Efficacy of SSRIs on cognition of Alzheimer's disease patients treated with cholinesterase inhibitors

ABSTRACTBackground: This study examines the joint effect on cognition of selective serotonin re-uptake inhibitors (SSRIs) and cholinesterase inhibitors (AChEIs) in depressed patients affected by Alzheimer's disease (AD) living at home.Methods: The study was conducted in two different outpatient neurological clinics. 338 patients with probable AD were treated with ChEis (donepezil, rivastigmine and galantamine) as per the clinician's judgment and were observed for nine months. At study entry, participants underwent a multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All patients were evaluated at baseline, after one (T1), three (T2) and nine months (T3). Patients were grouped in three different categories (patients not depressed and not treated with SSRIs, patients depressed and treated with SSRIs, and patients depressed but not treated with SSRIs).Results: At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score from baseline to nine months showed that depressed patients not treated worsened in comparison with those not depressed and not treated with SSRIs (mean change −0.8 ± 2.3 vs 0.04 ± 2.9; p = 0.02) and patients depressed and treated with SSRI (mean change −0.8 ± 2.3 vs 0.1 ± 2.5; p = 0.03).Conclusions: In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition.

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Initial cognitive response to cholinesterase inhibitors and subsequent long-term course in patients with mild Alzheimer's disease

International Psychogeriatrics ◽

10.1017/s1041610215000289 ◽

2015 ◽

Vol 27 (8) ◽

pp. 1323-1333 ◽

Cited By ~ 8

Author(s):

Erika Droogsma ◽

Dieneke van Asselt ◽

Marjolein Diekhuis ◽

Nic Veeger ◽

Cornelis van der Hooft ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cholinesterase Inhibitors ◽

Mmse Score ◽

Initial Response ◽

Community Dwelling ◽

Marginal Model ◽

Cognitive Response ◽

Chei Treatment

ABSTRACTBackground:Some guidelines recommend to discontinue treatment with cholinesterase inhibitors (ChEIs) in patients with Alzheimer's disease (AD) without an initial response to ChEI treatment. Evidence supporting this recommendation, however, is limited. This study aimed to investigate the relation between the initial cognitive response to ChEI treatment and the subsequent long-term course of cognition of AD patients.Methods:The Frisian Alzheimer's Disease Cohort study is a retrospective longitudinal study of 576 community-dwelling AD patients treated with ChEIs in a “real-life” setting at a large memory clinic. A repeated measures analysis using a marginal model (population based averaged model) was applied to investigate whether there is a difference in the subsequent long-term course of cognition (Mini-Mental State Examination (MMSE)) between initial non-responders and responders. Absence of an initial response was defined as a lower MMSE score after the first six months of treatment compared to baseline, a positive response as the same or a higher MMSE score.Results:At baseline, median age was 80 years and the median MMSE score 23. Non-responders showed a slower rate of cognitive decline in the three subsequent years than responders, with a mean annual MMSE decline of 0.9 points versus 1.2 points, respectively (p < 0.0001).Conclusions:Our results suggest that it is not appropriate to discontinue ChEI treatment solely based on the absence of an initial cognitive response.

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Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557518666181102102816 ◽

2019 ◽

Vol 19 (8) ◽

pp. 688-705

Author(s):

Taibi Ben Hadda ◽

Abdur Rauf ◽

Hsaine Zgou ◽

Fatma Sezer Senol ◽

Ilkay Erdogan Orhan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cholinesterase Inhibitors ◽

Metal Accumulation ◽

Microtiter Plate ◽

Metal Chelation ◽

Carbonyl Derivatives ◽

Cholinesterase Inhibitory Activity ◽

Inhibitory Potential

Background:Since deficit of acetylcholine has been evidenced in the Alzheimer’s disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.Method:In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.Results and Conclusion:All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

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Effects of Cholinesterase Inhibitors on the Activities and Protein Levels of Cholinesterases in the Cerebrospinal Fluid of Patients with Alzheimer's disease: A Review of Recent Clinical Studies

Current Alzheimer Research ◽

10.2174/1567209198607252050 ◽

2009 ◽

Vol 999 (999) ◽

pp. 1-6

Author(s):

Taher Darreh-Shori

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Clinical Studies ◽

Cholinesterase Inhibitors ◽

Protein Levels

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Joint Effect of ABCA7 rs4147929 and Body Mass Index on Progression from Mild Cognitive Impairment to Alzheimer’s Disease: The Shanghai Aging Study

Current Alzheimer Research ◽

10.2174/1567205017666200317095608 ◽

2020 ◽

Vol 17 (2) ◽

pp. 185-195

Author(s):

Jianxiong Xi ◽

Ding Ding ◽

Qianhua Zhao ◽

Xiaoniu Liang ◽

Li Zheng ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Body Mass Index ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Body Mass ◽

Joint Effect ◽

Genome Wide Association Studies ◽

Risk Genotype ◽

Aging Study

Background: Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies. Methods: We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese community cohort. Conclusion: Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316 participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the log-rank test and Cox regression model. Results: Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio [HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs. non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7 rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However, a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight BMI and AG/AA of ABCA7 rs4147929). Conclusion: ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their risk for incident AD.

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Significant effects of cholinesterase inhibitors on tau pathology in the Alzheimer's disease continuum: An in vivo positron emission tomography study

International Journal of Geriatric Psychiatry ◽

10.1002/gps.5522 ◽

2021 ◽

Author(s):

Fumihiko Yasuno ◽

Hiroyuki Minami

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Positron Emission Tomography ◽

Cholinesterase Inhibitors ◽

Emission Tomography ◽

Positron Emission Tomography Study ◽

Tau Pathology ◽

Positron Emission

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Lighting and Alzheimer’s disease and related dementias: Spotlight on sleep and depression

Lighting Research and Technology ◽

10.1177/14771535211005835 ◽

2021 ◽

Vol 53 (5) ◽

pp. 405-422

Author(s):

MG Figueiro ◽

HC Kales

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Neurodegenerative Disease ◽

Sleep Disturbances ◽

Well Being ◽

Pharmacological Intervention ◽

Negative Effects ◽

Health And Well Being ◽

Positive Results

Alzheimer’s disease and related dementias is the collective term for a progressive neurodegenerative disease for which there is presently no cure. This paper focuses on two symptoms of the disease, sleep disturbances and depression, and discusses how light can be used as a non-pharmacological intervention to mitigate their negative effects. Bright days and dark nights are needed for health and well-being, but the present components of the built environment, especially those places where older adults spend most of their days, are too dimly illuminated during the day and too bright at night. To be effective light needs to be correctly specified, implemented and measured. Yet, without the appropriate specification and measurement of the stimulus, researchers will not be able to successfully demonstrate positive results in the field, nor will lighting designers and specifiers have the confidence to implement lighting solutions for promoting better sleep and mood in this population.

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