Alzheimer’s disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies2. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels3, structural and functional magnetic resonance imaging4 and the recent use of brain amyloid imaging5 or inflammaging6, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer’s disease with the required sensitivity and specificity7. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer’s disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer’s disease within a 2–3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer’s disease.

Objective The oldest old are the fastest growing segment of the US population, and accurate estimates of dementia incidence in this group are crucial for healthcare planning. Although dementia incidence doubles every 5 years from ages 65 to 90 years, it is unknown if this exponential increase continues past age 90 years. Here, we estimate age- and sex-specific incidence rates of all-cause dementia in people aged 90 years and older, including estimates for centenarians. Methods Participants are from The 90+ Study, a population-based longitudinal study of aging and dementia. Three hundred thirty nondemented participants aged 90 years and older at baseline were followed between January 2003 and December 2007. Age- and sex-specific incidence rates of all-cause dementia were estimated by person-years analysis. Results The overall incidence rate of all-cause dementia was 18.2% (95% confidence interval [CI], 15.3-21.5) per year and was similar for men and women (risk ratio, 0.94; 95% CI, 0.65–1.37). Rates increased exponentially with age from 12.7% per year in the 90–94-year age group, to 21.2% per year in the 95–99-year age group, to 40.7% per year in the 100+-year age group. The doubling time based on a Poisson regression was 5.5 years. Interpretation Incidence of all-cause dementia is very high in people aged 90 years and older and continues to increase exponentially with age in both men and women. Projections of the number of people with dementia should incorporate this continuing increase of dementia incidence after age 90 years. Our results foretell the growing public health burden of dementia in an increasingly aging population.

In a very large sample of participants aged 90 and older, prevalence of all-cause dementia doubled every 5 years for women but not men.