Progression of Alzheimer’s Disease: A Longitudinal Study in Norwegian Memory Clinics

Eldholm, Rannveig Sakshaug; Barca, Maria Lage; Persson, Karin; Knapskog, Anne-Brita; Kersten, Hege; Engedal, Knut; Selbæk, Geir; Brækhus, Anne; Skovlund, Eva; Saltvedt, Ingvild

doi:10.3233/jad-170436

Cited by 46 publications

(45 citation statements)

References 33 publications

(57 reference statements)

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“…Our results agree, in part, with a recent longitudinal study from Norway by Eldholm et al (2018). 33 Similar to our finding that the majority of AD patients progresses relatively slowly, this study showed that approximately half of their sample consisted of slow progressors, defined as showing less than 1 point worsening in CDR-sb per year. As in our study, the slow progressors from the Norwegian cohort scored better on cognitive tests and the CDR-sb at diagnosis, as compared to the more rapid progressors.…”

Section: Discussionsupporting

confidence: 87%

“…It should be noted that the study by Eldholm et al (2018) included only a single follow-up measurement after a mean follow-up time of 2 years, and its sample consisted of both AD and MCI patients. 33 …”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that the study by Eldholm et al included only a single follow-up measurement after a mean follow-up time of 2 years, and its sample consisted of both AD and MCI patients. 33 The strengths of the present study include its large sample of patients with a clinical diagnosis of AD and the inclusion of both cognitive and functional measures of AD progression, reflecting the multidimensional impact of AD. In addition, the use of GMMs allowed us to compare non-linear change rates across subpopulations, without using an arbitrary cut-off for rapid decline.…”

Section: Replication Of the Cache County Modelmentioning

confidence: 99%

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Cognitive and functional progression in Alzheimer disease: A prediction model of latent classes

Haaksma

Calderón‐Larrañaga

Rikkert

et al. 2018

Int J Geriat Psychiatry

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Objective We sought to replicate a previously published prediction model for progression, developed in the Cache County Dementia Progression Study (CCDPS), using a clinical cohort from the National Alzheimer’s Coordinating Center. Methods We included 1120 incident AD cases with at least one assessment after diagnosis, originating from 31 Alzheimer Disease centers from the United States. Trajectories of the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating sum of boxes (CDR-sb) were modeled jointly over time using parallel-process growth mixture models in order to identify latent classes of trajectories. Bias-corrected multinomial logistic regression was used to identify baseline predictors of class membership and compare these with the predictors found in the CCDPS. Results The best fitting model contained three classes; class 1 was the largest (63%) and showed the slowest progression on both MMSE and CDR-sb. Classes 2 (22%) and 3 (15%) showed moderate and rapid worsening, respectively. Significant predictors of membership in classes 2 and 3, relative to class 1, were worse baseline MMSE and CDR-sb, higher education and lack of hypertension. Combining all previously mentioned predictors yielded areas under the ROC curve of 0.70 and 0.75 for classes 2 and 3, relative to class 1. Conclusions Our replication study confirmed that it is possible to predict trajectories of progression in AD with relatively good accuracy. The class distribution was comparable with the original study, with most individuals being members of a class with stable or slow progression. This is important for informing newly diagnosed AD patients and their caregivers.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Replication Of the Cache County Modelmentioning

confidence: 99%

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Cognitive and functional progression in Alzheimer disease: A prediction model of latent classes

Haaksma

Calderón‐Larrañaga

Rikkert

et al. 2018

Int J Geriat Psychiatry

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“…Notably, although TMEM106B variants do not associate with risk for developing the TDP-43 proteinopathy ALS, they do associate with cognitive impairment among individuals with manifest ALS. In this context, we point out that other genetic variants associated with increased risk for developing a disease have been associated with both faster progression of that disease (eg, APOE4 alleles in AD) 26 and slower progression (eg, LRRK2 G2019S in PD), 27 underlining the importance of formal evaluation in longitudinal studies. 3,25 We find here that TMEM106B variants that increase risk for FTLD-TDP may also associate with a faster rate of cognitive decline in clinically diagnosed FTD patients, with positive findings in the bvFTD subgroup as well.…”

