Depressive Symptoms and Cognitive Decline in Late Life: A Prospective Epidemiological Study. Arch Gen Psychiatry 63: 153-160 [Abstract] [Full text]  
• STEK, M. L., VINKERS, D. J., GUSSEKLOO, J., VAN DER MAST, R. C., BEEKMAN, A. T. F., WESTENDORP, R. G. J. (2006). Natural history of depression in the oldest old: Population-based prospective study. Br. J. Psychiatry 188: 65-69 [Abstract] [Full text]  
• De Ronchi, D., Bellini, F., Berardi, D., Serretti, A., Ferrari, B., Dalmonte, E. (2005). Cognitive Status, Depressive Symptoms, and Health Status as Predictors of Functional Disability Among Elderly Persons With Low-to-Moderate Education: The Faenza Community Aging Study. AJGP 13: 672-685 [Abstract] [Full text]  
• Vinkers, D. J., Stek, M. L., van der Mast, R. C., de Craen, A.J.M., Le Cessie, S., Jolles, J., Westendorp, R. G.J., Gussekloo, J. (2005). Generalized atherosclerosis, cognitive decline, and depressive symptoms in old age. Neurology 65: 107-112 [Abstract] [Full text]  
• (2005). Temporal Relation Between Depression and Cognitive Impairment in Elderly. JWatch Neurology 2005: 1-1 [Full text]  
• (2004). Cognitive Impairment Generally Precedes Depression in Old Age. JWatch Psychiatry 2004: 9-9 [Full text]  
• (2004). Cognitive Impairment Generally Precedes Depression in Old Age. JWatch General 2004: 3-3 [Full text]  

Rapid Responses:

Read all Rapid Responses

Other intracranial causes of cognitive impairment should be asertained

Dr Abdulfatai Kunle Salawu MBBS,FMCP(Nig), et al.
bmj.com, 8 Sep 2004 [Full text]

This could be loss of DHEA of old age...

James M. Howard
bmj.com, 15 Oct 2004 [Full text]

Depression in Dementia

Ramneesh Puri
bmj.com, 15 Oct 2004 [Full text]

Depression and cognitive impairment: multiple implications!

Dr. Naseem A. Qureshi MD, IMAPA, LMIPS
bmj.com, 17 Oct 2004 [Full text]

Depression accompanying cognitive decline

Dietmar Fuchs, et al.
bmj.com, 29 Oct 2004 [Full text]