scholarly journals Scores Obtained from a Simple Cognitive Test of Visuospatial Episodic Memory Performed Decades before Death Are Associated with the Ultimate Presence of Alzheimer Disease Pathology

2018 ◽  
Vol 45 (1-2) ◽  
pp. 79-90 ◽  
Author(s):  
Andrew C. Robinson ◽  
Roseanne McNamee ◽  
Yvonne S. Davidson ◽  
Michael A. Horan ◽  
Julie S. Snowden ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Test Scores ◽  
Apoe Genotype ◽  
Population Based ◽  
Cognitive Test ◽  
Cognitive State ◽  
Early Interventions ◽  
Braak Stage ◽  
The University ◽  
University Of Manchester

Background: Community- or population-based longitudinal studies of cognitive ability with a brain donation end point offer an opportunity to examine relationships between pathology and cognitive state prior to death. Discriminating the earliest signs of dementing disorders, such as Alzheimer disease (AD), is necessary to undertake early interventions and treatments. Methods: The neuropathological profile of brains donated from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, including CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) and Braak stage, was assessed by immunohistochemistry. Cognitive test scores collected 20 years prior to death were correlated with the extent of AD pathology present at death. Results: Baseline scores from the Memory Circle test had the ability to distinguish between individuals who developed substantial AD pathology and those with no, or low, AD pathology. Predicted test scores at the age of 65 years also discriminated between these pathology groups. The addition of APOE genotype further improved the discriminatory ability of the model. Conclusions: The results raise the possibility of identifying individuals at future risk of the neuropathological changes associated with AD over 20 years before death using a simple cognitive test. This work may facilitate early interventions, therapeutics and treatments for AD by identifying at-risk and minimally affected (in pathological terms) individuals.

scholarly journals Digital Technology Differentiates Graphomotor and Information Processing Speed Patterns of Behavior

2021 ◽  
Vol 82 (1) ◽  
pp. 17-32 ◽  
Author(s):  
Stacy L. Andersen ◽  
Benjamin Sweigart ◽  
Nancy W. Glynn ◽  
Mary K. Wojczynski ◽  
Bharat Thyagarajan ◽  
...  
Keyword(s):  
Information Processing ◽  
Physical Function ◽  
Digital Technology ◽  
Test Scores ◽  
Neuropsychological Test ◽  
Apoe Genotype ◽  
Digital Data ◽  
Cognitive Test ◽  
Digit Symbol Substitution Test ◽  
Information Processing Speed

Background: Coupling digital technology with traditional neuropsychological test performance allows collection of high-precision metrics that can clarify and/or define underlying constructs related to brain and cognition. Objective: To identify graphomotor and information processing trajectories using a digitally administered version of the Digit Symbol Substitution Test (DSST). Methods: A subset of Long Life Family Study participants (n = 1,594) completed the DSST. Total time to draw each symbol was divided into ‘writing’ and non-writing or ‘thinking’ time. Bayesian clustering grouped participants by change in median time over intervals of eight consecutively drawn symbols across the 90 s test. Clusters were characterized based on sociodemographic characteristics, health and physical function data, APOE genotype, and neuropsychological test scores. Results: Clustering revealed four ‘thinking’ time trajectories, with two clusters showing significant changes within the test. Participants in these clusters obtained lower episodic memory scores but were similar in other health and functional characteristics. Clustering of ‘writing’ time also revealed four performance trajectories where one cluster of participants showed progressively slower writing time. These participants had weaker grip strength, slower gait speed, and greater perceived physical fatigability, but no differences in cognitive test scores. Conclusion: Digital data identified previously unrecognized patterns of ‘writing’ and ‘thinking’ time that cannot be detected without digital technology. These patterns of performance were differentially associated with measures of cognitive and physical function and may constitute specific neurocognitive biomarkers signaling the presence of subtle to mild dysfunction. Such information could inform the selection and timing of in-depth neuropsychological assessments and help target interventions.

