Levels of biomarkers in the CSF of patients with very mild dementia of the Alzheimer type are associated with a more rapid progression of cognitive deficits and dementia, according to a study in the May Archives of Neurology.
Barbara J. Snider, MD, PhD, of the Department of Neurology, Washington University School of Medicine in St. Louis, and colleagues analyzed 49 patients with a clinical diagnosis of very mild dementia of the Alzheimer type with a Clinical Dementia Rating (CDR) of 0.5 at the time of lumbar puncture.
All subjects were followed up for a mean of 3.5 years. Main outcome measures were baseline CSF levels of β-amyloid peptide 1-42 (Aβ 42), Aβ 40, tau, and phosphorylated tau at threonine 181 (ptau181), as well as rate of dementia progression as measured with use of the CDR sum of boxes (CDR-SB) score and psychometric performance.
The researchers found that the rate of dementia progression was significantly more rapid in individuals with lower baseline CSF Aβ 42 levels, higher tau or ptau181 levels, or high tau:Aβ 42 ratios. The annual change in the CDR-SB score was 1.1 for the lowest two tertiles of Aβ 42 values and 0.3 for the highest tertile of Aβ 42 values, according to Dr. Snider’s group.
“This study differs importantly from earlier studies in that we show that levels of biomarkers are strongly predictive of the actual rate of decline rather than with a dichotomous assessment of conversion/no conversion from mild impairment to diagnosed dementia of the Alzheimer type,” the investigators wrote.
“These findings are likely to have important implications for reducing the number of participants needed to show an effect in clinical trials for very mild dementia of the Alzheimer type and mild cognitive impairment and, ultimately, to assist in making treatment decisions as more invasive and potentially harmful disease-modifying treatments for Alzheimer’s disease become available,” Dr. Snider and colleagues concluded.