Distinct Cognitive Trajectories Research Articles

Distinct Cognitive Trajectories According to Amyloid Positivity in Non-Alzheimer Disease Dementias.

The clinical effects of β-amyloid positivity (Aβ+) on copathologies in various dementias remain relatively underexamined. Thus, the present study was conducted to investigate the prevalence and clinical effects of Aβ+ in subcortical vascular cognitive impairment (SVCI) and frontotemporal dementia (FTD). We enrolled SVCI (n = 583), FTD (n = 152), and cognitively unimpaired (CU) participants (n = 1,249) who underwent Aβ PET scans. The odds of having Aβ+ were subsequently compared among the diagnostic groups (CU, SVCI, and FTD) according to age and apolipoprotein E genotype. Additionally, a linear mixed-effects model was used to investigate the effects of Aβ+ on cognitive trajectories in SVCI and FTD. Compared with CU, the SVCI group had a higher prevalence of Aβ+ in the 75 to 90 years age group (adjusted odds ratio, 1.97; 95% confidence interval, 1.36-2.85; P < 0.001), as well as within the apolipoprotein E ε3/ε3 group (adjusted odds ratio, 1.78; 95% confidence interval, 1.20-2.63; P = 0.001), whereas the FTD group showed no difference in Aβ+ prevalence. Aβ+ was associated with a worse cognitive trajectory in SVCI (adjusted β-coefficient = -0.6424; P < 0.001), but not in FTD. These findings contribute to our understanding of Aβ biomarker traits in various dementias in Korea.

Association Between Cognitive Trajectories and Subsequent Health Status, Depressive Symptoms, and Mortality Among Older Adults in the United States: Findings From a Nationally Representative Study

Abstract Background Cognitive decline may be an early indicator of major health issues in older adults, though research using population-based data is lacking. Researchers objective was to assess the relationships between distinct cognitive trajectories and subsequent health outcomes, including health status, depressive symptoms, and mortality, using a nationally representative cohort. Methods Data were drawn from the National Health and Aging Trends Study. Global cognition was assessed annually between 2011 and 2018. The health status of 4 413 people, depressive symptoms in 4 342 individuals, and deaths among 5 955 living respondents were measured in 2019. Distinct cognitive trajectory groups were identified using an innovative Bayesian group-based trajectory model. Ordinal logistic, Poisson, and logistic regression models were used to examine the associations between cognitive trajectories and subsequent health outcomes. Results Researchers identified five cognitive trajectory groups with distinct baseline values and subsequent changes in cognitive function. Compared with the group with stably high cognitive function, worse cognitive trajectories (ie, lower baseline values and sharper declines) were associated with higher risks of poor health status, depressive symptoms, and mortality, even after adjusting for relevant covariates. Conclusions Among older adults, worse cognitive trajectories are strongly associated with subsequent poor health status, high depressive symptoms, and high mortality risks. Regular screening of cognitive function may help to facilitate early identification and interventions for older adults susceptible to adverse health outcomes.

Mental-somatic multimorbidity in trajectories of cognitive function for middle-aged and older adults.

Multimorbidity may confer higher risk for cognitive decline than any single constituent disease. This study aims to identify distinct trajectories of cognitive impairment probability among middle-aged and older adults, and to assess the effect of changes in mental-somatic multimorbidity on these distinct trajectories. Data from the Health and Retirement Study (1998-2016) were employed to estimate group-based trajectory models identifying distinct trajectories of cognitive impairment probability. Four time-varying mental-somatic multimorbidity combinations (somatic, stroke, depressive, stroke and depressive) were examined for their association with observed trajectories of cognitive impairment probability with age. Multinomial logistic regression analysis was conducted to quantify the association of sociodemographic and health-related factors with trajectory group membership. Respondents (N = 20,070) had a mean age of 61.0 years (SD = 8.7) at baseline. Three distinct cognitive trajectories were identified using group-based trajectory modelling: (1) Low risk with late-life increase (62.6%), (2) Low initial risk with rapid increase (25.7%), and (3) High risk (11.7%). For adults following along Low risk with late-life increase, the odds of cognitive impairment for stroke and depressive multimorbidity (OR:3.92, 95%CI:2.91,5.28) were nearly two times higher than either stroke multimorbidity (OR:2.06, 95%CI:1.75,2.43) or depressive multimorbidity (OR:2.03, 95%CI:1.71,2.41). The odds of cognitive impairment for stroke and depressive multimorbidity in Low initial risk with rapid increase or High risk (OR:4.31, 95%CI:3.50,5.31; OR:3.43, 95%CI:2.07,5.66, respectively) were moderately higher than stroke multimorbidity (OR:2.71, 95%CI:2.35, 3.13; OR: 3.23, 95%CI:2.16, 4.81, respectively). In the multinomial logistic regression model, non-Hispanic Black and Hispanic respondents had higher odds of being in Low initial risk with rapid increase and High risk relative to non-Hispanic White adults. These findings show that depressive and stroke multimorbidity combinations have the greatest association with rapid cognitive declines and their prevention may postpone these declines, especially in socially disadvantaged and minoritized groups.