scholarly journals Influence of APOE genotype in primary age-related tauopathy

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Andrew C. Robinson ◽  
Yvonne S. Davidson ◽  
Federico Roncaroli ◽  
James Minshull ◽  
Phillip Tinkler ◽  
...  
Keyword(s):  
Apoe Genotype ◽  
Protein Isoforms ◽  
Elderly Subjects ◽  
Cognitively Impaired ◽  
Age Related ◽  
Dementia Research ◽  
Amyloid Aβ ◽  
The University ◽  
University Of Manchester ◽  
The Impact

AbstractThe term “Primary age-related tauopathy” (PART) was coined in 2014 to describe the common neuropathological observation of neurofibrillary tangles without associated beta-amyloid (Aβ) pathology. It is possible for PART pathology to be present in both cognitively normal and cognitively impaired individuals. Genetically, Apolipoprotein E (APOE) ε4 has been shown to occur less commonly in PART than in Alzheimer’s disease (AD). Here, we investigate the relationships between PART, AD and those pathologically normal for age, with an emphasis on APOE and cognition, using 152 selected participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age and the Manchester arm of the Brains for Dementia Research cohort. APOE genotype differed between PART and AD with APOE ε2 more common in the former and APOE ε4 more common in the latter. Individuals with definite PART were less likely to be cognitively impaired than those with AD and those with pathology considered pathologically normal for age. We postulate that the lack of Aβ in definite PART cases may be due either to an increased frequency of APOE ε2 or decreased frequency of APOE ε4 as their resulting protein isoforms have differing binding properties in relation to Aβ. Similarly, an increased frequency of APOE ε2 or decreased frequency of APOE ε4 may lead to decreased levels of cognitive impairment, which raises questions regarding the impact of Aβ pathology on overall cognition in elderly subjects. We suggest that it may be possible to use the increased frequency of APOE ε2 in definite PART to assist neuropathological diagnosis.

P.3.18 Cognitive test scores are lower in adolescent cigarette smokers compared to non-smokers: a population-based study

2008 ◽  
Vol 18 ◽  
pp. s77-s78
Author(s):  
N. Werbeloff ◽  
G. Lubin ◽  
S. Zarka ◽  
M. Shmushkevitch ◽  
E. Kravitz ◽  
...  
Keyword(s):  
Test Scores ◽  
Population Based ◽  
Cognitive Test ◽  
Cigarette Smokers ◽  
Population Based Study

scholarly journals Alzheimer risk loci and associated neuropathology in a population-based study (Vantaa 85+)

2018 ◽  
Vol 4 (1) ◽  
pp. e211 ◽  
Author(s):  
Mira Mäkelä ◽  
Karri Kaivola ◽  
Miko Valori ◽  
Anders Paetau ◽  
Tuomo Polvikoski ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Association Studies ◽  
Neurofibrillary Tangle ◽  
Snp Array ◽  
Population Based ◽  
Continuous Variable ◽  
Amyloid Angiopathy ◽  
Braak Stage ◽  
Genome Wide Association Studies ◽  
Population Based Study

