Cognitive activity relates to cognitive performance but not to Alzheimer disease biomarkers.
Ontology highlight
ABSTRACT: Objective
We aimed to determine whether there was a relationship between lifestyle factors and Alzheimer disease biomarkers.Methods
In a cross-sectional study, we evaluated self-reported histories of recent and past cognitive activity, self-reported history of recent physical activity, and objective recent walking activity in 186 clinically normal individuals with mean age of 74 ± 6 years. Using backward elimination general linear models, we tested the hypotheses that greater cognitive or physical activity would be associated with lower Pittsburgh compound B-PET retention, greater (18)F-fluorodeoxyglucose-PET metabolism, and larger hippocampal volume, as well as better cognitive performance on neuropsychological testing.Results
Linear regression demonstrated that history of greater cognitive activity was correlated with greater estimated IQ and education, as well as better neuropsychological testing performance. Self-reported recent physical activity was related to objective exercise monitoring. However, contrary to hypotheses, we did not find evidence of an association of Pittsburgh compound B retention, (18)F-fluorodeoxyglucose uptake, or hippocampal volume with past or current levels of cognitive activity, or with current physical activity.Conclusions
We conclude that a history of lifelong cognitive activity may support better cognitive performance by a mechanism that is independent of brain β-amyloid burden, brain glucose metabolism, or hippocampal volume.
SUBMITTER: Gidicsin CM
PROVIDER: S-EPMC4501938 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveTo test the hypothesis that frequent cognitive activity predicts slower cognitive decline before dementia onset in Alzheimer disease (AD) and faster decline thereafter.MethodsAs part of a longitudinal cohort study, older residents of a geographically defined population were assessed at 3-year intervals with brief cognitive performance tests from which a composite measure of global cognition was derived. After each wave of testing, a subset was sampled for clinical evaluation. The present analyses are based on 1,157 participants. They were free of dementia at study enrollment at which time they rated frequency of participation in common cognitively stimulating activities from which a previously validated summary measure was derived. They were sampled for clinical evaluation a mean of 5.6 years after enrollment and subsequently followed a mean of 5.7 years with brief cognitive performance testing at 3-year intervals.ResultsOn clinical evaluation, 614 people had no cognitive impairment, 395 had mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of global cognitive decline in persons without cognitive impairment was reduced by 52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the cognitive activity scale. In the mild cognitive impairment group, cognitive decline rate was unrelated to cognitive activity (estimate = -0.019, SE = 0.018, p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate = 0.075, SE = 0.021, p < 0.001) for each point on the cognitive activity scale.ConclusionMentally stimulating activity in old age appears to compress the cognitive morbidity associated with AD by slowing cognitive decline before dementia onset and hastening it thereafter.
| S-EPMC2942032 | biostudies-literature
Project description:Core CSF changes in Alzheimer disease (AD) are decreased amyloid ?(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly.We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis.The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages.Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations.
| S-EPMC3280049 | biostudies-literature
Project description:ImportanceAlzheimer disease (AD) pathology starts with a prolonged phase of β-amyloid (Aβ) accumulation without symptoms. The duration of this phase differs greatly among individuals. While this disease phase has high relevance for clinical trial designs, it is currently unclear how to best predict the onset of clinical progression.ObjectiveTo evaluate combinations of different plasma biomarkers for predicting cognitive decline in Aβ-positive cognitively unimpaired (CU) individuals.Design, setting, and participantsThis prospective population-based prognostic study evaluated data from 2 prospective longitudinal cohort studies (the Swedish BioFINDER-1 and the Wisconsin Registry for Alzheimer Prevention [WRAP]), with data collected from February 8, 2010, to October 21, 2020, for the BioFINDER-1 cohort and from August 11, 2011, to June 27, 2021, for the WRAP cohort. Participants were CU individuals recruited from memory clinics who had brain Aβ pathology defined by cerebrospinal fluid (CSF) Aβ42/40 in the BioFINDER-1 study and by Pittsburgh Compound B (PiB) positron emission tomography (PET) in the WRAP study. A total of 564 eligible Aβ-positive and Aβ-negative CU participants with available relevant data from the BioFINDER-1 and WRAP cohorts were included in the study; of those, 171 Aβ-positive participants were included in the main analyses.ExposuresBaseline P-tau181, P-tau217, P-tau231, glial