Dataset Information

Age-specific population frequencies of cerebral ?-amyloidosis and neurodegeneration among people with normal cognitive function aged 50-89 years: a cross-sectional study.

ABSTRACT: As preclinical Alzheimer's disease becomes a target for therapeutic intervention, the overlap between imaging abnormalities associated with typical ageing and those associated with Alzheimer's disease needs to be recognised. We aimed to characterise how typical ageing and preclinical Alzheimer's disease overlap in terms of ?-amyloidosis and neurodegeneration.We measured age-specific frequencies of amyloidosis and neurodegeneration in individuals with normal cognitive function aged 50-89 years. Potential participants were randomly selected from the Olmsted County (MN, USA) population-based study of cognitive ageing and invited to participate in cognitive and imaging assessments. To be eligible for inclusion, individuals must have been judged clinically to have no cognitive impairment and have undergone amyloid PET, (18)F-fluorodeoxyglucose ((18)F-FDG) PET, and MRI. Imaging results were obtained from March 28, 2006, to Dec 3, 2013. Amyloid status (positive [A(+)] or negative [A(-)]) was determined by amyloid PET with (11)C Pittsburgh compound B. Neurodegeneration status (positive [N(+)] or negative [N(-)]) was determined by an Alzheimer's disease signature (18)F-FDG PET or hippocampal volume on MRI. We determined age-specific frequencies of the four groups (amyloid negative and neurodegeneration negative [A(-)N(-)], amyloid positive and neurodegeneration negative [A(+)N(-)], amyloid negative and neurodegeneration positive [A(-)N(+)], or amyloid positive and neurodegeneration positive [A(+)N(+)]) cross-sectionally using multinomial regression models. We also investigated associations of group frequencies with APOE ?4 status (assessed with DNA extracted from blood) and sex by including these covariates in the multinomial models.The study population consisted of 985 eligible participants. The population frequency of A(-)N(-) was 100% (n=985) at age 50 years and fell to 17% (95% CI 11-24) by age 89 years. The frequency of A(+)N(-) increased to 28% (24-32) at age 74 years, then decreased to 17% (11-25) by age 89 years. The frequency of A(-)N(+) increased from age 60 years, reaching 24% (16-34) by age 89 years. The frequency of A(+)N(+) increased from age 65 years, reaching 42% (31-52) by age 89 years. The results from our multinomial models suggest that A(+)N(-) and A(+)N(+) were more frequent in APOE ?4 carriers than in non-carriers and that A(+)N(+) was more, and A(+)N(-) less frequent in men than in women.Accumulation of amyloid and neurodegeneration are nearly inevitable by old age, but many people are able to maintain normal cognitive function despite these imaging abnormalities. Changes in the frequency of amyloidosis and neurodegeneration with age, which seem to be modified by APOE ?4 and sex, suggest that pathophysiological sequences might differ between individuals.US National Institute on Aging and Alexander Family Professorship of Alzheimer's Disease Research.

SUBMITTER: Jack CR

PROVIDER: S-EPMC4324499 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Age-specific population frequencies of cerebral β-amyloidosis and neurodegeneration among people with normal cognitive function aged 50-89 years: a cross-sectional study.

Jack Clifford R CR Wiste Heather J HJ Weigand Stephen D SD Rocca Walter A WA Knopman David S DS Mielke Michelle M MM Lowe Val J VJ Senjem Matthew L ML Gunter Jeffrey L JL Preboske Gregory M GM Pankratz Vernon S VS Vemuri Prashanthi P Petersen Ronald C RC

The Lancet. Neurology 20140904 10

<h4>Background</h4>As preclinical Alzheimer's disease becomes a target for therapeutic intervention, the overlap between imaging abnormalities associated with typical ageing and those associated with Alzheimer's disease needs to be recognised. We aimed to characterise how typical ageing and preclinical Alzheimer's disease overlap in terms of β-amyloidosis and neurodegeneration.<h4>Methods</h4>We measured age-specific frequencies of amyloidosis and neurodegeneration in individuals with normal cog ...[more]