Long-term characterization of cognitive phenotypes in children with seizures over 36 months

RationaleChildren with new-onset epilepsies often exhibit co-morbidities including cognitive dysfunction, which adversely affects academic performance. Application of unsupervised machine learning techniques has demonstrated the presence of discrete cognitive phenotypes at or near the time of diagnosis, but there is limited knowledge of their longitudinal trajectories. Here we investigate longitudinally the presence and progression of cognitive phenotypes and academic status in youth with new-onset seizures as sibling controls. Methods282 subjects (6–16 years) were recruited within 6 weeks of their first recognized seizure along with 167 unaffected siblings. Each child underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months later. Factor analysis of the neuropsychological tests revealed four underlying domains – language, processing speed, executive function, and verbal memory. Latent trajectory analysis of the mean factor scores over 36 months identified clusters with prototypical cognitive trajectories. ResultsThree unique phenotypic groups with distinct cognitive trajectories over the 36-month period were identified: Resilient, Average, and Impaired phenotypes. The Resilient phenotype exhibited the highest neuropsychological factor scores and academic performance that were all similar to controls; while the Impaired phenotype showed the polar opposite with the worst performances across all test metrics. These findings remained significant and stable over 36 months. Multivariate logistic regression indicated that age of onset, EEG, neurological examination, and sociodemographic disadvantage were associated with phenotype classification. ConclusionsThis study demonstrates the presence of diverse latent cognitive trajectory phenotypes over 36 months in youth with new-onset seizures that are associated with a stable neuropsychological and academic performance longitudinally.

Longitudinal brain changes in Parkinson's disease with severe olfactory deficit

IntroductionOlfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD. MethodsLongitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis. ResultsCompared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus. ConclusionsThe atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes.

Trajectories of Cognitive Function and Their Associated Factors in Community-Dwelling Older Adults by Living Arrangement Using the Korean Longitudinal Study of Aging

The purpose of this study was to describe the distinct cognitive trajectories for 8 years according to living arrangement among community-dwelling older adults using the Korean longitudinal study of ageing.We analyzed data from a final sample of 3,049 community-dwelling older adults aged 65 years or older who participated in at least three cognitive function measures in an 8-year period (2012-2020). Cognitive function was assessed by Korean mini mental state examination. Latent class growth model analysis was applied to determine the number and shape of trajectories of older adults according to living arrangement. Multinomial logistic regression analysis was used to determine risk factors for cognitive function trajectories.We identified five trajectory patterns in cognitive function among older adults living alone; ‘high-stable (35.6%)’, ‘high-declining (32.5%)’, ‘moderate-steep declining (6.2%)’, ‘low-stable (18.9%)’, and ‘low declining (6.8%)’. In older adults living with family, there were four trajectory patterns; ‘high-stable (46.4%)’, ‘high-declining (32.0%)’, ‘low-stable (15.9%)’, and ‘low-declining (5.7%)’. Age, instrumental activities of daily living, and depression were common factors of cognitive changes in both older adults living alone and those living with family members. However, monthly incomes was only associated with the risk of cognitive function in older adults living alone.We found that cognitive function trajectories among older adults may differ depending on the type of living arrangement. Therefore, further studies and health policies are required for avoiding cognitive impairment by living arrangement among older adults based on the results of this study.