ObjectiveTo test the association of distinct neuropathologic features of Alzheimer disease (AD) with risk loci identified in genome-wide association studies.MethodsVantaa 85+ is a population-based study that includes 601 participants aged ≥85 years, of which 256 were neuropathologically examined. We analyzed 29 AD risk loci in addition to APOE ε4, which was studied separately and used as a covariate. Genotyping was performed using a single nucleotide polymorphism (SNP) array (341 variants) and imputation (6,038 variants). Participants with Consortium to Establish a Registry for Alzheimer Disease (CERAD) (neuritic Aβ plaques) scores 0 (n = 65) vs score M + F (n = 171) and Braak (neurofibrillary tangle pathology) stages 0–II (n = 74) vs stages IV–VI (n = 119), and with capillary Aβ (CapAβ, n = 77) vs without (n = 179) were compared. Cerebral amyloid angiopathy (CAA) percentage was analyzed as a continuous variable.ResultsAltogether, 24 of the 29 loci were associated (at p < 0.05) with one or more AD-related neuropathologic features in either SNP array or imputation data. Fifteen loci associated with CERAD score, smallest p = 0.0002122, odds ratio (OR) 2.67 (1.58–4.49) at MEF2C locus. Fifteen loci associated with Braak stage, smallest p = 0.004372, OR 0.31 (0.14–0.69) at GAB2 locus. Twenty loci associated with CAA, smallest p = 7.17E-07, β 14.4 (8.88–20) at CR1 locus. Fifteen loci associated with CapAβ smallest p = 0.002594, OR 0.54 (0.37–0.81) at HLA-DRB1 locus. Certain loci associated with specific neuropathologic features. CASS4, CLU, and ZCWPW1 associated only with CAA, while TREM2 and HLA-DRB5 associated only with CapAβ.ConclusionsAD risk loci differ in their association with neuropathologic features, and we show for the first time distinct risk loci for CAA and CapAβ.

scholarly journals Association Between APOE Alleles and Change of Neuropsychological Tests in the Long Life Family Study

2021 ◽  
Vol 79 (1) ◽  
pp. 117-125
Author(s):  
Mengtian Du ◽  
Stacy L. Andersen ◽  
Nicole Schupf ◽  
Mary F. Feitosa ◽  
Megan S. Barker ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Test Scores ◽  
Healthy Aging ◽  
Family Study ◽  
Apoe Genotype ◽  
Cognitive Test ◽  
Cross Sectional ◽  
Long Life ◽  
E4 Allele

Background: The Long Life Family Study (LLFS) is a family based, prospective study of healthy aging and familial longevity. The study includes two assessments of cognitive function that were administered approximately 8 years apart. Objective: To test whether APOE genotype is associated with change of cognitive function in older adults. Methods: We used Bayesian hierarchical models to test the association between APOE alleles and change of cognitive function. Six longitudinally collected neuropsychological test scores were modelled as a function of age at enrollment, follow-up time, gender, education, field center, birth cohort indicator (≤1935, or >1935), and the number of copies of ɛ2 or ɛ4 alleles. Results: Out of 4,587 eligible participants, 2,064 were male (45.0%), and age at enrollment ranged from 25 to 110 years, with mean of 70.85 years (SD: 15.75). We detected a significant cross-sectional effect of the APOE ɛ4 allele on Logical Memory. Participants carrying at least one copy of the ɛ4 allele had lower scores in both immediate (–0.31 points, 95% CI: –0.57, –0.05) and delayed (–0.37 points, 95% CI: –0.64, –0.10) recall comparing to non-ɛ4 allele carriers. We did not detect any significant longitudinal effect of the ɛ4 allele. There was no cross-sectional or longitudinal effect of the ɛ2 allele. Conclusion: The APOE ɛ4 allele was identified as a risk factor for poorer episodic memory in older adults, while the APOE ɛ2 allele was not significantly associated with any of the cognitive test scores.

scholarly journals Genotypes and Phenotypes for Apolipoprotein E and Alzheimer Disease in the Honolulu-Asia Aging Study

2000 ◽  
Vol 46 (10) ◽  
pp. 1548-1554 ◽  
Author(s):  
Jan W P F Kardaun ◽  
Lon White ◽  
Helaine E Resnick ◽  
Helen Petrovitch ◽  
Santica M Marcovina ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Apolipoprotein E ◽  
Apoe Genotype ◽  
Population Based ◽  
Japanese American ◽  
Inverse Association ◽  
Population Based Study ◽  
Apoe Protein ◽  
Aging Study ◽  
Protein Isoform

