Dementia: A general introduction

Prevalence of dementia

Dementia is estimated1 to afflict over 35.5 million people worldwide -- this includes nearly 10 million people in Europe, nearly 4.4 million in North America, nearly 7 million in South and Southeast Asia, about 5.5 million in China and East Asia and about 3 million in Latin America.

The estimated prevalence for over 60s is 4.7% worldwide. Because this is a disorder of age, prevalence is of course greatly affected by the proportion of people reaching their senior years. Hence the prevalence is higher in the more developed countries: the estimated prevalence in Western Europe and North America is 7.2% and 6.9% respectively, compared to 2.6% in Africa.

What kinds of dementia are most common?

The prevalence of the various dementia types is a complicated story. Certainly Alzheimer's disease is by far the most common type of dementia, accounting for perhaps 70% of all dementias (although a 2006 study13 suggested that non-Alzheimer dementias were as common as Alzheimer's — however this was based on dementia among military veterans). The second most common dementia is almost certainly vascular dementia, which may account for some 17% of dementias. However, the actual numbers are made uncertain by the fact that these two dementias often occur together.

At minimum, around a quarter of Alzheimer's cases have been found, on autopsy, to also have vascular pathology; this proportion reaches higher levels when the samples are not restricted to dementia clinics. One such community-based study2, for example, found 45% of the Alzheimer's cases also showed significant vascular pathology. Another, U.K., study3 found a similar proportion (46%).

Another, large long-running, study14 has found that only 30% of people with signs of dementia had Alzheimer’s disease alone. 42% had Alzheimer’s disease with cerebral infarcts (strokes) and 16% had Alzheimer’s disease with Parkinson’s disease (including two people with all three conditions). Infarcts alone caused another 12% of the cases. Vascular dementia caused another 12%.

Although there are other types of dementia that also co-occur with Alzheimer's, mixed dementia generally refers to the co-occurrence of Alzheimer's and vascular dementia.

The other important dementia type that co-occurs with Alzheimer's at a high rate is dementia with Lewy bodies, also considered to be one of the most common dementias (although, due to inconsistent criteria, estimates of its actual prevalence vary wildly). It is estimated to co-occur with Alzheimer's pathology around half the time. At a lesser frequency, but still high, is Parkinson's disease dementia — about 20% of Alzheimer's patients also have Parkinson's disease.

But it is probably fair to say that the distinction between these dementia types is not clear-cut. Lewy bodies are found in a high proportion of both Alzheimer's and Parkinson's patients — the number of cases of 'pure' Lewy body dementia is much smaller. It's been said, in fact, that the main difference between Lewy body dementia and Parkinson's disease dementia lies in the timing — Parkinson's disease dementia will be preceded by at least a year and more likely a number of years, by full-blown Parkinson's disease.

Regardless of the difficulties in establishing clear clinical criteria, however, there is no doubt that Alzheimer's co-occurs with vascular pathology or Lewy body pathology at a startlingly high rate.

One of the problems with clearly distinguishing between these types of dementia is a happy one: vascular and Alzheimer's pathology can be found, at autopsy, in many elderly brains that have not shown symptoms of dementia.

For example, in one community-based study4, in which the median age at death was around 85 for the 209 individuals, 48% had had dementia, of whom 64% showed Alzheimer's pathology. However, 33% of those who had not had dementia showed similar levels of Alzheimer's plaques. Similarly, some amount of tau tangles (another aspect of Alzheimer's pathology) was found in 61% of the demented and 34% of the non-demented individuals. Finally, multiple vascular pathology was found in 46% of the demented group and 33% of the non-demented, and vascular lesions were equally common in both.

And in the large long-running study mentioned earlier14, in those without dementia, brain autopsy revealed the presence of Alzheimer’s in 24% of cases, and infarctions in 18%.

How likely am I to develop dementia?

The question of how likely any person is to develop dementia must begin with estimates of prevalence, but this of course is only the very beginning of the story.