Section: Discussionmentioning

confidence: 98%

TMEM106B Effect on cognition in Parkinson disease and frontotemporal dementia

Tropea

Mak

Guo

et al. 2019

Annals of Neurology

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Objective: Common variants near TMEM106B associate with risk of developing frontotemporal dementia (FTD). Emerging evidence suggests a role for TMEM106B in neurodegenerative processes beyond FTD. We evaluate the effect of TMEM106B genotype on cognitive decline across multiple neurogenerative diseases. Methods: We longitudinally followed 870 subjects with diagnoses of Parkinson disease (PD; n = 179), FTD (n = 179), Alzheimer disease (AD; n = 300), memory-predominant mild cognitive impairment (MCI; n = 75), or neurologically normal control subjects (NC; n = 137) at the University of Pennsylvania (UPenn). All participants had annual Mini-Mental State Examination (MMSE; median follow-up duration = 3.0 years) and were genotyped at TMEM106B index single nucleotide polymorphism rs1990622. Genotype effects on cognition were confirmed by extending analyses to additional cognitive instruments (Mattis Dementia Rating Scale-2 [DRS-2] and Montreal Cognitive Assessment [MoCA]) and to an international validation cohort (Parkinson's Progression Markers Initiative [PPMI], N = 371).Results: The TMEM106B rs1990622 T allele, linked to increased risk of FTD, associated with greater MMSE decline over time in PD subjects but not in AD or MCI subjects. For FTD subjects, rs1990622 T associated with more rapid decrease in MMSE only under the minor-allele, rs1990622 C , dominant model. Among PD patients, rs1990622 T carriers from the UPenn cohort demonstrated more rapid longitudinal decline in DRS-2 scores. Finally, in the PPMI cohort, TMEM106B risk allele carriers demonstrated more rapid longitudinal decline in MoCA scores. Interpretation: Irrespective of cognitive instrument or cohort assessed, TMEM106B acts as a genetic modifier for cognitive trajectory in PD. Our results implicate lysosomal dysfunction in the pathogenesis of cognitive decline in 2 different proteinopathies.

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“…Furthermore, the physical and cognitive tests were first performed at the baseline BL examination and could be sensitive to changes during this time period or due to the event of admission. However, the GMHR and CDR have shown to be stable over time [39][40][41]. Moreover, caregiver-reported data from the RUD questionnaire may have yielded inaccuracies in the extent of formal and informal care.…”

Section: Limitations and Strengthsmentioning

confidence: 99%

Informal and formal care among persons with dementia immediately before nursing home admission.

Ydstebø

Benth

Bergh

et al. 2019

Preprint

Self Cite

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Background: This study assesses the use of formal and informal care resources among home-dwelling persons with dementia during the last month before nursing home admission. It also describes providers of informal care and assesses clinical and sociodemographic factors associated with the use of care stratified by living situation. Methods: In this cross-sectional study, data were collected from 47 nursing homes in four counties in Norway from January 2012 to August 2014. The subjects were persons with dementia who were newly admitted to a permanent nursing home. The main outcome measures were the use of formal care and informal care by the family caregiver and the extended social network. Results: A total of 395 persons were included. The amount of informal care provided by the family caregiver was 141.9 hours (SD=227.4). Co-resident patients received five times more informal care than non-co-residents. Informal care from the extended social network was provided to 212 patients (53.7%) with a mean of 5.6 (SD=11.2) hours per month. Formal care was provided to 52.7% of the patients with a mean of 18.0 (SD=50.1) hours per month. Co-residency was significantly associated with more informal care, and the associations varied with respect to age, relation to the caregiver, and the caregiver’s working situation. Good/excellent general health was associated with less formal care. Conclusion: Persons with dementia on the verge of admission to a nursing home are mostly supported by the family caregiver, and the use of informal care is particularly high among co-residents. Future research should explore the unrealized care potential in extended social networks, as well as the potential for increasing the number of recipients and utilization of formal care services directed at persons with dementia and their caregivers in order to delay nursing home admission.

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Progression of Alzheimer’s Disease: A Longitudinal Study in Norwegian Memory Clinics

Cited by 46 publications

References 33 publications

Cognitive and functional progression in Alzheimer disease: A prediction model of latent classes

Cognitive and functional progression in Alzheimer disease: A prediction model of latent classes

TMEM106B Effect on cognition in Parkinson disease and frontotemporal dementia

Informal and formal care among persons with dementia immediately before nursing home admission.

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