Alzheimer’s likely takes more than two decades to develop

A prospective study published in the April issue of The Lancet showed how beta-amyloid burden in the brain relates to the long-term progression of cognitive decline, cerebral atrophy and other indications of Alzheimer’s disease (AD). “Beta-amyloid deposition is slow and protracted, likely to extend for more than two decades,” the authors wrote.

“Such predictions of the rate of preclinical changes and the onset of the clinical phase of AD will facilitate the design and timing of therapeutic interventions aimed at modifying the course of this illness,” wrote Victor L. Villemagne, MD, of the Australian Imaging Biomarkers and Lifestyle Research Group, and colleagues.

The progression of amyloid accumulation plateaud over time, indicating to researchers that there was an extensive preclinical phase of Alzheimer’s disease development, or 17 years for amyloid deposition to reach positive-test levels using carbon-11-labelled Pittsburgh compound B (11C-PiB) PET imaging, slightly more than four years for atrophy of the hippocampus and 3.3 years of declining memory before patients reached a score of 1 in a standard rating of clinical dementia.

“There was an association between the rates of beta-amyloid deposition and memory decline in the healthy control and [mild cognitive impairment (MCI)] groups, and this association was even stronger in the healthy controls with high 11C-PiB retention, supporting the idea that beta-amyloid deposition is neither part of normal aging nor a benign process,” noted the authors. “Results from this study show, for what is to our knowledge the first time, an association between the rates of beta-amyloid deposition and memory decline in patients with AD, in whom faster deposition was significantly associated with faster memory decline.”

There was no significant relationship found between rates of beta-amyloid deposition and cortical gray matter atrophy in any of the groups, but the authors found a marked relationship between beta-amyloid deposition, hippocampal atrophy and memory decline for healthy controls. Respective measurements indicated that beta-amyloid accumulation is likely to have an impact on cognitive impairment as Alzheimer’s disease first develops.

“New proposed diagnostic criteria for AD incorporate the use of biomarkers, which show either the underlying pathogenesis by assessing beta-amyloid in the brain or [cerebral spinal fluid (CSF)], or synaptic and neuronal damage as indicated in reduced glucose metabolism, gray matter atrophy, or tau in CSF,” explained the authors. “Intra-individual changes in beta-amyloid deposition, brain atrophy, and cognitive decline provide a more accurate estimation of disease progression than inter-individual comparisons of groups. This approach is crucial in the assessment of cognitively unimpaired individuals.”

A total of 200 subjects, aged 55 to 89, were included in the study. There were 19 patients with AD, 36 participants considered to have MCI and 145 healthy controls recruited. Patients were examined initially and then every 18 months during the course of three to five years beginning in September 2004, each time with a neuropsychological evaluation, an MRI and 11C-PiB PET scan.

Those diagnosed with AD showed significantly more amyloid buildup after initial screening than those with mild cognitive impairment. At the first follow-up, 82 percent of participants showed increased amyloid burden in the brain.

According to longitudinal data analysis, researchers estimated that it takes a little more than 19 years with a mean annual increase of 0.043 standardized uptake value ratio for healthy controls to accumulate the levels of amyloid found in those with a positive AD diagnosis. According to the data, it would take a mean of 12 years for healthy controls with low amyloid deposition levels to get a positive 11C-PiB PET scan for amyloid accumulation.