An Initial Empirical Operationalization of the Earliest Stages of the Alzheimer’s Continuum

Abstract

Purpose: The Alzheimer’s Continuum (AC) includes 2 preclinical stages defined by subjective cognitive complaints, transitional cognitive declines, and neurobehavioral symptoms. Operationalization of these stages is necessary for them to be applied in research. Methods: Cognitively normal individuals with known amyloid biomarker status were selected from the National Alzheimer’s Coordinating Center Uniform Data Set. Participants and their caregivers provided information on subjective cognitive complaints, neurobehavioral features, and objective cognitive functioning. Patients: The sample included 101 amyloid positive (A+) and 447 amyloid negative (A−) individuals. Results: Rates of subjective cognitive complaints (A+: 34.90%, A−: 29.90%) and neurobehavioral symptoms (A+: 22.40%, A−: 22.40%) did not significantly differ between A+/− individuals. However, the frequency of transitional cognitive decline was significantly higher among A+ (38.00%) than A− participants (24.90%). We explored various empirical definitions for defining the early stages of the AC among A+ participants. Rates of classification into AC stage 1 versus AC stage 2 varied depending on the number of symptoms required: 57.40% versus 42.60% (1 symptom), 28.70% versus 71.30% (2 symptoms), and 6.90% versus 93.10% (all 3 symptoms). Conclusion: The presence of 2 of the proposed symptom classes to separate AC stage 2 from stage 1 seems to provide a good empirical balance.

Dispersion-based cognitive intra-individual variability in dementia with Lewy bodies.

“…Notably, IIV-d remained a statistically significant predictor of diagnostic status even when clinician-rated cognitive fluctuations were included in the model, suggesting that IIV-d and clinician-rated cognitive fluctuations capture related but distinct elements of cognitive fluctuations. This finding aligns with previous research showing that subjective and objective measurements of cognition overlap but provide uniquely useful information for purposes of differential diagnosis, disease staging, and prognosis (Kiselica, Kaser, & Benge, 2021). This result also converges well with evidence that IIV-I and clinician-rated cognitive fluctuations have distinct yet overlapping variance (Walker et al, 2000).…”

Empirically defining the preclinical stages of the Alzheimer's continuum in the Alzheimer's Disease Neuroimaging Initiative

“…9,14 Subjective cognitive decline To our knowledge, this is the first study to classify positivity for SCD by using a demographically adjusted normative cut-off based on a psychometric instrument. This approach is likely preferable to simple yes/no assessments of SCD that have been employed in previous research, 40,51 as psychometric instruments tend to capture multifaceted aspects of SCD, 52 in addition to accounting for the influence of potentially confounding demographic factors on symptom presentations. Furthermore, using a normative approach may reduce false positives, as 71% of healthy older adults have reported at least some subjective cognitive symptoms.…”

“…Individuals were categorized as having clinically significant self‐reported depression if their summed score on the Geriatric Depression Scale was ≥5 39 . Participants were labelled as having an NBS if they had any clinician‐rated or participant‐reported NBS, replicating previous procedures 40 …”

“…clinician-rated or participant-reported NBS, replicating previous procedures. 40 Categorizing AC stages 1 and 2 Cognitively unimpaired, amyloid-positive participants were coded into AC stage 2 if they were positive for any one of the TCD, SCD, or NBS symptom classes. In contrast, if participants were negative for all three categories they were placed into AC stage 1.…”

Common Fatal Neurodegenerative Diseases Revisited: Beyond Age, Comorbidities, and Devastating Terminal Neuropathology There Is Hope With Prevention

“…The issue of preclinical stage definition is not easy for youngsters, in fact, is not easy in elderly populations where preclinical stage empirical definition of the Alzheimer's continuum is going on right now as The National Institute on Aging and the Alzheimer's Association published new research criteria defining the Alzheimer's continuum (AC) by the presence of amyloid-β biomarkers ( 46 ). Focusing on amyloid-β biomarkers is interesting given that in our studies with subjects ≤ 40 y, pTau is the main and foremost abnormal protein encountered even in toddlers while A β phases I and II remain with minimal changes for the first four decades of life ( 17 ).…”