Cholesterol and Alzheimer type dementia among adults with Down syndrome
Frank Buckley
A summary of research by Warren Zigman and colleagues investigating the link between cholesterol levels and Alzheimer type dementia among adults with Down syndrome.
Buckley F. Cholesterol and Alzheimer type dementia among adults with Down syndrome. Down Syndrome Research and Practice. 2008;12(2);91-91.
doi:10.3104/research-highlights.2052
It is clear that there is an increased incidence of early onset dementia of
the Alzheimer type among people with Down syndrome. Estimates vary, perhaps due
to different diagnostic criteria and population biases, but around 10% of people
with Down syndrome may be diagnosed with Alzheimer type dementia between the
ages of 40 and 49, rising to around 30% between the ages of 50 and 59.
Little is known about factors that influence the development of dementia of the
Alzheimer type among people with Down syndrome. Increasing age, the presence of
the ε4 allele of the apolipoprotein E (APOE) gene, and age at menopause have
been shown to increase the risk. It has been suggested that greater mental
activity and stimulation may delay the onset of dementia and that therefore
improved community living and social inclusion may reduce the prevalence of
dementia among people with Down syndrome, but this is yet to be clearly
demonstrated.
The primary neuropathological features of Alzheimer's disease include protein
deposits called β-amyloid plaques and neurofibrillary tangles. Cholesterol may
be involved in the formation, deposition and removal of β-amyloid. It has been
suggested that cholesterol levels may be a risk factor for Alzheimer's disease
in the general population. If this is the case, then high cholesterol levels may
be a risk factor for adults with Down syndrome. Conversely, the use of
cholesterol-lowering drugs may delay the onset or reduce the incidence of
dementia of the Alzheimer type among people with Down syndrome. Statins are
widely prescribed to lower cholesterol.
Warren Zigman and colleagues followed 123 adults with Down syndrome between May
1998 and April 2006. The participants were aged between 41 and 78 years at the
start of the study and did not have dementia. The participants' were assessed
regularly for behaviour changes indicative of dementia and medical records were
reviewed. APOE genotypes were determined from blood samples. Cholesterol levels
were determined from medical records of tests prior to the start of the study.
The study found that participants with high cholesterol levels were more than
twice as likely to develop dementia of the Alzheimer type during the course of
the study. The study also found that participants with high cholesterol levels
who used statins had a 40% lower chance of developing Alzheimer type dementia
during the course of the study. The risk for participants with lower cholesterol
levels was not influenced by statin use.
This paper suggests that cholesterol is an important risk factor for Alzheimer's
disease among people with Down syndrome and that perhaps cholesterol-lowering
drugs could delay or prevent the onset of Alzheimer type dementia. However, the
authors note that clinical trials of statins among the general population have
not been encouraging and emphasise the need for rigorous clinical trials to
establish a protective effect (if any) among older people with Down syndrome.
Frank Buckley is at
Down Syndrome Education International,
Portsmouth, Hampshire, UK.
Original research paper
- Zigman WB, Schupf N, Jenkins EC, Urv TK, Tycko B, Silverman W. Cholesterol
level, statin use and Alzheimer's disease in adults with Down syndrome. Neuroscience Letters. 2007;416:279-284.
Further research
- Bush A, Beail N. Risk factors for dementia in people with Down syndrome: Issues
in assessment and diagnosis. American Journal on Mental Retardation.
2004;109(2):83-97.
- Puglielli L, Tanzi RE, Kovacs DM. Alzheimer's disease: the cholesterol
connection. Nature Neuroscience. 2003;6(4):345-351.
Further reading
- Holland T, Benton M. Ageing and its consequences for people with Down's syndrome
- A guide for parents and carers. London, UK: Down's Syndrome Association; 2004.
Available from:
www.downs-syndrome.org.uk/pdfs/ageing%20&%20consequences.pdf
- Chicoine B, McGuire D. Adults with Down syndrome: Specialty clinic perspectives.
In: Janicki MP, Dalton AJ, editors. Dementia and aging adults with intellectual
disabilities: A handbook. Routledge; 1998. Available from:
www.ds-health.com/adults.htm