Int J Geriatr Psychiatry. 2016 Jun;31(6):601-10. doi: 10.1002/gps.4366.
The role of cognitive reserve on terminal decline: a cross-cohort analysis from two European studies: OCTO-Twin, Sweden, and Newcastle 85+, UK.
Cadar D1, Stephan BC2, Jagger C2, Johansson B3, Hofer SM4, Piccinin AM4, Muniz-Terrera G1
1MRC Unit for Lifelong Health and Ageing at University College London, London, UK.
2Institute of Health and Society, Newcastle University, Newcastle, UK.
3Department of Psychology, University of Gothenburg, Gothenburg, Sweden.
4Department of Psychology, University of Victoria, Victoria, Canada.
Cognitive performance shows a marked deterioration in close proximity to death, as postulated by the terminal decline hypothesis. The effect of education on the rate of terminal decline in the oldest people (i.e. persons 85+ years) has been controversial and not entirely understood. In the current study, we investigated the rate of decline prior to death with a special focus on the role of education and socioeconomic position, in two European longitudinal studies of ageing: the Origins of Variance in the Old‐Old: Octogenarian Twins (OCTO‐Twin) and the Newcastle 85+ study.
A process‐based approach was used in which individuals’ cognitive scores were aligned according to distance to death. In a coordinated analysis, multilevel models were employed to examine associations between different markers of cognitive reserve (education and socioeconomic position) and terminal decline using the mini‐mental state examination (MMSE), controlling for age at baseline, sex, dementia incidence and time to death from the study entry to the time of death within each cohort.
The current findings suggest that education was positively associated with higher MMSE scores prior to death in the OCTO‐Twin, but not in the Newcastle 85+ study, independent of socioeconomic position and other factors such as baseline age, sex and time to death from the study entry. However, education was not associated with the rate of terminal decline in both of these studies.
Our results offer only partial support to the cognitive reserve hypothesis and cognitive performance prior to death.
© 2015 The Authors International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.
MMSE; cognition; cognitive reserve; death; dementia; education; longitudinal study; mixed multilevel; terminal decline
In this paper, we are interested in the role of education as a marker of cognitive reserve in determining terminal decline. A considerable body of evidence suggests that cognitive performance shows a marked deterioration in the proximity of death, a phenomenon known as “terminal decline”. The concept of “terminal decline” was first coined by Kleemeier in 1962, emphasising a within-person process of change or transition from a preterminal phase of relative stability into a terminal phase of rapid decline that ends with death . However, this theoretical conceptualisation lacks time specificity. Previous work by Birren and Cunningham (1985) suggested that “cognitive and social slipping” may occur some “months to years” before death without providing an exact period of when this transition occurs .
New published reports in the specialised field, refer to a variation in findings, ranging from 7-8 years to 6-7 months acceleration before death according to various cognitive outcomes [3-11].
This disparity could be driven by one or more specific biological conditions determining the disease processes, including dementia, cardiovascular conditions, diabetes or organ failures [12-14].
A plausible explanation is that, in the absence of neuropathogenic cognitive decline, most people may maintain stable or slightly declining functions into old age, with a more severe deterioration indicating biological compromise (e.g., cardiovascular disease). Periods characterised by slow-but-steady cognitive decline may be linked to other protracted preterminal causes of death (e.g., neoplasms, vascular diseases such as stroke and heart attack) known to weaken cognitive performance and exacerbate cognitive decline. These are more likely reflecting the relatively acute nature of vascular causes of death corresponding to abrupt influences on cognition, which is associated with premature mortality. Furthermore, these models are based on restrictive assumptions that everyone experiences a similar point of terminal decline in time, and only limited work has explored this variation otherwise. In addition, most findings are usually coming from studies with wider age range and more focus research needs to target specifically the oldest old category.
All in all, these results refer to a variation in cognitive changes before death, partially due to interindividual differences and due to the diversity of methodology employed which makes difficult to define the period of terminal decline as a holistic phenomenon 
One of the modifiable risk factors, which have received a substantial interest in this area of research, is education. Often used as a proxy for cognitive reserve, education has been shown to be protective against faster rates of cognitive decline in healthy individuals  and a delayed onset of dementia. Cognitive reserve hypothesis refers to the ability to make flexible and efficient use of available brain reserve when performing various cognitive ability tasks [16-20].