PMID: 25201514

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Project description:BACKGROUND:A new classification for biomarkers in Alzheimer's disease and cognitive ageing research is based on grouping the markers into three categories: amyloid deposition (A), tauopathy (T), and neurodegeneration or neuronal injury (N). Dichotomising these biomarkers as normal or abnormal results in eight possible profiles. We determined the clinical characteristics and prevalence of each ATN profile in cognitively unimpaired individuals aged 50 years and older. METHODS:All participants were in the Mayo Clinic Study of Aging, a population-based study that uses a medical records linkage system to enumerate all individuals aged 50-89 years in Olmsted County, MN, USA. Potential participants are randomly selected, stratified by age and sex, and invited to participate in cognitive assessments; individuals without medical contraindications are invited to participate in brain imaging studies. Participants who were judged clinically as having no cognitive impairment and underwent multimodality imaging between Oct 11, 2006, and Oct 5, 2016, were included in the current study. Participants were classified as having normal (A-) or abnormal (A+) amyloid using amyloid PET, normal (T-) or abnormal (T+) tau using tau PET, and normal (N-) or abnormal (N+) neurodegeneration or neuronal injury using cortical thickness assessed by MRI. We used the cutoff points of standard uptake value ratio (SUVR) 1·42 (centiloid 19) for amyloid PET, 1·23 SUVR for tau PET, and 2·67 mm for MRI cortical thickness. Age-specific and sex-specific prevalences of the eight groups were determined using multinomial models combining data from 435 individuals with amyloid PET, tau PET, and MRI assessments, and 1113 individuals who underwent amyloid PET and MRI, but not tau PET imaging. FINDINGS:The numbers of participants in each profile group were 165 A-T-N-, 35 A-T+N-, 63 A-T-N+, 19 A-T+N+, 44 A+T-N-, 25 A+T+N-, 35 A+T-N+, and 49 A+T+N+. Age differed by ATN group (p<0·0001), ranging from a median 58 years (IQR 55-64) in A-T-N- and 57 years (54-64) in A-T+N- to a median 80 years (75-84) in A+T-N+ and 79 years (73-87) in A+T+N+. The number of APOE ?4 carriers differed by ATN group (p=0·04), with carriers roughly twice as frequent in each A+ group versus the corresponding A- group. White matter hyperintensity volume (p<0·0001) and cognitive performance (p<0·0001) also differed by ATN group. Tau PET and neurodegeneration biomarkers were discordant in most individuals who would be categorised as stage 2 or 3 preclinical Alzheimer's disease (A+T+N-, A+T-N+, and A+T+N+; 86% at age 65 years and 51% at age 80 years) or with suspected non-Alzheimer's pathophysiology (A-T+N-, A-T-N+, and A-T+N+; 92% at age 65 years and 78% at age 80 years). From age 50 years, A-T-N- prevalence declined and A+T+N+ and A-T+N+ prevalence increased. In both men and women, A-T-N- was the most prevalent until age late 70s. After about age 80 years, A+T+N+ was most prevalent. By age 85 years, more than 90% of men and women had one or more biomarker abnormalities. INTERPRETATION:Biomarkers of fibrillar tau deposition can be included with those of ?-amyloidosis and neurodegeneration or neuronal injury to more fully characterise the heterogeneous pathological profiles in the population. Both amyloid- dependent and amyloid-independent pathological profiles can be identified in the cognitively unimpaired population. The prevalence of each ATN group changed substantially with age, with progression towards more biomarker abnormalities among individuals who remained cognitively unimpaired. FUNDING:National Institute on Aging (part of the US National Institutes of Health), the Alexander Family Professorship of Alzheimer's Disease Research, the Mayo Clinic, and the GHR Foundation.

Project description:BackgroundColorectal cancer (CRC) screening is effective for early detection of CRC, particularly for males aged 50 or above. However, the rate of participation in the screening program is still low. This study was to examine knowledge, attitudes, and practice toward CRC and its screening and explored their associated factors.MethodsA descriptive cross-sectional study was conducted in a convenience sample of adults aged 50-75 years without cognitive problems, who were recruited at multi-elderly centers in Hong Kong. A questionnaire was used to measure knowledge, attitudes, and practice (KAP) towards CRC and its screening.ResultsThe total of 300 Chinese people included 147 (49.0%) males with a mean age of 58.72 (SD 6.91) years old. This study population had good knowledge and practice, as well as very good attitudes toward CRC and its screening. The multivariate regression results showed that receiving insurance coverage was the most significant factor positively associated with knowledge, attitudes, and practice. Other than this, lower educational level had significant negative association with knowledge and practice. Having self-sufficient financial support and receiving screening program information had positive associations with knowledge.ConclusionPeople who are receiving insurance coverage have better KAP towards CRC and its screening. This indicates that they can receive adequate information about the screening procedure from their insurance agents and receive financial support under their insurance coverage. Therefore, they are more willing to participate in the screening program. Other factors, including having good self-sufficient financial support and receiving adequate information about CRC and its screening, significantly enhance knowledge. Based on the relationships among KAP, knowledge enhancement can improve attitude and practice in participating in the CRC screening program. Those who attained lower education should receive more attention. In this sense, adequate financial support from health insurance or subsidies from the government can increase an individual's willingness to participate in the CRC screening, particularly those at a low socioeconomic level. Educational programs should be promoted to enhance knowledge about CRC and its screening, especially to those who attained lower education levels.

Dataset Information

Age-specific population frequencies of cerebral ?-amyloidosis and neurodegeneration among people with normal cognitive function aged 50-89 years: a cross-sectional study.

Publications

Age-specific population frequencies of cerebral β-amyloidosis and neurodegeneration among people with normal cognitive function aged 50-89 years: a cross-sectional study.

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