Abstract Background: The utility of apolipoprotein E (ApoE) type as an indicator of genetic susceptibility to Alzheimer disease (AD) depends on the reliability of typing. Although ApoE protein isoform phenotyping is generally assumed equivalent to genotyping from DNA, phenotype-genotype differences have been reported. Methods: ApoE genotype and phenotype results were examined for 3564 older (ages 71–93 years) Japanese-American male participants of the Honolulu-Asia Aging Study, an ongoing population-based study of aging and dementia. Results: Both methods demonstrated similar associations of ApoE type with AD: a direct association with ApoE4 and a less dramatic inverse association ApoE2. Advanced age did not appear to influence the ApoE4-AD association. The association with AD among ApoE4 homozygotes [odds ratio (OR) = 14.7] was higher than expected based on an observed OR of 2.0 in heterozygotes. Phenotype-genotype nonconcordance was more frequent for ApoE2 than for ApoE4. The ApoE2 phenotype occurred at a frequency of 7.9% vs a genotype frequency of 4.9%, corresponding to a probability of 56% that an individual with ApoE2 phenotype had the same genotype. Conclusions: Whereas E4 and E2 phenotypes and genotypes were comparably associated with AD, neither method would be expected to substantially improve the efficiency of case finding in the context of population screening beyond prediction based on age and education. Nonconcordance of phenotype and genotype was substantial for E2 and modest for E4 in this population. The ApoE4-AD association was independent of age.

scholarly journals Cognitive trajectories from infancy to early adulthood following birth before 26 weeks of gestation: a prospective, population-based cohort study

2017 ◽  
Vol 103 (4) ◽  
pp. 363-370 ◽  
Author(s):  
Louise Linsell ◽  
Samantha Johnson ◽  
Dieter Wolke ◽  
Helen O’Reilly ◽  
Joan K Morris ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cognitive Function ◽  
Test Scores ◽  
Infant Development ◽  
Maternal Education ◽  
Early Adulthood ◽  
Population Based ◽  
Mean Difference ◽  
Cognitive Test ◽  
Extremely Preterm

ObjectiveTo determine the trajectory of cognitive test scores from infancy to adulthood in individuals born extremely preterm compared with term-born individuals.DesignA prospective, population-based cohort study.Setting276 maternity units in the UK and Ireland.Patients315 surviving infants born less than 26 completed weeks of gestation recruited at birth in 1995 and 160 term-born classroom controls recruited at age 6.Main outcome measuresBayley Scales of Infant Development-Second Edition (age 2.5); Kaufman Assessment Battery for Children (ages 6/11); Wechsler Abbreviated Scale of Intelligence-Second Edition (age 19).ResultsThe mean cognitive scores of extremely preterm individuals over the period were on average 25.2 points below their term-born peers (95% CI −27.8 to −22.6) and remained significantly lower at every assessment. Cognitive trajectories in term-born boys and girls did not differ significantly, but the scores of extremely preterm boys were on average 8.8 points below those of extremely preterm girls (95% CI −13.6 to −4.0). Higher maternal education elevated scores in both groups by 3.2 points (95% CI 0.8 to 5.7). Within the extremely preterm group, moderate/severe neonatal brain injury (mean difference: −10.9, 95% CI −15.5 to −6.3) and gestational age less than 25 weeks (mean difference: −4.4, 95% CI −8.4 to −0.4) also had an adverse impact on cognitive function.ConclusionsThere is no evidence that impaired cognitive function in extremely preterm individuals materially recovers or deteriorates from infancy through to 19 years. Cognitive test scores in infancy and early childhood reflect early adult outcomes.

The Relation Between p70S6k Expression in Lymphocytes and the Decline of Cognitive Test Scores in Patients With Alzheimer Disease

2005 ◽  
Vol 165 (20) ◽  
pp. 2428 ◽  
Author(s):  
Marc Paccalin ◽  
Stéphanie Pain-Barc ◽  
Claudette Pluchon ◽  
Chloé Paul ◽  
Hélène Bazin ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Test Scores ◽  
Cognitive Test
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