In this context, Richards and Deary proposed a life course approach to cognitive reserve (Figure 1 below) , in which they showed how major influencing factors such as education, occupation and socioeconomic environment are influencing neural networks and premorbid cognitive ability or perhaps mediate the clinical expression of cognitive impairment as a response to the CNS lesions (e.g., white matter lesions, brain atrophy, plaques, tangles, vascular damage or metabolic or endocrine diseases injury).
Figure 1. A life course model of cognitive reserve adapted from Richards & Deary (2005) 
The less understood part of these conceptual models is that brain reserve is thought to constitute the only meaningful difference between individuals (Figure 2), with the idea that accumulated damage either does or does not reach the threshold necessary for functional deficits, especially when related to the rate of decline.
Figure 2. A conceptual diagnram of brain and cognitive reserve taken from Pinto & Tandel (2016) 
Many reports are indicating an association between education and level of cognitive performance, but not with the speed of the change immediately prior to death [7, 23, 24].
In contrast, other reports are showing that education appears to delay the onset of terminal decline in the oldest old  and to impact the rate of terminal decline differently according to various domains .
In this study, we examined terminal decline in measures of global function the role of education on these trajectories, in a coordinated approach analysis across two European longitudinal studies of older people.
Our results revealed an accelerated change in one of the two cohorts investigated (in the Swedish cohort-OCTO), after accounting for individual differences such as sex, age at baseline and time to death from the study entry. Some differences were depicted in this cross-cohort comparison. First, the lag period which examined terminal decline was slightly different between these two studies, with one study having a longer study period available to describe the accelerated rate of change in the Swedish cohort, in contrast to a relevant shorter period of follow-up in the British study. Second, the ceiling effects observed with the MMSE arise when performance is favourably overstated by personal characteristics such as high education, independent of prior cognitive ability, and therefore reducing its sensitivity. However, MMSE has been endorsed to a great reliance in the verbal items , so consequently, decline in the MMSE could represent a sensitivity threshold for the verbal task component in the presence of neurodegeneration.
Lastly, our results showed that education did not moderate the rate of cognitive decline prior to death in both of these observational studies investigated (Figure 3), despite that education was found to modify the association between AD pathology assessed post-mortem and levels of cognitive function in proximity to death in some other studies .
Figure 3 Model estimated mean curves for incident dementia and non-cases for different values of education with the additional upper and lower bands of 3 years education.
The significant finding of our work was that education influences the level of performance, even at the time of death.
- Kleemeier, R.W., Intellectual changes in the senium. 1962: Proceedings of the American Statistical Association.
- Birren, J.E. and W. Cunningham, Research on the psychology of aging: Principles, concepts, and theory, in Handbook of the psychology of aging, J.E. Birren and K.W. Schaie, Editors. 1985, Van Nostrand Reinhold: New York. p. 3-34.
- Wilson, R.S., et al., Terminal dedifferentiation of cognitive abilities. Neurology, 2012. 78(15): p. 1116-1122.
- Wilson, R.S., et al., Terminal decline in cognitive function. Neurology, 2003. 60(11): p. 1782-1787.
- Wilson, R.S., et al., Terminal cognitive decline: accelerated loss of cognition in the last years of life. Psychosom. Med, 2007. 69(2): p. 131-137.
- Thorvaldsson, V., et al., Onset of terminal decline in cognitive abilities in individuals without dementia. Neurology, 2008. 71(12): p. 882-887.
- Piccinin, A.M., et al., Terminal decline from within- and between-person perspectives, accounting for incident dementia. J. Gerontol. B Psychol. Sci. Soc. Sci, 2011. 66(4): p. 391-401.
- Palmore, E. and W. Cleveland, Aging, terminal decline, and terminal drop. J Gerontol, 1976. 31(1): p. 76-81.