Estimating prevalence is complicated by the fact that dementia is greatly affected by lifestyle, environmental, and genetic factors, and consequently prevalence varies a lot depending on geographic region.

Different dementia sub-types have different causes, and some give a much greater weight to genetic or environmental factors than others. However, the finding that dementia risk is much greater in those with more than one pathology, and that Alzheimer’s pathology with cerebral infarcts is a very common combination, adds to growing evidence that dementia risk might be reduced with the same tools we use for cardiovascular disease such as control of blood cholesterol levels and hypertension.

Age as a factor

The first American study to use nationally representative data5 (rather than extrapolating from regional data) came up with a figure of 13.9% of those aged 71 and older (one in seven). But age of course makes all the difference in the world. The study found 5% of those aged 71 to 79, rising to 37.4% of those age 90 and older.

Although all the dementia types show an increase with age, Alzheimer's is particularly a disorder of age: although the study found only 46.7% of those with dementia in their 70s had Alzheimer's, for those in their 90s, Alzheimer's was the dementia type for 79.5% of them.

An Italian study of over 2000 seniors over 80 years old6 confirms that dementia does indeed keep increasing with age (it had been thought that risk leveled off for those who reached their 90s). The study found that 13.5% of those aged 80 to 84 had dementia, rising sharply to 30.8% of those 85 to 89, 39.5% of those 90 to 94, and 52.8% among those older than 94.

Gender as a factor

A number of studies have found differences between men and women, or between difference ethnicities, but this large, nationally representative study found that, although on the face of it there were race and gender differences, these differences disappeared once age, years of education, and presence of at least one "Alzheimer's gene" was taken into account.

However, an American study of over 900 seniors over 90 years old7 found that women of this age were much more likely to have dementia than men (some 45% of them, compared to 28% of the men), and that the likelihood of having dementia kept increasing with age for the women, but not for the men. Of course, more women than men survive to this age (some two-thirds of the participants were women).

Interestingly, education was protective for the women (the risk of dementia decreasing the more years of education the individual had had) but not for the men. The study participants were not, however, a random sampling -- they all came from the same retirement community, and most were white and of high socioeconomic status. Given that, and considering the times in which they were born, it seems likely that there would be far more variability in educational level among the women than the men. The men, while less likely to develop dementia, did tend to decline faster if they did develop it.

The Italian oldest-old study, too, found more women than men had dementia: across all ages, 25.8% of the women and 17.1% of the men.

These figures don't of course tell us how many develop dementia at those ages. Obviously, survival rates are a factor, and as we saw in the other study, male and female survival rates do vary. The figures for new cases of dementia developing in these age bands were:

  • 6% at 80 to 84 years;
  • 12.4% at 85 to 89 years;
  • 13.1% from 90 to 94 years; and
  • 20.7% among those over 94.

These figures make even more clear what was apparent in the earlier figures: dementia jumps suddenly in the later half of the 80s, and again in the later half of the 90s.

Importantly, however, the incidence of new cases shows us how important the gender difference in survival rates is: the difference in prevalence is much smaller in these terms --9.2% among women and 7.2% among men.

The study, which canvassed everyone in the age group within a specific geographical area and had an 88% response rate, had a ratio of 74 women to 26 men. Because the number of men at the very highest ages was so small, we can't draw any firm conclusions about gender differences at those ages.

The Italian study involves a very different population from that of the American study: Varese is in a heavily industrialised part of northern Italy, with a high immigrant population, and the average amount of education was only 5.1 years.

A review of 26 studies looking at dementia prevalence in Europe8 confirmed rates for men rising from 1.8% in the 65-69 years age range up to 30% in the over 90 years age group, and for women rising from 1.5% to 30% in the 80-85 years age band. However (and confirming the American study), rates in the oldest old for women rose to over 50% in those over 95 years.

Early onset of dementia

The average age at the onset of dementia is around 80 years. Early-onset dementia is defined arbitrarily (and variably) as occurring before 60-65. Early-onset cases have been estimated to make up about 6-7% of all cases of Alzheimer's disease, and though a lot of attention has been given to them, only about 7% of early-onset cases are in fact familial9.