Uncovering heterogeneous cognitive trajectories in mild cognitive impairment: a data-driven approach

BackgroundGiven the complex and progressive nature of mild cognitive impairment (MCI), the ability to delineate and understand the heterogeneous cognitive trajectories is crucial for developing personalized medicine and informing trial design. The primary goals of this study were to examine whether different cognitive trajectories can be identified within subjects with MCI and, if present, to characterize each trajectory in relation to changes in all major Alzheimer’s disease (AD) biomarkers over time.MethodsIndividuals with a diagnosis of MCI at the first visit and ≥ 1 follow-up cognitive assessment were selected from the Alzheimer’s Disease Neuroimaging Initiative database (n = 936; age 73 ± 8; 40% female; 16 ± 3 years of education; 50% APOE4 carriers). Based on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) total scores from baseline up to 5 years follow-up, a non-parametric k-means longitudinal clustering method was performed to obtain clusters of individuals with similar patterns of cognitive decline. We further conducted a series of linear mixed-effects models to study the associations of cluster membership with longitudinal changes in other cognitive measures, neurodegeneration, and in vivo AD pathologies.ResultsFour distinct cognitive trajectories emerged. Cluster 1 consisted of 255 individuals (27%) with a nearly non-existent rate of change in the ADAS-Cog-13 over 5 years of follow-up and a healthy-looking biomarker profile. Individuals in the cluster 2 (n = 336, 35%) and 3 (n = 240, 26%) groups showed relatively mild and moderate cognitive decline trajectories, respectively. Cluster 4, comprising about 11% of our study sample (n = 105), exhibited an aggressive cognitive decline trajectory and was characterized by a pronouncedly abnormal biomarker profile.ConclusionsIndividuals with MCI show substantial heterogeneity in cognitive decline. Our findings may potentially contribute to improved trial design and patient stratification.

Effects of cognitive ageing trajectories on multiple adverse outcomes among Chinese community-dwelling elderly population

BackgroundWhether cognitive ageing trajectory is related to common functional deficits independent of initial cognitive function remains inconclusive. We aimed to explore the adverse health effect and potential predictive factors of distinct cognitive trajectories among Chinese older adults.MethodsThree thousand five hundred eighty-one community-dwelling older adults who completed three consecutive cognitive function examinations with the Mini-Mental State Examination (MMSE) over 5 years and were without cognitive impairment at enrollment were included. A group-based trajectory model was used to estimate cognitive ageing trajectories. Multivariable-adjusted odds ratio (OR) and 95% confidence intervals (CI) were computed with logistic regression models to identify potential baseline determinants and health effect of cognitive trajectories on various adverse outcomes.ResultsTwo distinct cognitive ageing trajectories were identified with about 5.3% of the study participants ascribed to the rapidly decreasing group. Subjects with rapidly decreasing cognition showed significantly higher odds (OR, 95%CI) of experiencing frailty (4.04, 2.77–5.86), falls (2.01, 1.05–3.70), balance impairment (4.20, 2.75–6.38), high fall risk (5.66, 2.67–11.77) based on the Tinetti total score, disability in activities of daily living (1.76, 1.19–2.56), disability in instrumental activities of daily living (1.52, 1.05–2.19), and motor cognitive risk syndrome (2.24, 1.23–3.98) compared with their steadily decreasing counterparts. Individuals with older age, low education level, no marriage, high score of rapid eye movement behavior disorders, poor physical and cognitive function at baseline were more predisposed to an accelerated cognitive decline.ConclusionsFaster cognitive decline was independently associated with higher risk of multiple adverse events. Our findings put more emphasis on a routine and constant surveillance of cognitive function among community-dwelling older adults.

Potential modifiable factors associated with late-life cognitive trajectories.