fibrillary filament protein, and neurofilament light measured in plasma; CSF biomarkers in the BioFINDER-1 cohort, and PiB PET uptake in the WRAP cohort.Main outcomes and measuresThe primary outcome was longitudinal measures of cognition (using the Mini-Mental State Examination [MMSE] and the modified Preclinical Alzheimer Cognitive Composite [mPACC]) over a median of 6 years (range, 2-10 years). The secondary outcome was conversion to AD dementia. Baseline biomarkers were used in linear regression models to predict rates of longitudinal cognitive change (calculated separately). Models were adjusted for age, sex, years of education, apolipoprotein E ε4 allele status, and baseline cognition. Multivariable models were compared based on model R2 coefficients and corrected Akaike information criterion.ResultsAmong 171 Aβ-positive CU participants included in the main analyses, 119 (mean [SD] age, 73.0 [5.4] years; 60.5% female) were from the BioFINDER-1 study, and 52 (mean [SD] age, 64.4 [4.6] years; 65.4% female) were from the WRAP study. In the BioFINDER-1 cohort, plasma P-tau217 was the best marker to predict cognitive decline in the mPACC (model R2 = 0.41) and the MMSE (model R2 = 0.34) and was superior to the covariates-only models (mPACC: R2 = 0.23; MMSE: R2 = 0.04; P < .001 for both comparisons). Results were validated in the WRAP cohort; for example, plasma P-tau217 was associated with mPACC slopes (R2 = 0.13 vs 0.01 in the covariates-only model; P = .01) and MMSE slopes (R2 = 0.29 vs 0.24 in the covariates-only model; P = .046). Sparse models were identified with plasma P-tau217 as a predictor of cognitive decline. Power calculations for enrichment in hypothetical clinical trials revealed large relative reductions in sample sizes when using plasma P-tau217 to enrich for CU individuals likely to experience cognitive decline over time.Conclusions and relevanceIn this study, plasma P-tau217 predicted cognitive decline in patients with preclinical AD. These findings suggest that plasma P-tau217 may be used as a complement to CSF or PET for participant selection in clinical trials of novel disease-modifying treatments.
| S-EPMC10087054 | biostudies-literature
Project description:IntroductionAssociations of physical exercise with Alzheimer disease (AD) biomarkers and cognitive functioning have been observed cross-sectionally. However, the effects of exercise on longitudinal change in AD biomarkers have not been thoroughly investigated. The current study examined whether individuals with higher baseline exercise exhibited less longitudinal change in AD biomarkers and cognitive functioning, and whether APOE and/or brain-derived neurotrophic factor (BDNF) genotypes moderated the effects of exercise on longitudinal changes.MethodsClinically normal individuals completed a questionnaire on physical exercise over the prior 10-year period at baseline. Ninety-five individuals had serial cerebrospinal fluid samples collected to examine Aβ42, ptau181 and total tau; 181 individuals underwent multiple assessments of amyloid positron emission tomography imaging with Pittsburgh Compound-B; 327 individuals underwent multiple cognitive assessments, including measures of episodic memory, executive functions, verbal fluency, and processing speed.ResultsGreater exercise was associated with less steep decline in processing speed. Baseline exercise did not robustly impact longitudinal change for any other outcomes. Neither APOE nor BDNF genotype robustly moderated the effect of exercise on trajectories of AD biomarkers or cognitive decline.InterpretationResults suggest that self-reported physical exercise may be limited as a moderator of changes in AD biomarkers.
| S-EPMC7483844 | biostudies-literature
Project description:To test whether CSF Alzheimer disease biomarkers (?-amyloid 42 [A?42], tau, phosphorylated tau at threonine 181 [ptau181], tau/A?42, and ptau181/A?42) predict future decline in noncognitive outcomes among individuals cognitively normal at baseline.Longitudinal data from participants (N = 430) who donated CSF within 1 year of a clinical assessment indicating normal cognition and were aged 50 years or older were analyzed. Mixed linear models were used to test whether baseline biomarker values predicted future decline in function (instrumental activities of daily living), weight, behavior, and mood. Clinical Dementia Rating Sum of Boxes and Mini-Mental State Examination scores were also examined.Abnormal levels of each biomarker were related to greater impairment with time in behavior (p < 0.035) and mood (p < 0.012) symptoms, and more difficulties with independent activities of daily living (p < 0.012). However, biomarker levels were unrelated to weight change with time (p > 0.115). As expected, abnormal biomarker values also predicted more rapidly changing Mini-Mental State Examination (p < 0.041) and Clinical Dementia Rating Sum of Boxes (p < 0.001) scores compared with normal values.CSF biomarkers among cognitively normal individuals are associated with future decline in some, but not all, noncognitive Alzheimer disease symptoms studied. Additional work is needed to determine the extent to which these findings generalize to other samples.
