Dataset Information

Decline in cognitively complex everyday activities accelerates along the Alzheimer's disease continuum.

ABSTRACT:

Background

Impairment in daily functioning is a clinical hallmark of dementia. Difficulties with "instrumental activities of daily living" (IADL) seem to increase gradually over the course of Alzheimer's disease (AD), before dementia onset. However, it is currently not well established how difficulties develop along the preclinical and prodromal stages of AD. We aimed to investigate the trajectories of decline in IADL performance, as reported by a study partner, along the early stages of AD.

Methods

In a longitudinal multicenter study, combining data from community-based and memory clinic cohorts, we included 1555 individuals (mean age 72.5 ± 7.8 years; 50% female) based on availability of amyloid biomarkers, longitudinal IADL data, and clinical information at baseline. Median follow-up duration was 2.1 years. All amyloid-positive participants (n = 982) were classified into the National Institute on Aging-Alzheimer's Association (NIA-AA) clinical stages ranging from preclinical AD (1) to overt dementia (4+). Cognitively normal amyloid-negative individuals (n = 573) served as a comparison group. The total scores of three study-partner reported IADL questionnaires were standardized.

Results

The rate of decline in cognitively normal (stage 1) individuals with and without abnormal amyloid did not differ (p = .453). However, from stage 2 onwards, decline was significantly faster in individuals on the AD continuum (B [95%CI] = - 0.32 [- 0.55, - 0.09], p = .007). The rate of decline increased with each successive stage: one standard deviation (SD) unit per year in stage 3 (- 1.06 [- 1.27, - 0.85], p < .001) and nearly two SD units per year in stage 4+ (1.93 [- 2.19, - 1.67], p < .001). Overall, results were similar between community-based and memory clinic study cohorts.

Conclusions

Our results suggest that the rate of functional decline accelerates along the AD continuum, as shown by steeper rates of decline in each successive NIA-AA clinical stage. These results imply that incremental changes in function are a meaningful measure for early disease monitoring. Combined with the low-cost assessment, this advocates the use of these functional questionnaires for capturing the effects of early AD-related cognitive decline on daily life.

SUBMITTER: Dubbelman MA

PROVIDER: S-EPMC7597034 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Decline in cognitively complex everyday activities accelerates along the Alzheimer's disease continuum.

Dubbelman Mark A MA Jutten Roos J RJ Tomaszewski Farias Sarah E SE Amariglio Rebecca E RE Buckley Rachel F RF Visser Pieter Jelle PJ Rentz Dorene M DM Johnson Keith A KA Properzi Michael J MJ Schultz Aaron A Donovan Nancy N Gatchell Jennifer R JR Teunissen Charlotte E CE Van Berckel Bart N M BNM Van der Flier Wiesje M WM Sperling Reisa A RA Papp Kathryn V KV Scheltens Philip P Marshall Gad A GA Sikkes Sietske A M SAM

Alzheimer's research & therapy 20201029 1

<h4>Background</h4>Impairment in daily functioning is a clinical hallmark of dementia. Difficulties with "instrumental activities of daily living" (IADL) seem to increase gradually over the course of Alzheimer's disease (AD), before dementia onset. However, it is currently not well established how difficulties develop along the preclinical and prodromal stages of AD. We aimed to investigate the trajectories of decline in IADL performance, as reported by a study partner, along the early stages of ...[more]

PMID: 33121534

Similar Datasets

Project description:BackgroundNeuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer's disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD continuum, to reveal putative protective or harmful stage-dependent patterns of activation.MethodsWe included healthy controls (n = 36) and Aβ-positive (Aβ+) cases (as defined by pathological CSF amyloid beta 1-42 (Aβ42)) with either subjective cognitive decline (SCD, n = 19), mild cognitive impairment (MCI, n = 39), or AD dementia (n = 27). The following CSF markers were measured: a microglial activation marker-soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a marker of microglial inflammatory reaction-monocyte chemoattractant protein-1 (MCP-1), two astroglial activation markers-chitinase-3-like protein 1 (YKL-40) and clusterin, a neuron-microglia communication marker-fractalkine, and the CSF AD biomarkers (Aβ42, phosphorylated tau (P-tau), total tau (T-tau)). Using ANOVA with planned comparisons, or Kruskal-Wallis tests with Dunn's pairwise comparisons, CSF levels were compared between clinical groups and between stages of biomarker severity using CSF biomarkers for classification based on amyloid pathology (A), tau pathology (T), and neurodegeneration (N) giving rise to the A/T/N score.ResultsCompared to healthy controls, sTREM2 was increased in SCD (p < .01), MCI (p < .05), and AD dementia cases (p < .001) and increased in AD dementia compared to MCI cases (p < .05). MCP-1 was increased in MCI (p < .05) and AD dementia compared to both healthy controls (p < .001) and SCD cases (p < .01). YKL-40 was increased in dementia compared to healthy controls (p < .01) and MCI (p < .05). All of the CSF activation markers were increased in subjects with pathological CSF T-tau (A+T-N+ and A+T+N+), compared to subjects without neurodegeneration (A-T-N- and A+T-N-).DiscussionMicroglial activation as indicated by increased sTREM2 is present already at the preclinical SCD stage; increased MCP-1 and astroglial activation markers (YKL-40 and clusterin) were noted only at the MCI and AD dementia stages, respectively, and in Aβ+ cases (A+) with pathological T-tau (N+). Possible different effects of early and later glial activation need to be explored.