Familial cases involve mutations in specific genes (the APP or presenilin genes); they do not include what is popularly referred to as the "Alzheimer's gene" — variants of APOE. A 1995 study10 calculated that a person with no family history of Alzheimer's disease who has an e4 allele has a lifetime risk of 29%, compared to a risk of 9% if they don't have an e4 allele. In other words, if you don't have any of the Alzheimer's risk genes, or any family history, you only have a 9% risk of developing Alzheimer's, and even if you do have the "Alzheimer's gene", your chance of not getting Alzheimer's is still over 70%. Your risk does, however, go up dramatically if both your APOE alleles are e4.

A large study11 found, however, that there were both ethnic and gender differences for the risk of this genetic factor. The effect of having an e4 allele was much greater among Japanese compared to Caucasian, and greater for Caucasian compared to African American and Hispanic. Additionally, the effect of having an e4 allele becomes less significant after 70.

There is evidence12 that the age of onset for both Alzheimer's and Parkinson's diseases, for those genetically disposed, is controlled by genes on chromosome 10.

References: 
  1. From the 2009 World Alzheimer's Report: http://www.alz.co.uk/research/worldreport/
  2. Lim A, Tsuang D, Kukull W, et al. 1999. Cliniconeuropathological correlation of Alzheimer’s disease in a community-based case series. Journal of the American Geriatric Society, 47, 564-569.
  3. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). 2001. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet, 357, 169-175.
  4. Langa, K.M., Foster, N.L. & Larson, E.B. 2004. Mixed Dementia: Emerging Concepts and Therapeutic Implications. JAMA, 292(23), 2901-2908.
  5. Plassman, B.L. et al. 2007. Prevalence of Dementia in the United States: The Aging, Demographics, and Memory Study. Neuroepidemiology, 29, 125-132. 
  6. Lucca, U. et al. 2009. Risk of dementia continues to rise in the oldest old: The Monzino 80-plus Study. Presented on July 14, 2009, at the annual International Conference on Alzheimer's Disease in Vienna. http://www.alz.org/icad/documents/abstracts/abstracts_prev_ICAD09.pdf
  7. Corrada, M.M. et al. 2008. Prevalence of dementia after age 90: Results from The 90+ Study. Neurology, 71 (5), 337-343.
  8. Reynish, E. et al. 2009. Systematic Review and Collaborative Analysis of the Prevalence of Dementia in Europe. Presented on July 14, 2009, at the annual International Conference on Alzheimer's Disease in Vienna. http://www.alz.org/icad/documents/abstracts/abstracts_prev_ICAD09.pdf
  9. Nussbaum, R.L. & Ellis, C.E. 2003. Alzheimer's Disease and Parkinson's Disease. New England Journal of Medicine, 348 (14), 1356-1364. http://content.nejm.org/cgi/content/full/348/14/1356#R23
  10. Seshadri S, Drachman DA, Lippa CF. 1995. Apolipoprotein E epsilon 4 allele and the lifetime risk of Alzheimer's disease: what physicians know, and what they should know. Archives of Neurology, 52, 1074-1079. http://tinyurl.com/ya7vss7 
  11. Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. JAMA 1997;278:1349-1356. http://tinyurl.com/yb9tdju
  12. Li, Y. et al. 2002. Age at Onset in Two Common Neurodegenerative Diseases Is Genetically Controlled. American Journal of Human Genetics, 70, 985-993. Press release
  13. Ross, E.D. et al. 2006. Changing Relative Prevalence of Alzheimer Disease versus Non-Alzheimer Disease Dementias: Have We Underestimated the Looming Dementia Epidemic? Dementia and Geriatric Cognitive Disorders, 22 (4), 273-277.
  14. Schneider, J.A., Arvanitakis, Z., Bang, W. & Bennett, D.A. 2007. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology, published ahead of print June 13.

 

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