Patterns of cognitive domain abnormalities enhance discrimination of dementia risk prediction: The ARIC study

Abstract

Introduction: The contribution of neuropsychological assessments to risk assessment for incident dementia is underappreciated.

Methods: We analyzed neuropsychological testing results in dementia-free participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined associations of index domain-specific neuropsychological test performance with incident dementia using cumulative incidence curves and Cox proportional hazards models.

Results: Among 5296 initially dementia-free participants (mean [standard deviation] age of 75.8 [5.1] years; 60.1% women, 22.2% Black) over a median follow-up of 7.9 years, the covariate-adjusted hazard ratio varied substantially depending on the pattern of domain-specific performance and age, in an orderly manner from single domain language abnormalities (lowest risk) to single domain executive or memory abnormalities, to multidomain abnormalities including memory (highest risk).

Discussion: By identifying normatively defined cognitive abnormalities by domains based on neuropsychological test performance, there is a conceptually orderly and age-sensitive spectrum of risk for incident dementia that provides valuable information about the likelihood of progression.

Highlights: Domain-specific cognitive profiles carry enhanced prognostic value compared to mild cognitive impairment. Single-domain non-amnestic cognitive abnormalities have the most favorable prognosis. Multidomain amnestic abnormalities have the greatest risk for incident dementia. Patterns of domain-specific risks are similar by sex and race.

Keywords: incident dementia; mild cognitive impairment; neuropsychological testing.

FIGURE 1

The Atherosclerosis Risk in Communities (ARIC) study, 1987–2020: flowchart of participants adjudicated as dementia free in 2011–2013 who were selected for analysis. MD, Maryland; MN, Minnesota; NCS, Neurocognitive Study.

FIGURE 2

Cumulative incidence curves of incident dementia with death as a competing risk by single and multiple cognitive domains: Atherosclerosis Risk in Communities Neurocognitive Study (ARIC‐NCS), 2011–2020 (N = 5296). Dementia diagnosis was determined by an adjudicated review of in‐person cognitive examinations, telephone interviews, informant interviews, hospitalization records, and death certificates. Diagnosis date based on the last clinical examination or phone‐based assessment. If dementia was ascertained from a telephone interview, informant interview, hospitalization record, or death certificate, the date was defined as 180 days prior to the documented incident or interview. A, All patterns of cognitive domain impairment. B, Language domain impairment at different levels of z score abnormalities. C, Executive domain impairment at different levels of z score abnormalities. D, Memory domain impairment at different levels of z score abnormalities.

FIGURE 3

Cumulative incidence curves of incident dementia by single cognitive domains at z score threshold of −1.5 stratified by median age plus relative excess risk due to interaction with age above median: Atherosclerosis Risk in Communities Neurocognitive Study (ARIC‐NCS), 2011–2020 (N = 5296). Column A: language domain impairment; Column B: executive domain impairment; Column C: memory domain impairment. Top row: cumulative incidence functions of dementia in ARIC NCS that treat death as a competing risk stratified by the median age of 75 years old. Bottom row: hazard ratios for the relative excess risk due to interactions with age relative to the sample median calculated from Cox proportional hazards regression models that adjusted for sex, race‐center, and education. 95% confidence intervals were generated using percentile bootstrapping with 1000 samples.

FIGURE 4

Cumulative incidence curves of incident dementia by single cognitive domains at z score threshold of −1.5 stratified by race or sex: Atherosclerosis Risk in Communities Neurocognitive Study (ARIC‐NCS), 2011–2020 (N = 5296). Column A: language domain impairment; Column B: executive domain impairment; Column C: memory domain impairment. Top row: cumulative incidence functions of dementia in ARIC NCS that treat death as a competing risk stratified by race. Bottom row: cumulative incidence functions of dementia in ARIC NCS that treat death as a competing risk stratified by sex.

FIGURE 5

Receiver operating characteristic curves for incident dementia: Atherosclerosis Risk in Communities Neurocognitive Study (ARIC‐NCS), 2011–2020 (N = 5296). Time‐dependent receiver operating characteristic curves and area under the curve estimates for selected patterns of domain abnormalities generated from cause‐specific, Cox proportional hazards regression models that used censoring weights estimate diagnostic accuracy at 2, 4, 6, and 8 years after the index visit in 2011–2013. The concordance statistics were computed using Harrell's method.