Project description:Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer's disease dementia and mild cognitive impairment. However, it is still unknown whether these alterations can be found in individuals with subjective cognitive decline, and whether they are more pronounced than changes found in conventional brain volumetric measurements. To address these questions, we investigated microstructural alterations of two major cholinergic pathways in individuals along the Alzheimer's disease continuum using an in vivo model of the human cholinergic system based on neuroimaging. We included 402 participants (52 Alzheimer's disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study. We modelled the cholinergic white matter pathways with an enhanced diffusion neuroimaging pipeline that included probabilistic fibre-tracking methods and prior anatomical knowledge. The integrity of the cholinergic white matter pathways was compared between stages of the Alzheimer's disease continuum, in the whole cohort and in a CSF amyloid-beta stratified subsample. The discriminative power of the integrity of the pathways was compared to the conventional volumetric measures of hippocampus and nucleus basalis of Meynert, using a receiver operating characteristics analysis. A multivariate model was used to investigate the role of these pathways in relation to cognitive performance. We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer's disease continuum, including individuals with subjective cognitive decline. The differences involved posterior cholinergic white matter in the subjective cognitive decline stage and extended to anterior frontal white matter in mild cognitive impairment and Alzheimer's disease dementia stages. Both cholinergic pathways and conventional volumetric measures showed higher predictive power in the more advanced stages of the disease, i.e. mild cognitive impairment and Alzheimer's disease dementia. In contrast, the integrity of cholinergic pathways was more informative in distinguishing subjective cognitive decline from healthy controls, as compared with the volumetric measures. The multivariate model revealed a moderate contribution of the cholinergic white matter pathways but not of volumetric measures towards memory tests in the subjective cognitive decline and mild cognitive impairment stages. In conclusion, we demonstrated that cholinergic white matter pathways are altered already in subjective cognitive decline individuals, preceding the more widespread alterations found in mild cognitive impairment and Alzheimer's disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer's disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert.

Project description:IntroductionTraditional multivariate methods for neuroimaging studies overlook the interdependent relationship between brain features. This study addresses this gap by analyzing relative brain volumetric patterns to capture how Alzheimer's disease (AD) and genetics influence brain structure along the disease continuum.MethodsThis study analyzed data from participants across the AD continuum from the Alzheimer's and Families (ALFA) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. Compositional data analysis (CoDA) was exploited to examine relative brain volumetric variations that (1) were linked to different AD stages compared to cognitively unimpaired amyloid-β-negative (CU A-) individuals and (2) varied by AD genetic risk.ResultsDisease stage-specific compositional brain scores were identified, differentiating CU A- individuals from those in more advanced stages. Genetic risk-stratified models revealed a broader genetic landscape affecting brain morphology in AD, beyond the well-known apolipoprotein E ε4 allele.DiscussionCoDA emerges as an alternative multivariate framework to deepen understanding of AD-related structural changes and support targeted interventions for those at higher genetic risk.HighlightsCompositional data analysis (CoDA) revealed the relative variation of brain region volumes, captured in compositional brain scores, capable of discerning between cognitively unimpaired amyloid-β-negative individuals and subjects within other disease-stage groups along the Alzheimer's disease (AD) continuum. CoDA also uncovered the genetic vulnerability of specific brain regions at each stage of the disease along the continuum. CoDA is capable of integrating magnetic resonance imaging data from two different cohorts without stringent requirements for harmonization. This translates as an advantage, compared to traditional methods, and strengthens the reliability of cross-study comparisons by standardizing the data despite different labeling agreements, facilitating collaborative and large-scale research. The algorithm is sensitive to AD-specific effects, as the main compositional brain scores display little overlap with the age-specific compositional brain score. CoDA provides a more accurate analysis of brain imaging data addressing its compositional nature, which can influence the development of targeted approaches, opening new avenues for enhancing brain health.

Dataset Information

Decline in cognitively complex everyday activities accelerates along the Alzheimer's disease continuum.

Background

Methods

Results

Conclusions

Publications

Decline in cognitively complex everyday activities accelerates along the Alzheimer's disease continuum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets