The trajectory of cognitive decline in the pre-dementia phase in memory clinic visitors: findings from the 4C-MCI study

Hamel, Renske; Köhler, Sebastian; Sistermans, Nicole; Koene, Teddy; Pijnenburg, Y.A.L.; Flier, Wiesje M. van der; Scheltens, Philip; Aalten, Pauline; Verhey, Frans R.J.; Visser, Pieter Jelle; Ramakers, Inez H.G.B.

doi:10.1017/s0033291714002645

Cited by 45 publications

(33 citation statements)

References 52 publications

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“…One key purpose of clinical assessment is to be able to predict the temporal path of AD at the individual level; for example, if and when MCI due to AD or prodromal AD will progress to AD dementia. Impairment in episodic memory (i.e., the ability to learn and retain new information) is seen most commonly in individuals who subsequently progress to a diagnosis of AD dementia [ 42 , 54 ]. Based on this, tools that assess episodic memory, both immediate and delayed recall, are valuable.…”

Section: Role Of Clinical Assessmentmentioning

confidence: 99%

On the path to 2025: understanding the Alzheimer’s disease continuum

et al. 2017

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Basic research advances in recent years have furthered our understanding of the natural history of Alzheimer’s disease (AD). It is now recognized that pathophysiological changes begin many years prior to clinical manifestations of disease and the spectrum of AD spans from clinically asymptomatic to severely impaired. Defining AD purely by its clinical presentation is thus artificial and efforts have been made to recognize the disease based on both clinical and biomarker findings. Advances with biomarkers have also prompted a shift in how the disease is considered as a clinico-pathophysiological entity, with an increasing appreciation that AD should not only be viewed with discrete and defined clinical stages, but as a multifaceted process moving along a seamless continuum. Acknowledging this concept is critical to understanding the development process for disease-modifying therapies, and for initiating effective diagnostic and disease management options. In this article, we discuss the concept of a disease continuum from pathophysiological, biomarker, and clinical perspectives, and highlight the importance of considering AD as a continuum rather than discrete stages. While the pathophysiology of AD has still not been elucidated completely, there is ample evidence to support researchers and clinicians embracing the view of a disease continuum in their study, diagnosis, and management of the disease.

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Section: Role Of Clinical Assessmentmentioning

confidence: 99%

On the path to 2025: understanding the Alzheimer’s disease continuum

et al. 2017

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“…For example, global cognition usually declines slower than specific cognitive domains because older adults can compensate for global cognitive loss via multiple factors [17-19]. Moreover, decline in EM and executive function (EF), two important cognitive abilities, may have different roles in AD pathology vs. normal aging-related neurodegeneration that EM may be more sensitive to AD while EF may be more relevant to aging [20-23]. Other studies have developed composite scores that incorporating multiple cognitive domains [15], ignoring the fact that the longitudinal trajectories of these cognitive domains may not be identical.…”

Section: Introductionmentioning

confidence: 99%

Identification of Successful Cognitive Aging in the Alzheimer’s Disease Neuroimaging Initiative Study

Lin

Wang

et al. 2017

JAD

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The present prospective observational study aimed to identify the existence of successful cognitive agers among a group of well-defined cognitively healthy older adults (n = 354, mean age = 75 years), and to examine baseline individual-level predictors and associated health outcomes over time. Episodic memory (EM) and executive function (EF) composite scores and multiple health outcomes were obtained annually over 5 years. Potential individual-level predictors that were related to Alzheimer's pathology or genetic risk, neurodegeneration, and vascular risks were collected at baseline. Three latent classes with matched age and education were identified using growth mixture modeling: a group of participants who exhibited high, stable EM and EF (40.7% of the sample, “successful agers”); a group who had initial high cognitive performance that declined over time (21.2%, “declining agers”); and a group who had normal (EM) or poor (EF) but stable cognitive performance over time (38.1%, “low stable agers”). The group classification predicted significant differences in the incidence of global cognitive impairment, the development of at least one depressive symptom, and everyday functional impairment. Sex, Apolipoprotein E allele 4, beta-amyloid1-42, and t-tau significantly contributed to the difference in cognitive trajectories between the successful agers and the other two groups. Characterizing successful cognitive agers who are relatively resistant to both tau and amyloid pathology provides potential pathways for promoting successful cognitive aging and preventing cognitive decline.

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“…The RAVLT measures learning over trials as well as immediate and delayed recall. Whereas changes in both learning and immediate/delayed recall have been associated with healthy aging (Balthazar, Yasuda, Cendes, & Damasceno, 2010; Vyhnalek et al, 2014), we hypothesized that WM abnormalities would be more sensitive in predicting changes in delayed recall performance, which has been shown to be a strong predictor of conversion from healthy aging to MCI or AD (Albert et al, 2001; Hamel et al, 2015; Mistridis, Krumm, Monsch, Berres, & Taylor, 2015; Papp et al, 2015). …”

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confidence: 99%

Diffusion Tensor Imaging Predictors of Episodic Memory Decline in Healthy Elders at Genetic Risk for Alzheimer’s Disease

Lancaster

Seidenberg

Smith

et al. 2016

J Int Neuropsychol Soc

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Objective White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer’s disease (AD). Method Fifty-one cognitively intact elders (52% with family history of dementia and 33% possessing an Apolipoprotein E ε4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up. DTI scanning, conducted at study entry, examined fractional anisotropy and mean, radial and axial diffusion within three MTL WM tracts: uncinate fasciculus (UNC), cingulate-hippocampal (CHG), and fornix-stria terminalis (FxS). Correlations were performed between residualized change scores computed from RAVLT trials 1–5, immediate recall, and delayed recall scores and baseline DTI measures, MTL gray matter (GM) and WM volumes, demographics, and AD genetic and metabolic risk factors. Results Higher MTL mean and axial diffusivity at baseline significantly predicted 3-year changes in EM, whereas baseline MTL GM and WM volumes, family history, and metabolic risk factors did not. Both ε4 status and DTI correlated with change in immediate recall. Conclusions Longitudinal EM changes in cognitively intact, healthy elders can be predicted by disruption of the MTL WM microstructure. These results are derived from a sample with a disproportionately higher genetic risk for AD, suggesting that the observed WM disruption in MTL pathways may be related to early neuropathological changes associated with the preclinical stage of AD.

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The trajectory of cognitive decline in the pre-dementia phase in memory clinic visitors: findings from the 4C-MCI study

Cited by 45 publications

References 52 publications

On the path to 2025: understanding the Alzheimer’s disease continuum

On the path to 2025: understanding the Alzheimer’s disease continuum

Identification of Successful Cognitive Aging in the Alzheimer’s Disease Neuroimaging Initiative Study

Diffusion Tensor Imaging Predictors of Episodic Memory Decline in Healthy Elders at Genetic Risk for Alzheimer’s Disease

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