Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia

Abstract

Objective: To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans.Methods: A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants (55% African American and 61% female) aged 65 years and older residing in 4 Chicago neighborhoods. Time before AD dementia diagnosis was categorized into 6 groups corresponding to data collection periods: 0.1-0.9, 1.0-3.9, 4.0-6.9, 7.0-9.9, 10.0-12.9, and 13.0-17.9 years.Results: Of 2,125 participants without clinical AD dementia, 442 (21%) developed clinical AD dementia over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of AD dementia over the duration of the study. The magnitude of association between composite cognitive test score and development of AD dementia increased from an odds ratio of 3.39 (95% confidence interval 1.72, 6.67; p , 0.001) at 13.0-17.9 years to 9.84 (95% confidence interval 7.41, 13.06; p , 0.001) at 0.1-0.9 years, per SD increment. These associations were consistently larger among European Americans than among African Americans. Performance on individual cognitive tests of episodic memory, executive function, and global cognition also significantly predicted the development of AD dementia, with associations exhibiting a similar trend over 18 years. Because of the lack of effective treatments for Alzheimer disease (AD) dementia, early preventive efforts may be more effective in slowing preclinical manifestation of AD dementia. Conclusions:1,2 As a consequence, the long duration of preclinical AD dementia has been a major point of emphasis.3-5 Although our direct knowledge of the preclinical sequences and interrelations of cognitive and pathologic events are limited, pathologic events are generally thought to begin much earlier than clinical ones.6,7 Imaging-based studies suggest an initial deficiency in limbic regions of the brain affecting episodic memory in the early stages of the disease, 8,9 that progresses to the cortical regions of the brain followed by other cognitive symptoms, and an AD dementia syndrome is noticed. [10][11][12] Much of this knowledge is from investigations confined to clinical settings rather than from the general population.

Tau oligomers in cerebrospinal fluid in Alzheimer's disease

“…Prior to the manifestation of symptoms and clinical diagnosis, the neurodegenerative processes have already progressed to a relatively advanced stage with marked synaptic loss and neuronal damage 3. A recent study by Rajan et al has shown that impairment in cognition starts almost 18 years before AD dementia could be clinically diagnosed 4. The distinction between memory decline due to the normal course of aging and early stage AD dementia is so ambiguous that the category of mild cognitive impairment (MCI) has been developed to better characterize the earliest signs of AD 5.…”

The Impact of Depression and Apathy on Sensory Language

“…Alzheimer's disease is apparent through lexical repetition, marked by smaller, higher frequency vocabulary (Garrard et al, 2005), and can be seen in people's writing 10 -12 years before the disease is diagnosed (Rajan et al, 2015). Iris…”

“…Garrard et al, 2005;Van Velzen & Garrard, 2008;Lancashire & Hirst, 2009;Le, 2010;Le et al, 2011) and political figures (Garrard, 2009) has highlighted that Alzheimer's disease may be apparent years or even decades before anyone becomes aware of any symptoms of cognitive deterioration. A recent study suggests that Alzheimer's disease can be seen in people's writing 10 -12 years before the disease is diagnosed (Rajan et al, 2015). To test the hypothesis that thought and language are impacted by depression and apathy and revealed in a person's writing style 12 years before a formal diagnosis of Alzheimer's disease presents, we draw on earlier studies of AD.…”

Gwas Meta-Analysis Reveals Novel Loci And Genetic Correlates For General Cognitive Function: A Report From The Cogent Consortium

“…Human personality traits such as openness to new experiences 20 and negative affect 21 are, respectively, associated with better and worse neurocognitive performance. Individuals with debilitating neurological illnesses such as Parkinson's disease 22,23 and (by definition) the dementia spectrum including Alzheimer's disease 24 also suffer from marked neurocognitive impairments. Further, early life cognitive performance can predict long-term development of illness, 25 including mortality.…”