ObjectiveThere is variability across individuals in cognitive aging. To investigate the associations of several modifiable factors with high and low cognitive performance.MethodsData came from 17,724 community-dwelling individuals aged 65–98 years. Global cognition, verbal fluency, episodic memory, and psychomotor speed were assessed over up to seven years. Group-based multi-trajectory modeling identified distinct cognitive trajectories. Structural equation modeling examined the direct/indirect associations of social/behavioral factors and several chronic conditions with cognitive trajectories.ResultsSeven trajectory subgroups were identified. In the structural equation modeling we compared two subgroups-participants with the highest (14.2%) and lowest (4.1%) cognitive performance with the average subgroup. Lower education, never alcohol intake, and frailty directly predicted increased risk of low performance, and decreased likelihood of high performance. Hypertension (RR: 0.69, 95%CI: 0.60–0.80), obesity (RR: 0.84, 95%CI: 0.73–0.97), diabetes (RR: 0.69, 95%CI: 0.56–0.86) and depression (RR: 0.68, 95%CI: 0.54–0.85) only predicted lower likelihood of high cognitive performance, while dyslipidemia was only associated with low performance (RR: 1.30, 95%CI: 1.07–1.57). Living alone predicted increased risk of low cognitive performance and several comorbidities. Smoking did not predict cognitive trajectories but was associated with increased risk of diabetes, obesity and frailty. Findings were similar when examining the direct associations between modifiable risk factors and all seven cognitive subgroups.ConclusionsAlthough several modifiable factors were associated with high performance, and reversely with low performance, this was not observed for obesity, hypertension and dyslipidemia. Further, health behaviors may affect cognitive function indirectly, via geriatric conditions. This indicates that strategies to promote healthy cognitive aging, may be distinct from those targeting dementia prevention.

Global cognitive trajectory patterns in Alzheimer's disease.

The literature on Alzheimer's disease (AD) provides little data about long-term cognitive course trajectories. We identify global cognitive outcome trajectories and associated predictor variables that may inform clinical research and care. Data derived from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set were used to examine the cognitive course of persons with possible or probable AD, a Mini-Mental State Examination (MMSE) of ≥10, and complete annual assessments for 5 years. Thirty-six Alzheimer's Disease Research Centers. Four hundred and fourteen persons. We used a hybrid approach comprising qualitative analysis of MMSE trajectory graphs that were operationalized empiricallyand binary logistic regression analyses to assess 19 variables' associations with each trajectory. MMSE scores of ±3 points or greater were considered clinically meaningful. Five distinct cognitive trajectories were identified: fast decliners (32.6%), slow decliners (30.7%), zigzag stable (15.9%), stable (15.9%), and improvers (4.8%). The decliner groups had three subtypes: curvilinear, zigzag, and late decline. The fast decliners were associated with female gender, lower baseline MMSE scores, a shorter illness duration, or receiving a cognitive enhancer. An early MMSE decline of ≥3 points predicted a worse outcome. A higher rate of traumatic brain injury, the absence of an ApoE ϵ4 allele, and male gender were the strongest predictors of favorable outcomes. Our hybrid approach revealed five distinct cognitive trajectories and a variegated pattern within the decliners and stable/improvers that was more consistent with real-world clinical experience than prior statistically modeled studies. Future investigations need to determine the consistency of the distribution of these categories across settings.

Trajectories of cognitive function and associated factors in community-dwelling older adults: a prospective study

There is variability in cognitive aging between individuals. This study aimed to investigate cognitive aging trajectories, the associated modifiable factors, and the association of these trajectories with dementia. Community-dwelling older adults (n=19,114) without dementia or major cognitive impairment at inclusion were followed for up to 7 years, with regular standardized cognitive assessments. Group-based (multi-) trajectory modeling identified distinct cognitive trajectories. Structural equation modeling (n=16,018) was used to analyze the associated predictors. Four to seven trajectories were identified per cognitive domain, with generally stable trajectories. Improvement in verbal fluency and minor psychomotor slowing were common. Substantial decline in global cognition and episodic memory were observed in a small proportion of individuals. The highest proportions of dementia cases were in trajectories with major decline in global cognition (56.9%) and memory (33.2%). A number of sociodemographic characteristics, health behaviors and chronic conditions were either directly or indirectly associated with cognitive change in older adults. This study found that some individuals appear resilient to cognitive decline even with advancing age, and that factors that promote healthy cognitive aging are not simply the absence of factors which confer risk for decline.

Trajectories of cognitive function in community-dwelling older adults: A longitudinal study of population heterogeneity.

IntroductionThis study aimed to investigate cognitive aging trajectories, the associated sociodemographic characteristics, and the association of these trajectories with dementia.MethodsGenerally healthy older adults (n = 19,114) were followed for up to 7 years, with regular cognitive assessments. Group‐based trajectory modeling identified distinct cognitive trajectories.ResultsFour to seven trajectories were identified per cognitive domain. Stable trajectories were observed across domains. Improvement in verbal fluency and minor psychomotor slowing were common. Substantial decline in global cognition and episodic memory were observed in a small proportion of individuals. Older, less educated participants and men were more common in lower‐functioning trajectories (p < .001). The highest proportions of dementia cases were in trajectories with major decline in global cognition (56.9%) and memory (33.2%).DiscussionInter‐individual variability in cognitive trajectories was observed across all domains. Some individuals appear resilient to cognitive decline even with advancing age. Further research into factors promoting cognitive resilience is needed.