| S-EPMC3854826 | biostudies-other
Project description:ObjectiveRecent studies suggest that white matter hyperintensities (WMH) on MRI, which primarily reflect small vessel cerebrovascular disease, may play a role in the evolution of Alzheimer disease (AD). In a longitudinal study, we investigated whether WMH promote the progression of AD pathology, or alter the association between AD pathology and risk of progression from normal cognition to mild cognitive impairment (MCI).MethodsTwo sets of analyses were conducted. The relationship between whole brain WMH load, based on fluid-attenuated inversion recovery MRI, obtained in initially cognitively normal participants (n = 274) and time to onset of symptoms of MCI (n = 60) was examined using Cox regression models. In a subset of the participants with both MRI and CSF data (n = 204), the interaction of WMH load and CSF AD biomarkers was also evaluated.ResultsBaseline WMH load interacted with CSF total tau (t-tau) with respect to symptom onset, but not with CSF β-amyloid 1-42 or phosphorylated tau (p-tau) 181. WMH volume was associated with time to symptom onset of MCI among individuals with low t-tau (hazard ratio [HR] 1.35, confidence interval [CI] 1.06-1.73, p = 0.013), but not those with high t-tau (HR 0.86, CI 0.56-1.32, p = 0.47). The rate of change in the CSF biomarkers over time was not associated with the rate of change in WMH volumes.ConclusionThese results suggest that WMH primarily affect the risk of progression when CSF measures of neurodegeneration or neuronal injury (as reflected by t-tau) are low. However, CSF biomarkers of amyloid and p-tau and WMH appear to have largely independent and nonsynergistic effects on the risk of progression to MCI.
| S-EPMC7238945 | biostudies-literature
Project description:To empirically assess the concept that Alzheimer disease (AD) biomarkers significantly depart from normality in a temporally ordered manner.Validation sample.Multisite, referral centers.A total of 401 elderly participants in the Alzheimer's Disease Neuroimaging Initiative who were cognitively normal, who had mild cognitive impairment, or who had AD dementia. We compared the proportions of 3 AD biomarker values (the A?42 level in cerebrospinal fluid [CSF], the total tau level in CSF, and the hippocampal volume adjusted for intracranial volume [hereafter referred to as the adjusted hippocampal volume]) that were abnormal as cognitive impairment worsened. Cut points demarcating normal vs abnormal for each biomarker were established by maximizing diagnostic accuracy in independent autopsy samples.Three AD biomarkers (ie, the CSF A?42 level, the CSF total tau level, and the adjusted hippocampal volume).Within each clinical group of the entire sample (n = 401), the CSF A?42 level was abnormal more often than was the CSF total tau level or the adjusted hippocampal volume. Among the 298 participants with both baseline and 12-month data, the proportion of participants with an abnormal A?42 level did not change from baseline to 12 months in any group. The proportion of participants with an abnormal total tau level increased from baseline to 12 months in cognitively normal participants (P = .05) but not in participants with mild cognitive impairment or AD dementia. For 209 participants with an abnormal CSF A?42 level at baseline, the percentage with an abnormal adjusted hippocampal volume but normal CSF total tau level increased from baseline to 12 months in participants with mild cognitive impairment. No change in the percentage of MCI participants with an abnormal total tau level was seen between baseline and 12 months.A reduction in the CSF A?42 level denotes a pathophysiological process that significantly departs from normality (ie, becomes dynamic) early, whereas the CSF total tau level and the adjusted hippocampal volume are biomarkers of downstream pathophysiological processes. The CSF total tau level becomes dynamic before the adjusted hippocampal volume, but the hippocampal volume is more dynamic in the clinically symptomatic mild cognitive impairment and AD dementia phases of the disease than is the CSF total tau level.
