Mild Behavioral Impairment and Subjective Cognitive Decline Predict Cognitive and Functional Decline

Abstract

Background: Mild behavioral impairment (MBI) and subjective cognitive decline (SCD) are dementia risk states, and potentially represent neurobehavioral and neurocognitive manifestations, respectively, of early stage neurodegeneration. Both MBI and SCD predict incident cognitive decline and dementia, are associated with known dementia biomarkers, and are both represented in the NIA-AA research framework for AD in Stage 2 (preclinical disease). Objective: To assess the associations of MBI and SCD, alone and in combination, with incident cognitive and functional decline in a population of older adults. We tested the hypothesis that MBI and SCD confer additive risk for decline. Methods: Cognitively normal participants were followed up annually at Alzheimer’s Disease Centers. Logistic regression assessed the relationship between baseline classification (MBI-SCD-, MBI-SCD+, MBI+SCD-, or MBI+SCD+) and 3-year outcome. Results: Of 2,769 participants (mean age=76), 1,536 were MBI-SCD-, 254 MBI-SCD+, 743 MBI+SCD-, and 236 MBI+SCD+. At 3 years, 349 (12.6%) declined to CDR >0, including 23.1% of the MBI+group, 23.5% of the SCD+group, and 30.9% of the intersection group of both MBI+and SCD+participants. Compared to SCD-MBI-, we observed an ordinal progression in risk (ORs [95% CI]): 3.61 [2.42–5.38] for MBI-SCD+ (16.5% progression), 4.76 [3.57–6.34] for MBI+SCD- (20.7%), and 8.15 [5.71–11.64] for MBI+SCD+(30.9%). Conclusion: MBI and SCD together were associated with the greatest risk of decline. These complementary dementia risk syndromes can be used as simple and scalable methods to identify high-risk patients for workup or for clinical trial enrichment.

Mild Behavioral Impairment Is Associated With Atrophy of Entorhinal Cortex and Hippocampus in a Memory Clinic Cohort

“…MBI describes new-onset and persistent NPS in non-demented older adults (reflecting a change from baseline patterns of behavior), as an at-risk state for incident cognitive decline and dementia. MBI can emerge not only in persons with MCI but also in cognitively normal (CN) older adults, in whom MBI is associated with a greater risk of incident cognitive decline and dementia ( Taragano et al, 2018 ; Matsuoka et al, 2019 ; Ismail et al, 2021 ). MBI (assessed with the Neuropsychiatric Inventory) was highly prevalent in both clinical and community-based cohorts of non-demented older adults ( Mortby et al, 2018 ; Sheikh et al, 2018 ).…”

Cognitive profile of mild behavioral impairment in Brain Health Registry participants

“…The findings do suggest that a simple informant reported behavioral measure completed via an online portal might be a relevant addition to neuropsychological testing, warranting further study in BHR. In other work, MBI+ status has demonstrated significant and meaningful associations with incident cognitive decline and dementia across several studies, settings, and populations [20][21][22][23][24][25][26] . Thus, while convergent with tests of memory and executive function, behavioral and cognitive markers of risk may be distinct, potentially offering complementary measures of risk.…”

“…These convergent findings support leveraging online cognitive and behavioral measures to explore dementia risk. In a recent study of National Alzheimer Coordinating Center data, the combination of informant-reported MBI and subjective cognitive decline (SCD) had a greater risk of incident cognitive and functional decline at three years compared to either MBI or SCD alone 24 . Further, in a subsequent study, those with SCD and MBI together had a shorter median time to incident MCI compared to those with SCD in the absence of MBI 48 .…”

“…Mild behavioral impairment (MBI) is a pre-dementia neurobehavioral syndrome characterized by the de novo emergence and persistence of NPS in older adults representing a change from longstanding patterns of behavior 12 . MBI is associated with amyloid, tau, and neurodegeneration [13][14][15][16][17][18][19] , and a greater risk of incident cognitive decline and dementia [20][21][22][23][24][25][26] .…”

Sex differences in the association of mild behavioral impairment with cognitive aging

“…8 MBI is associated with faster cognitive and functional decline. 9,10 Also individual NPS, especially anxiety and irritability, have been found to be related to cognitive decline. 11,12 Moreover, several studies report links between MBI and neurobiological markers, such as higher β-amyloid deposition, tau pathology, and neurodegeneration in pre-dementia population 13-15 .…”