Do I lose cognitive function as fast as my twin partner? Analyses based on classes of MMSE trajectories of twins aged 80 and older.

Aging is associated with an increasing risk of decline in cognitive abilities. The decline is, however, not a homogeneous process. There are substantial differences across individuals although previous investigations have identified individuals with distinct cognitive trajectories. Evidence is accumulating that lifestyle contributes significantly to the classification of individuals into various clusters. How and whether genetically related individuals, like twins, change in a more similar manner is yet not fully understood. In this study, we fitted growth mixture models to Mini Mental State Exam (MMSE) scores from participants of the Swedish OCTO twin study of oldest-old monozygotic and same-sex dizygotic twins with the purpose of investigating whether twin pairs can be assigned to the same class of cognitive change. We identified four distinct groups (latent classes) whose MMSE trajectories followed different patterns of change over time: two classes of high performing individuals who remained stable and declined slowly, respectively, a group of mildly impaired individuals with a fast decline and a small group of impaired individuals who declined more rapidly. Notably, our analyses show no association between zygosity and class assignment. Our study provides evidence for a more substantial impact of environmental, rather than genetic, influences on cognitive change trajectories in later life.

Distinct Cognitive Trajectories in Late Life and Associated Predictors and Outcomes: A Systematic Review.

Background:Cognitive aging is a dynamic process in late life with significant heterogeneity across individuals.Objective:To review the evidence for latent classes of cognitive trajectories and to identify the associated predictors and outcomes.Methods:A systematic search was performed in MEDLINE and EMBASE for articles that identified two or more cognitive trajectories in adults. The study was conducted following the PRISMA statement.Results:Thirty-seven studies were included, ranging from 219 to 9,704 participants, with a mean age of 60 to 93.4 years. Most studies (n = 30) identified distinct cognitive trajectories using latent class growth analysis. The trajectory profile commonly consisted of three to four classes with progressively decreasing baseline and increasing rate of decline—a ‘stable-high’ class characterized as maintenance of cognitive function at high level, a ‘minor-decline’ class or ‘stable-medium’ class that declines gradually over time, and a ‘rapid-decline’ class with the steepest downward slope. Generally, membership of better classes was predicted by younger age, being female, more years of education, better health, healthier lifestyle, higher social engagement and lack of genetic risk variants. Some factors (e.g., education) were found to be associated with cognitive function over time only within individual classes.Conclusion:Cognitive aging in late life is a dynamic process with significant inter-individual variability. However, it remains unclear whether similar patterns of cognitive aging are observed across all cognitive domains. Further research into unique factors which promote the maintenance of high-cognitive function is needed to help inform public policy.

