Predicting rapid cognitive decline in Alzheimer's disease patients using quantitative EEG markers and neuropsychological test scores

ABSTRACTBackground: The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients.Methods: We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as with and without subjects who had died or were too severely affected to be interviewed at 18 months and after, both including and excluding subjects whose AD diagnosis was “possible” AD. We sought correlations between rapid cognitive decline and demographic, clinical and biological variables.Results: Of the 211 AD patients recruited at baseline, we had available data for 156 (73.9%) patients at 18 months. Fifty-one patients were considered rapid cognitive decliners (32.7%). A higher Clinical Dementia Rating scale (CDR) and higher CDR “sum of boxes” score at baseline were the major predictors of rapid cognitive decline in this population. Furthermore, using logistic regression model analysis, patients treated with a cholinesterase inhibitor (CheI) had a higher risk of being rapid cognitive decliners, as did males and those of younger age.Conclusions: Almost one third of patients satisfying established research criteria for AD experienced rapid cognitive decline. Worse baseline functional and cognitive status and treatment with a CheI were the major factors associated with rapid cognitive decline over 18 months in this population.

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Rapid cognitive decline in Alzheimer's disease: a literature review

International Review of Psychiatry ◽

10.3109/09540261.2013.859128 ◽

2013 ◽

Vol 25 (6) ◽

pp. 650-658 ◽

Cited By ~ 23

Author(s):

Alessandro Sona ◽

Kathryn A. Ellis ◽

David Ames

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Literature Review ◽

Cognitive Decline ◽

Rapid Cognitive Decline

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The Pathology of Rapid Cognitive Decline in Clinically Diagnosed Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-190302 ◽

2019 ◽

Vol 70 (4) ◽

pp. 983-993 ◽

Cited By ~ 4

Author(s):

Christin Nance ◽

Aaron Ritter ◽

Justin B. Miller ◽

Brittany Lapin ◽

Sarah J. Banks

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Rapid Cognitive Decline

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O2-04-07: Most rapid cognitive decline in APOE4 negative Alzheimer's disease with early onset

Alzheimer s & Dementia ◽

10.1016/j.jalz.2009.05.349 ◽

2009 ◽

Vol 5 (4S_Part_4) ◽

pp. P111-P112

Author(s):

Wiesje M. van der Flier ◽

Annelies E. van der Vlies ◽

Esther L. Koedam ◽

Yolande A.L. Pijnenburg ◽

Jos W.R. Twisk ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Early Onset ◽

Rapid Cognitive Decline

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P2-348: The effect of rapid cognitive decline in MCI and Alzheimer's disease on level of dependence, resource utilization, carer satisfaction, burden and attitudes to aging

Alzheimer s & Dementia ◽

10.1016/j.jalz.2013.05.996 ◽

2013 ◽

Vol 9 ◽

pp. P487-P488

Author(s):

Carly Copolov ◽

Karra Harrington ◽

Briony Dow ◽

Melanie Joosten ◽

Stephanie Rainey-Smith ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Resource Utilization ◽

Rapid Cognitive Decline

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Trajectories of cognitive decline in Alzheimer's disease

International Psychogeriatrics ◽

10.1017/s1041610209991001 ◽

2009 ◽

Vol 22 (2) ◽

pp. 281-290 ◽

Cited By ~ 78

Author(s):

Patricia A. Wilkosz ◽

Howard J. Seltman ◽

Bernie Devlin ◽

Elise A. Weamer ◽

Oscar L. Lopez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Complex Disease ◽

