Prevalence of preclinical Alzheimer disease: Comparison of current classification systems.
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ABSTRACT: Objective
To determine the prevalence of preclinical Alzheimer disease (AD) according to current classification systems by examining CSF from a representative general population sample of 70-year-olds from Gothenburg, Sweden.Method
The sample was derived from the population-based H70 Gothenburg Birth Cohort Studies in Gothenburg, Sweden. The participants (n = 322, age 70 years) underwent comprehensive neuropsychiatric, cognitive, and somatic examinations. CSF levels of β-amyloid (Aβ)42, Aβ40, total tau, and phosphorylated tau were measured. Preclinical AD was classified according to criteria of the A/T/N system, Dubois 2016, National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, and International Working Group-2 (IWG-2) criteria. Individuals with Clinical Dementia Rating score >0 were excluded, leaving 259 cognitively unimpaired individuals.Results
The prevalence of amyloid pathology was 22.8%, of total tau pathology was 33.2%, and of phosphorylated tau pathology was 6.9%. With the A/T/N system, the prevalence of A+/T-/N- was 13.1%, A+/T-/N+ was 7.3%, A+/T+/N+ was 2.3%, A-/T-/N+ was 18.9%, and A-/T+/N+ was 4.6%. When the Dubois criteria were applied, the prevalence of asymptomatic at risk for AD was 36.7% and of preclinical AD was 9.7%. With the NIA-AA criteria, the prevalence of stage 1 was 13.1% and stage 2 was 9.7%. With the IWG-2 criteria, the prevalence of asymptomatic at risk for AD was 9.7%. The APOE ε4 allele was associated with several of the categories. Men more often had total tau pathology, A+/T-/N+, preclinical AD according to Dubois 2016, asymptomatic at risk for AD according to the IWG-2 criteria, and NIA-AA stage 2.Conclusion
The prevalence of pathologic AD markers was very common (46%) in a representative population sample of 70-year-olds. The clinical implications of these findings need to be scrutinized further in longitudinal studies.
SUBMITTER: Kern S
PROVIDER: S-EPMC5952969 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceChanges in behavior and personality are 1 criterion for the diagnosis of dementia. It is unclear, however, whether such changes begin before the clinical onset of the disease.ObjectiveTo determine whether increases in neuroticism, declines in conscientiousness, and changes in other personality traits occur before the onset of mild cognitive impairment or dementia.Design, setting, and participantsA cohort of 2046 community-dwelling older adults who volunteered to participate in the Baltimore Longitudinal Study of Aging were included. The study examined personality and clinical assessments obtained between 1980 and July 13, 2016, from participants with no cognitive impairment at first assessment who were followed up for as long as 36 years (mean [SD], 12.05 [9.54] years). The self-report personality scales were not considered during consensus diagnostic conferences.Main outcomes and measuresChange in self-rated personality traits assessed in the preclinical phase of Alzheimer disease and other dementias with the Revised NEO Personality Inventory, a 240-item questionnaire that assesses 30 facets, 6 for each of the 5 major dimensions: neuroticism, extraversion, openness, agreeableness, and conscientiousness.ResultsOf the?2046 participants, 931 [45.5%] were women; mean (SD) age at first assessment was 62.56 (14.63) years. During 24?569 person-years, mild cognitive impairment was diagnosed in 104 (5.1%) individuals, and all-cause dementia was diagnosed in 255 (12.5%) participants, including 194 (9.5%) with Alzheimer disease. Multilevel modeling that accounted for age, sex, race, and educational level found significant differences on the intercept of several traits: individuals who developed dementia scored higher on neuroticism (??=?2.83; 95% CI, 1.44 to 4.22; P?<?.001) and lower on conscientiousness (??=?-3.34; 95% CI, -4.93 to -1.75; P?<?.001) and extraversion (??=?-1.74; 95% CI, -3.23 to -0.25; P?=?.02). Change in personality (ie, slope), however, was not significantly different between the nonimpaired and the Alzheimer disease groups (eg, neuroticism: ??=?0.00; 95% CI, -0.08 to 0.08; P?=?.91; conscientiousness: ??=?-0.06; 95% CI, -0.16 to 0.04; P?=?.24). Slopes for individuals who developed mild cognitive impairment (eg, neuroticism: ??=?0.00; 95% CI, -0.12 to 0.12; P?=?.98; conscientiousness: ??=?-0.09; 95% CI, -0.23 to 0.05; P?=?.18) and all-cause dementia (eg, neuroticism: ??=?0.02; 95% CI, -0.06 to 0.10; P?=?.49; conscientiousness: ??=?-0.08; 95% CI, -0.16 to 0.00; P?=?.07) were also similar to those for nonimpaired participants.Conclusions and relevanceNo evidence for preclinical change in personality before the onset of mild cognitive impairment or dementia was identified. These findings provide evidence against the reverse causality hypothesis and strengthen evidence for personality traits as a risk factor for dementia.
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