PHENOTYPING PROSPECTIVE COGNITIVE OUTCOMES OF LATE-LIFE DEPRESSION

Introduction It has long been known that major depressive disorder during later life (LDD) is associated with cognitive decline and development of Alzheimer's disease and other dementias. Less is known about the characteristics of LLD that contribute to individual cognitive outcomes, but identifying phenotypes of these outcomes could make important contributions to early detection and treatment. The current study explored clinical and neuroimaging phenotypes associated with normal and non-normal cognitive diagnostic outcomes in LLD. Methods The data were from a prospective study of individuals (N = 240) with acute depression at baseline and followed under treatment for a minimum of five years. Baseline assessment included clinical measures of mood, neuropsychological assessment, and neuroimaging. Mood was assessed during regular treatment over the course of each year, and neuropsychological assessment was obtained annually. A consensus review was held annually to assign clinical diagnoses based on cognitive status, which included categories of normal cognition; cognitive impairment, no dementia (CIND); dementia, with subtypes including Alzheimer's disease (AD). The current study analyzed diagnostic outcomes at five years from study entry, and the clinical characteristics that predict these outcomes. Results We found that 90% of cognitive diagnostic outcomes over five-years of follow-up were in three diagnostic categories: 1) cognitively normal, 2) persistent CIND, and 3) AD. The remaining 10% were non-AD dementias and various medical and neuropsychiatric diagnoses. Individuals with normal cognition were 50% of the sample, and this endpoint was associated with first depression onset before age 60 and indicators of heightened sensitivity to stress. Individuals with persistent CIND (22%) were not associated with age of depression onset, but were associated with clinical characteristics of frailty and indicators of cerebrovascular pathology on neuroimaging. Individuals with AD (18%) were associated with age of depression onset after age 60, depressive symptoms of appetite/weight loss, reduced hippocampal volume, and worse memory performance at study entry. Conclusions The current study found distinct clinical and neuroimaging profiles associated with the three major cognitive endpoints of LLD. Approximately half of individuals with LLD maintained normal cognition over five years, which appeared to be associated with a lifetime predisposition to depression and heightened sensitivity to stress. In contrast, nearly 20% of individuals with LLD converted to AD within five years of follow up, and results suggest a clinically detectable phenotype of prodromal AD based on appetitive disturbance, reduced hippocampal volume, and memory deficits. Individuals with persistent CIND demonstrated a profile consistent with physical decline and cerebrovascular pathology, which did not manifest as dementia over 5 years, but may represent a slower progress toward vascular dementia relative to those with AD. These clinical phenotypes reflect a starting point for mechanistic discovery while also improving current treatment of LLD by identifying individuals on distinct cognitive trajectories who many benefit from differentiated approaches to the treatment of mood and cognition. The current cohort is part of a collaborative project to further detect and characterize linkages between cognitive outcomes of LLD and their clinical and neuroimaging phenotypes. This research was funded by This research was supported by funding from the National Institute of Mental Health (R01MH108560), and the Leo and Anne Albert Charitable Trust. The authors have no industry or other conflicts to report.

Distinct and heterogeneous trajectories of self‐perceived cognitive impairment among Asian breast cancer survivors

Currently, there are no studies that have established the self-perceived cognitive trajectories experienced by breast cancer patients (BCPs) post-chemotherapy. Therefore, we characterized the long-term trajectory of self-perceived cognitive function among Asian early-stage BCPs using the minimal clinically important difference of a subjective measure of cognitive function. Early-stage BCPs who received chemotherapy were recruited and assessed at 4 time points: Before chemotherapy initiation (T1), 6weeks post-chemotherapy initiation (T2), 12weeks post-chemotherapy initiation (T3), and 15-months post-chemotherapy initiation (T4). All assessments were performed approximately within 2weeks post-chemotherapy. Subjective and objective cognitive function were assessed using Functional Assessment of Cancer Therapy-Cognitive (version 3) and Headminder™. A total of 166 BCPs were recruited, of whom 131 completed assessment at all time points. Using the minimal clinically important difference of Functional Assessment of Cancer Therapy-Cognitive, 5 distinct cognitive trajectories were established. Of the 131 patients, 70 (53.4%) did not report any clinically significant cognitive impairment. Twenty-one (16.0%) patients reported acute cognitive changes during chemotherapy (T2 and/or T3) but not at T4. Forty patients (30.5%) reported clinically significant cognitive impairment at T4, of whom 18 did not report any cognitive impairment at earlier time points. Fifteen (11.5%) patients reported persistent cognitive impairment throughout all time points, while 7 (5.3%) patients reported intermittent cognitive impairment at T2 and T4 but not at T3. This is the first study to establish the existence of heterogeneous cognitive trajectories based on clinically significant thresholds of self-perceived cognitive impairment. The findings have important implications on the window for screening and management of post-chemotherapy cognitive impairment.

Distinct Cognitive Trajectories in the First Year After Hip Fracture.

