Cognitive and functional progression of dementia in two longitudinal studies

Abstract

Objectives Previous studies have identified several subgroups (ie, latent trajectories) with distinct disease progression among people with dementia. However, the methods and results were not always consistent. This study aims to perform a coordinated analysis of latent trajectories of cognitive and functional progression in dementia across two datasets. Methods Included and analyzed using the same statistical approach were 1628 participants with dementia from the US National Alzheimer's Coordinating Center (NACC) and 331 participants with dementia from the Dutch Clinical Course of Cognition and Comorbidity study (4C‐Study). Trajectories of cognition and instrumental activities of daily living (IADL) were modeled jointly in a parallel‐process growth mixture model. Results Cognition and IADL tended to decline in unison across the two samples. Slow decline in both domains was observed in 26% of the US sample and 74% of the Dutch sample. Rapid decline in cognition and IADL was observed in 7% of the US sample and 26% of the Dutch sample. The majority (67%) of the US sample showed moderate cognitive decline and rapid IADL decline. Conclusions Trajectories of slow and rapid dementia progression were identified in both samples. Despite using the same statistical methods, the number of latent trajectories was not replicated and the relative class sizes differed considerably across datasets. These results call for careful consideration when comparing progression estimates in the literature. In addition, the observed discrepancy between cognitive and functional decline stresses the need to monitor dementia progression across multiple domains.

Trajectories and risk factors of dementia progression: a memory clinic cohort followed up to 3 years from diagnosis

“…Rapid progression was associated with older age, lower cognitive function, and more-pronounced NPS at the time of diagnosis. Our findings are in agreement with those of other studies showing heterogeneity in the progression rate of patients with dementia (Eldholm et al, 2018a;Haaksma et al, 2018;Melis et al, 2019;Song et al, 2018;Wang et al, 2019). The trajectory groups in our sample differed regarding baseline cognitive and functional abilities, indicating the patients were at different stages of dementia at baseline.…”

“…Dementia disorders progress, leading to disability and, ultimately, death (Strand et al, 2018(Strand et al, , 2019. Studies have indicated that subgroups of patients with dementia follow different trajectories of progression, with a large proportion progressing slowly, especially in the earlier stages (Eldholm et al, 2018a;Melis et al, 2019;Song et al, 2018;Wang et al, 2019). Several risk factors for rapid progression at the time of diagnosis have been identified, but the findings are conflicting, and different approaches used and risk factors assessed make it challenging to compare results (Melis et al, 2019).…”

“…Different methods and assessment scales are used to measure progression, thereby hindering comparison (Melis et al, 2019;Wang et al, 2019). Most studies have used the change in Mini-Mental State Examination (MMSE) or the Clinical Dementia Rating Scale (CDR), while changes in activities of daily living (ADLs), NPS load, and length of time to nursing home admission or to death have been used less frequently (Melis et al, 2019).…”

Identification of and a Prediction Model for Cognitive Trajectories in Patients With Mild Cognitive Impairment Due to Alzheimer’s Disease

“…Taken together, our analysis provides novel insights into the heterogeneous cognitive trajectories among Aβ + MCI patients, which further facilitates the effective strati cation of Aβ + MCI participants in Aβ-targeted clinical trials.Our rst major nding was that Aβ + MCI patients were classi ed into three groups based on changes in cognitive performance by trajectory analysis: slow, intermediate, and fast decliners. Previous studies have reported several latent patterns of cognitive change in patients with varying severity of cognitive impairment[21,[43][44][45][46][47][48]. Our nding was consistent with those of some previous studies showing that individuals with MCI, regardless of the presence or absence of amyloid, had several distinct trajectories of cognitive progression…”

Clinical meaningfulness of subtle cognitive decline on longitudinal testing in preclinical AD

“…The Alzheimer's disease (AD) continuum involves a protracted asymptomatic phase starting with the accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles, followed by subtle yet increasingly persistent cognitive decline, functional impairment, and ultimately the dementia syndrome . At the symptomatic stages of disease, cognitive and functional decline tend to occur in unison and regulators have historically required co‐primary outcomes of cognition and function to ensure the clinical meaningfulness of the cognitive effect on functional progression. Advances in our ability to visualize AD neuropathology in vivo have provided the opportunity for early detection during the preclinical phase and have spurred secondary prevention trials to minimize cognitive decline in asymptomatic but at‐risk individuals.…”