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25 August 2001. Two apparently contradictory reports in the August 11 Lancet have
injected new fuel into the debate about the role of inflammation in Alzheimer's
disease.
In the first study, Willem Van Gool at the Academic Medical Center, Amsterdam,
and colleages, tested the antiinflammatory drug hydroxychloroquine in a placebo-controlled
trial of 168 patients with early AD. Over an 18-month period, the drug failed
to slow disease progression as judged by cognitive function and deterioration
in the patients' daily routines.
In the second study, Richard Banati and colleagues at the Hammersmith Hospital,
London, used positron emission topography scans of patients with probable AD
to estimate binding of the R-enantiomer of the ligand PK11195. The ligand serves
as an in vivo marker of activated microglia, a normally dormant population of
brain macrophages that are thought to mediate the inflammatory response. The
researchers found significantly increased binding in the AD group compared to
age-matched controls. Areas most affected included the inferior and middle temporal
gyri, amygdala, and the inferior parietal lobe. Greater microglial activation
was seen in the left hemisphere. In follow-up MRI scans conducted over a one- to two-year period, the researchers found that areas with greatest (R)-PK11195 binding
atrophied fastest, suggesting that microglial activation had contributed to
disease progression.
In an accompanying commentary, Roy Jones of St Martins Hospital, Bath, points
out that the key factor in resolving these and other equivocal data on Alzheimer's
and inflammation may be time, in that antiinflammatory drugs may have prophylactic
benefits but may be ineffective once the disease has progressed even to early
stages.-Tom Fagan.
Reference:Van Gool WA, Weinstein HC, Scheltens P, Walstra GJ, Scheltens PK. Effect of hydroxychloroquine on progression of dementia in early Alzheimer's disease: an 18-month randomised, double-blind, placebo-controlled study. Lancet. 2001 Aug 11;358(9280):455-60. Abstract
Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB. In-vivo measurement of activated microglia in dementia.
Lancet 2001 Aug 11;358(9280):461-7. Abstract
Jones RW. Inflammation and Alzheimer's disease. Lancet 2001 Aug 11;358(9280):436-7. Abstract
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Effect of hydroxychloroquine on progression of dementia in early Alzheimer's disease: an 18-month randomised, double-blind, placebo-controlled study.