- Muniz-Terrera, G., et al., Investigating terminal decline: results from a UK population-based study of aging. Psychol. Aging, 2013. 28(2): p. 377-385.
- Muniz-Terrera, G., et al., Are terminal decline and its potential indicators detectable in population studies of the oldest old? Int. J Geriatr. Psychiatry, 2011. 26(6): p. 584-592.
- Gerstorf, D. and N. Ram, Inquiry into terminal decline: five objectives for future study. Gerontologist, 2013. 53(5): p. 727-737.
- Anstey, K.J., H.A. Mack, and C. von Sanden, The relationship between cognition and mortality in patients with stroke, coronary heart disease, or cancer. European Psychologist, 2006. 11(3): p. 182-195.
- Backman, L. and S.W.S. MacDonald, Death and cognition: Synthesis and outlook. European Psychologist, 2006. 11: p. 224-235.
- Hassing, L.B., et al., Diabetes mellitus is a risk factor for vascular dementia, but not for Alzheimer’s disease: a population-based study of the oldest old. Int. Psychogeriatr, 2002. 14(3): p. 239-248.
- Richards, M. and A. Sacker, Lifetime antecedents of cognitive reserve. J Clin Exp. Neuropsychol, 2003. 25(5): p. 614-624.
- Stern, Y., Cognitive reserve. Neuropsychologia, 2009. 47(10): p. 2015-2028.
- Stern, Y., What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol. Soc, 2002. 8(3): p. 448-460.
- Stern, Y., Cognitive reserve: A catalyst for research. Journal of the Neurological Sciences, 2009. 283(1-2): p. 256-256.
- Stern, Y., Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol, 2012. 11(11): p. 1006-1012.
- Stern, Y., et al., Rate of memory decline in AD is related to education and occupation: cognitive reserve? Neurology, 1999. 53(9): p. 1942-1947.
- Richards, M. and I.J. Deary, A life course approach to cognitive reserve: A model for cognitive aging and development? Annals of Neurology, 2005. 58(4): p. 617-622.
- Pinto, C. and K. Tandel, Cognitive reserve: Concept, determinants, and promotion. Journal of Geriatric Mental Health, 2016. 3(1): p. 44-51.
- Laukka, E.J., S.W. MacDonald, and L. Backman, Contrasting cognitive trajectories of impending death and preclinical dementia in the very old. Neurology, 2006. 66(6): p. 833-838.
- Johansson, B., et al., Change in cognitive capabilities in the oldest old: the effects of proximity to death in genetically related individuals over a 6-year period. Psychol. Aging, 2004. 19(1): p. 145-156.
- Muniz-Terrera, G., et al., Education associated with a delayed onset of terminal decline. Age Ageing, 2014. 43(1): p. 26-31.
- Batterham, P.J., A.J. Mackinnon, and H. Christensen, The effect of education on the onset and rate of terminal decline. Psychol. Aging, 2011. 26(2): p. 339-350.
- Xu, G., et al., Screening for mild cognitive impairment (MCI) utilizing combined mini-mental-cognitive capacity examinations for identifying dementia prodromes. Int. J. Geriatr. Psychiatry, 2002. 17(11): p. 1027-1033.
- Bennett, D.A., et al., Apolipoprotein E epsilon4 allele, AD pathology, and the clinical expression of Alzheimer’s disease. Neurology, 2003. 60(2): p. 246-252.
This work was supported by the Alzheimer’s Society [Grant number 144] and by the Medical Research Council [MRC Unit for Lifelong Health and Ageing at UCL Programme Number MC_UU_12019/1]. The coauthors were funded by the Swedish Research Council for Health, Working Life and Welfare; US National Institutes of Health/National Institute of Aging [P01AG043362] and AXA Research Fund.
Research reported in this publication was also supported by the US National Institute on Aging of the National Institutes of Health under award number P01AG043362 for the Integrative Analysis of Longitudinal Studies of Aging research network. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Dorina Cadar Ph.D.
Research Associate in Dementia
University College London
Department of Epidemiology and Public Health
3rd Floor, Room 355a
1-19 Torrington Place
London, WC1E 6BT