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Previous Volume 360:2302-2309 May 28, 2009 Number 22 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Purchase this article Editorial by Ewbank, D. C. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article by Weintraub, N. L. PubMed Citation

ABSTRACT

Background Research in Alzheimer's disease is focused mainly on younger old persons, whereas studies involving very old persons report attenuated relationships between the pathological features of Alzheimer's disease and dementia.

Methods We assessed 456 brains donated to the population-based Medical Research Council Cognitive Function and Ageing Study from persons 69 to 103 years of age at death. We used a standard neuropathological protocol that included measures of the pathological features of Alzheimer's disease, cerebral atrophy, and cerebrovascular disease. Neuropathological variables were dichotomized to represent no burden or a mild burden of pathological lesions as compared with a moderate or severe burden. Logistic regression was used to estimate the effect of age on the relationship between neuropathological features and dementia.

Results The difference in the prevalence of moderate and severe Alzheimer's-type pathological changes between persons with and those without dementia decreased with increasing age. The association between neocortical neuritic plaques and dementia was strong at 75 years of age (odds ratio, 8.63; 95% confidence interval [CI], 3.81 to 19.60) and reduced at 95 years of age (odds ratio, 2.48; 95% CI, 0.92 to 4.14), and similar attenuations with advancing age were observed in the association between other pathological changes related to Alzheimer's disease and dementia in all brain areas. In contrast, neocortical cerebral atrophy maintained a relationship with age in persons with dementia at both 75 years of age (odds ratio, 5.11; 95% CI, 1.94 to 13.46) and 95 years of age (odds ratio, 6.10; 95% CI, 2.80 to 13.28) and thus distinguished the cohort with dementia from the cohort without dementia.

Conclusions The association between the pathological features of Alzheimer's disease and dementia is stronger in younger old persons than in older old persons. Age must be taken into account when assessing the likely effect of interventions against dementia on the population.

Source Information

From the Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge (G.M.S., C.B.); the Academic Unit of Pathology, University of Sheffield, Sheffield (S.B.W., P.G.I., G.F.); and the Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge (F.E.M.) — all in the United Kingdom.

Drs. Savva and Wharton contributed equally to this article.

Address reprint requests to Dr. Wharton at the Academic Unit of Pathology, University of Sheffield, Medical School, Beech Hill Rd., Sheffield S10 2RX, United Kingdom, or at s.wharton{at}sheffield.ac.uk.

Full Text of this Article

Related Letters:

Age, Neuropathology, and Dementia
Chen L.-W.
Extract | Full Text | PDF  
N Engl J Med 2009; 361:1118, Sep 10, 2009. Correspondence

This article has been cited by other articles:

• Chen, L.-W. (2009). Age, Neuropathology, and Dementia. NEJM 361: 1118-1118 [Full Text]  
• (2009). All you need to read in the other general journals. BMJ 338: b2196-b2196 [Full Text]  
• Ewbank, D. C., Arnold, S. E. (2009). Cool with Plaques and Tangles. NEJM 360: 2357-2359 [Full Text]