Change in cognitive functioning is often observed after hip fracture. Different patterns, with both improvement and decline, are expected, depending on premorbid cognitive functioning and events that occur during hospitalization. These patterns are unknown and important for older hip fracture patients with different levels of premorbid cognitive functioning. We conducted a secondary analysis of a multi-center randomized controlled trial. 302 consecutive patients aged 65-102 years old, admitted for hip fracture surgery, were enrolled. The Mini Mental State Examination (MMSE) was obtained at hospital admission, at discharge, and at 3 and 12 months after discharge. Cognitive trajectories were identified with Group Based Trajectory Modelling, using the repeated MMSE measurements as outcome variable. To illustrate the specific characteristics of this relative novel methodological approach, it was contrasted with results obtained from linear mixed effects modeling. 146 (48.3%) patients had premorbid cognitive impairment and 85 patients (28.1%) experienced delirium during admission. Three distinct cognitive trajectories were identified and labeled based on different MMSE course over time: improvement (57.9%), stable (28.1%), and rapid decline (13.9%), with an annual MMSE change of 1.7, 0.8, and -3.5 points respectively. With mixed effects modeling an overall annual increase of 0.7 MMSE points was estimated for the group as a whole. Three distinct cognitive trajectories were identified in a population of older hip fracture patients. These trajectory groups can be used as a starting point to inform patients and caregivers on the possible prognosis after hip fracture. Group based trajectory modelling is a useful technique when the purpose is to describe patterns of change within a population and a variety of trajectories are expected to exist.

Cognitive Aging Trajectories and Burdens of Disability, Hospitalization and Nursing Home Admission Among Community-living Older Persons.

The course of cognitive aging has demonstrated substantial heterogeneity. This study attempted to identify distinctive cognitive trajectories and examine their relationship with burdens of disability, hospitalization, and nursing home admission. Seven hundred and fifty-four community-living persons aged 70 years or older in the Yale Precipitating Events Project were assessed with the Mini-Mental State Examination every 18 months for up to 108 months. A group-based trajectory model was used to determine cognitive aging trajectories while adjusting for age, sex, and education. Cumulative burden of disabilities, hospitalizations, and nursing home admissions over 141 months associated with the cognitive trajectories were evaluated using a generalized estimating equation Poisson model. Five distinct cognitive trajectories were identified, with about a third of participants starting with high baseline cognitive function and demonstrating No decline during the follow-up period. The remaining participants diverged with Minimal (prevalence 41%), Moderate (16%), Progressive (8%), and Rapid (3%) cognitive decline. Participants with No decline incurred the lowest incidence rates (per 1,000 person-months) of disability in activities of daily living (ADL; 75, 95% confidence intervals: 60-95) and instrumental ADL (492, 453-535), hospitalization (29, 26-33) and nursing home admission (18, 12-27), whereas participants on the Rapid trajectory experienced the greatest burden of ADL disability (612, 595-758) and those on the Progressive trajectory had the highest nursing home admission (363, 292-451). Community-living older persons follow distinct cognitive aging trajectories and experience increasing burdens of disability, hospitalization, and nursing home placement as they age, with greater burdens for those on a declining cognitive trajectory.

Residual decline in cognition after adjustment for common neuropathologic conditions.

Neurodegenerative and cerebrovascular conditions are common in old age and are associated with cognitive decline. However, considerable heterogeneity remains in residual decline (i.e., person-specific trajectories of cognitive decline adjusted for these common neuropathologic conditions). The present study aimed to characterize profiles of residual decline in late life cognition. Up to 19 waves of longitudinal cognitive data were collected from 876 autopsied participants from 2 ongoing clinical-pathologic cohort studies of aging. Uniform neuropathologic examinations quantified measures of Alzheimer's disease, cerebral infarcts, Lewy body disease, and hippocampal sclerosis. Random effects mixture models characterized latent profiles of residual decline in global cognition. We identified 4 latent groups, and each group demonstrated distinct residual decline profiles. On average, 44% of the participants had little or no decline, 35% showed moderate decline, 13% showed severe decline and the rest (8%) had substantial within-subject fluctuation of longitudinal cognitive measures. These latent groups differed in psychological, experiential and neurobiologic factors that have been previously shown to be associated with cognitive decline. Specifically, compared with nondecliners, decliners had more depressive symptoms, were more socially isolated; were less engaged in cognitive or physical activities; and had lower density of noradrenergic neurons in locus ceruleus. After controlling for common dementia related pathologies, considerable residual variability remains in cognitive aging trajectories and this variability is not random but rather is related to markers of cognitive and neural reserve. The mixture modeling approach provides a powerful tool to identify latent groups with distinct cognitive trajectories.

Editorial: Capturing Developmental Trajectories of Change in Persons With Intellectual and Developmental Disability

Editorial: Capturing Developmental Trajectories of Change in Persons With Intellectual and Developmental Disability