Latent Class ◽

Rating Scale ◽

Late Onset ◽

Psychotic Symptoms ◽

Concomitant Variables ◽

Rapid Cognitive Decline

ABSTRACTBackground: Late-onset Alzheimer disease (LOAD) is a clinically heterogeneous complex disease defined by progressively disabling cognitive impairment. Psychotic symptoms which affect approximately one-half of LOAD subjects have been associated with more rapid cognitive decline. However, the variety of cognitive trajectories in LOAD, and their correlates, have not been well defined. We therefore used latent class modeling to characterize trajectories of cognitive and behavioral decline in a cohort of AD subjects.Methods: 201 Caucasian subjects with possible or probable Alzheimer's disease (AD) were evaluated for cognitive and psychotic symptoms at regular intervals for up to 13.5 years. Cognitive symptoms were evaluated serially with the Mini-mental State Examination (MMSE), and psychotic symptoms were rated using the CERAD behavioral rating scale (CBRS). Analyses undertaken were latent class mixture models of quadratic trajectories including a random intercept with initial MMSE score, age, gender, education, and APOE ϵ4 count modeled as concomitant variables. In a secondary analysis, psychosis status was also included.Results: AD subjects showed six trajectories with significantly different courses and rates of cognitive decline. The concomitant variables included in the best latent class trajectory model were initial MMSE and age. Greater burden of psychotic symptoms increased the probability of following a trajectory of more rapid cognitive decline in all age and initial MMSE groups. APOE ϵ4 was not associated with any trajectory.Conclusion: Trajectory modeling of longitudinal cognitive and behavioral data may provide enhanced resolution of phenotypic variation in AD.

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Factors Affecting Rapid Cognitive Decline in Patients with Alzheimer’s Disease: A Longitudinal Follow-Up Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18168576 ◽

2021 ◽

Vol 18 (16) ◽

pp. 8576

Author(s):

Chih-Chuan Pan ◽

Che-Sheng Chu ◽

Chien-Liang Chen ◽

Yao-Chung Chuang ◽

Nai-Ching Chen

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Protective Factor ◽

Proportional Hazards ◽

Acetylcholinesterase Inhibitors ◽

Cox Proportional Hazards ◽

Research Database ◽

Clinical Dementia Rating ◽

Rapid Cognitive Decline

We investigated the preventive and risk factors of rapid cognitive decline in patients with Alzheimer’s disease (AD). Using the Chang Gung Research Database (CGRD), we enrolled patients with AD aged over 65 years between 1 January 2001 and 30 May 2019, and followed up for at least two years. Rapid cognitive decline was defined by a Mini-Mental State Examination (MMSE) score decline of ≥4 in 2 years. A longer prescription of acetylcholinesterase inhibitors (AChEIs) was defined as 22 months based on the median treatment duration of the cohorts. The Cox proportional hazards regression model adjusted for age, sex, medication, and physical comorbidities was used to examine the candidate risk and protective factors. We analyzed data from 3846 patients with AD (1503 men, 2343 women) with a mean age and percentage of females of 77.8 ± 6.2 years and 60.9%, respectively. The mean duration of patients with AD receiving AChEIs was 658.7 ± 21.9 days. In general, 310 patients with AD showed a rapid cognitive decline, accounting for 8.1%. Treatment of a consecutive AChEI prescription for >22 months in patients with AD was a protective factor against rapid cognitive decline (adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.33–0.52, p < 0.001). Patients with AD aged >85 years (aHR = 0.53, 95% CI = 0.36–0.79, p < 0.01) and aged 75–85 years (aHR = 0.73, 95% CI = 0.57–0.93, p < 0.05) had a significantly lower risk of rapid cognitive decline than those aged 65–75 years. Additionally, patients with mild and moderate AD (clinical dementia rating (CDR = 1, aHR = 1.61, 95% CI = 1.26–2.07, p < 0.001; CDR = 2, aHR = 2.64, 95% CI = 1.90–3.65, p < 0.001) were more likely to have rapid cognitive decline than those with early AD (CDR = 0.5). Sex, medication with different types of AChEIs, and physical comorbidities were not associated with rapid cognitive decline. These findings indicate that it is important to maintain longer consecutive AChEI prescriptions in patients with AD to prevent cognitive decline.

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