Signs of brain impairment appeared as early as 9 years before people received a diagnosis for Alzheimer's or other dementia-related diseases, an analysis of U.K. Biobank data showed.
For several neurodegenerative syndromes, cognitive and functional changes were spotted in baseline assessments 5 to 9 years before diagnosis, reported Timothy Rittman, BMBS, BMedSci, PhD, of the University of Cambridge in England, and co-authors in Alzheimer's & Dementia.
The findings raise the possibility that at-risk people may be screened to identify who could benefit from interventions or be candidates for clinical trials, the researchers suggested.
"This research gives us a window of opportunity to intervene very early in the disease process of Alzheimer's disease and other types of dementia and neurodegenerative diseases," Rittman told MedPage Today.
"Before now we haven't been sure how early changes are detectable," he said. "Our study has found that it is possible to detect subtle changes 5 to 10 years before a diagnosis, meaning that it could be possible to screen people very early."
"Catching people early means they can be recruited to trials of prevention strategies and new drugs to slow down the disease, at a time when those interventions are most likely to be effective," Rittman added.
The U.K. Biobank study included people ages 40 to 69 years recruited between 2006 and 2010 from the general population.
Rittman and colleagues assessed baseline cognitive and functional measures in 2,778 participants who subsequently developed Alzheimer's, 2,370 who developed Parkinson's, 211 who developed frontotemporal dementia (FTD), 133 who developed progressive supranuclear palsy (PSP), 40 who developed dementia with Lewy bodies (DLB), and 73 who developed multiple system atrophy (MSA).
The researchers compared these individuals against baseline data from 493,735 Biobank controls who were not diagnosed later with a neurodegenerative diagnosis. Cognitive and functional scores were regressed against time to diagnosis, adjusting for effects of age.
Dates of diagnoses were collected from hospital inpatient and primary care records, death certificates, and self-reports. Mean years to diagnosis from baseline ranged from 8.3±3.0 for Alzheimer's disease to 4.7±2.1 for DLB.
Extensive differences in all cognitive assessments and some physical measures emerged in pre-Alzheimer's participants. People who subsequently developed Alzheimer's scored worse than controls on fluid intelligence, reaction time, numeric memory, prospective memory, and pair-matching.
Similar trends were seen for participants who developed FTD. These findings were in line with data about pre-symptomatic cognitive decline in familial mutation carriers of Alzheimer's or FTD, Rittman and co-authors noted.
People who developed Alzheimer's also were more likely to have had a fall in the previous 12 months than controls. People who developed PSP were more than twice as likely as controls to have had a fall.
Pre-Parkinson's individuals had preserved pre-symptomatic cognition and good evidence of preserved outcomes on some measures. Pre-MSA and pre-PSP groups showed a rapid functional decline in risk of falls and in overall health ratings leading up to the time of diagnosis.
"Our approach can form the basis for pre-diagnostic cognitive and functional screening to recruit into trials of disease prevention and disease-modifying therapies for neurodegenerative diseases," Rittman and co-authors observed.
"A screening panel based on cognition and function could be followed by disease-specific biomarkers to further improve risk stratification," they suggested.
Analyses of several groups of patients were limited by smaller sample sizes. "In DLB, this partly reflected the recording of the diagnosis in the U.K. Biobank, as it was only possible to search for DLB within the primary care data set," the researchers pointed out.
"Although the U.K. Biobank is population-based, it is biased toward a population with a lower risk of disease in general, and is not representative of ethnic and socioeconomic diversity in the United Kingdom," they acknowledged.
In addition, the midlife age range of the cohort may exclude ages when some risk factors for neurodegenerative diseases are strong.
Disclosures
The research was funded by the Medical Research Council with support from the NIHR Cambridge Biomedical Research Center.
Primary Source
Alzheimer's & Dementia
Source Reference: Swaddiwudhipong N, et al "Pre-diagnostic cognitive and functional impairment in multiple sporadic neurodegenerative diseases" Alzheimer's Dement 2022; DOI: 10.1002/alz.12802.