| S-EPMC3387980 | biostudies-literature
Project description:ImportanceIdentifying the youngest age when Alzheimer disease (AD) influences cognition and the earliest affected cognitive domains will improve understanding of the natural history of AD and approaches to early diagnosis.ObjectiveTo evaluate the age at which cognitive differences between individuals with higher compared with lower genetic risk of AD are first apparent and which cognitive assessments show the earliest difference.Design, setting, and participantsThis cross-sectional study used data from UK Biobank participants of European genetic ancestry, aged 40 years or older, who contributed genotypic and cognitive test data from January 1, 2006, to December 31, 2015. Data analysis was performed from March 10, 2020, to January 4, 2022.ExposureThe AD genetic risk score (GRS), which is a weighted sum of 23 single-nucleotide variations.Main outcomes and measuresSeven cognitive tests were administered via touchscreen at in-person visits or online. Cognitive domains assessed included fluid intelligence, episodic memory, processing speed, executive functioning, and prospective memory. Multiple cognitive measures were derived from some tests, yielding 32 separate measures. Interactions between age and AD-GRS for each of the 32 cognitive measures were tested with linear regression using a Bonferroni-corrected P value threshold. For cognitive measures with significant evidence of age by AD-GRS interaction, the youngest age of interaction was assessed with new regression models, with nonlinear specification of age terms. Models with youngest age of interaction from 40 to 70 years, in 1-year increments, were compared, and the best-fitting model for each cognitive measure was chosen. Results across cognitive measures were compared to determine which cognitive indicators showed earliest AD-related change.ResultsA total of 405 050 participants (mean [SD] age, 57.1 [7.9] years; 54.1% female) were included. Sample sizes differed across cognitive tests (from 12 455 to 404 682 participants). The AD-GRS significantly modified the association with age on 13 measures derived from the pairs matching (range in difference in mean cognition per decade increase in age for 1-SD higher AD-GRS, 2.5%-11.5%), symbol digit substitution (range in difference in mean cognition per decade increase in age for 1-SD higher AD-GRS, 2.0%-5.8%), and numeric memory tests (difference in mean cognition per decade increase in age for 1-SD higher AD-GRS, 8.8%) (P = 1.56 × 10-3). Best-fitting models suggested that cognitive scores of individuals with a high vs low AD-GRS began to diverge by 56 years of age for all 13 measures and by 47 years of age for 9 measures.Conclusions and relevanceIn this cross-sectional study, by early midlife, subtle differences in memory and attention were detectable among individuals with higher genetic risk of AD.
| S-EPMC8980909 | biostudies-literature
Project description:BackgroundCerebrospinal fluid (CSF) microRNA (miRNA) biomarkers of Alzheimer's disease (AD) have been identified, but have not been evaluated in prodromal AD, including mild cognitive impairment (MCI).ObjectiveTo assess whether a set of validated AD miRNA biomarkers in CSF are also sensitive to early-stage pathology as exemplified by MCI diagnosis.MethodsWe measured the expression of 17 miRNA biomarkers for AD in CSF samples from AD, MCI, and cognitively normal controls (NC). We then examined classification performance of the miRNAs individually and in combination. For each miRNA, we assessed median expression in each diagnostic group and classified markers as trending linearly, nonlinearly, or lacking any trend across the three groups. For trending miRNAs, we assessed multimarker classification performance alone and in combination with apolipoprotein E ɛ4 allele (APOEɛ4) genotype and amyloid-β42 to total tau ratio (Aβ42:T-Tau). We identified predicted targets of trending miRNAs using pathway analysis.ResultsFive miRNAs showed a linear trend of decreasing median expression across the ordered diagnoses (control to MCI to AD). The trending miRNAs jointly predicted AD with area under the curve (AUC) of 0.770, and MCI with AUC of 0.705. Aβ42:T-Tau alone predicted MCI with AUC of 0.758 and the AUC improved to 0.813 (p = 0.051) after adding the trending miRNAs. Multivariate correlation of the five trending miRNAs with Aβ42:T-Tau was weak.ConclusionSelected miRNAs combined with Aβ42:T-Tau improved classification performance (relative to protein biomarkers alone) for MCI, despite a weak correlation with Aβ42:T-Tau. Together these data suggest that that these miRNAs carry novel information relevant to AD, even at the MCI stage. Preliminary target prediction analysis suggests novel roles for these biomarkers.
| S-EPMC9262405 | biostudies-literature
Project description:Alzheimer's disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition. fMRI studies of the human connectome have recently reported that AD patients present diminished functional efficiency in resting-state networks, leading to a loss in information flow and cognitive processing. No study has investigated, however, whether CR modifies the effects of the pathology in functional network efficiency in AD patients. We analyzed the relationship between CR, pathophysiology and network efficiency, and whether CR modifies the relationship between them. Fourteen mild AD, 28 amnestic mild cognitive impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and graph metrics to measure network efficiency. We found no relationship between CR and CSF biomarkers; CR was related to higher network efficiency in all groups; and abnormal levels of CSF protein biomarkers were related to more efficient networks in the AD group. Education modified the effects of tau-related pathology in the aMCI and mild AD groups. Although higher CR might not protect individuals from developing AD pathophysiology, AD patients with higher CR are better able to cope with the effects of pathology-presenting more efficient networks despite pathology burden. The present study highlights that interventions focusing on cognitive stimulation might be useful to slow age-related cognitive decline or dementia and lengthen healthy aging.
| S-EPMC6111617 | biostudies-literature