Influence of Alzheimer's disease genes on cognitive decline: the Guangzhou Biobank Cohort Study

Abstract Background：Vascular factors and mitochondria dysfunction contributeto thepathogenesis of Alzheimer’s Disease (AD).DL-3-n-butylphthalide (NBP)has an effect in protecting mitochondria and improving microcirculation. We investigated the effect of NBP in patients with mild-moderate AD already receiving donepezil.Methods: It was a prospective cohort study. 92 mild-moderate AD patients were classified into the donepezil alone group (n=43) or the donepezil combined NBP group (n=49) for 48 weeks. The primary outcome was change of Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog) from baseline after treatment 48 weeks. All patients were also evaluated with clinician’s interview-based impression of change plus caregiver input (CIBIC-plus), Alzheimer's disease cooperative study-activities of daily living (ADCS-ADL) and neuropsychiatric inventory (NPI) every 12 weeks. All patients were monitored for adverse events (AEs). The efficacy was analyzed using logistic regression analysis.Results:The univariate analysis showed that age wasolder in donepezil alone group(P=0.005), prevalence of hypertension was higher in donepezil alone group(P=0.026).The ADAS-cog score change from baseline in thedonepezil alone group was significant than that in the donepezil combined NBP group at 48 weeks(1.82±5.20 vs -0.38±4.46, P=0.048). The multivariate logistic regression analysis showed that between the 2 groups, there were significant differencesin changes on the ADAS-cog(OR=0.879,95% CI:[0.785,0.984],P=0.026),MMSE(OR=1.270,95% CI:[1.036,1.557],P=0.021), and ADCS-ADL(OR=1.067,95% CI:[1.002,1.136],P=0.042) but no significant differences for changes on the NPI(OR=0.955,95% CI:[0.901，1.013],P=0.125)and CIBIC-plus (OR=0.356,95% CI:[0.093,1.364],P=0.132). The occurrence of AEs was similar in the 2 groups.Conclusions:Over the 48-week treatment period, donepezil combined NBP group had slower cognitive decline and better activities of daily living in patients with mild to moderate AD. These indicated that the multi-target therapeutic effect of NBP may be a new choice for AD treatment.Trial registration:Clinical trial registration URL:https://clinicaltrials.gov/ct2/show/NCT02711683?term=NCT02711683&draw=2&rank=1ClinicalTrials.gov Identifier: NCT02711683. Date of registration: March 14,2016.

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Impact of coronary heart disease on cognitive decline in Alzheimer’s disease: a prospective longitudinal cohort study in primary care

British Journal of General Practice ◽

10.3399/bjgp16x688813 ◽

2016 ◽

Vol 67 (655) ◽

pp. e111-e117 ◽

Cited By ~ 14

Author(s):

Markus Bleckwenn ◽

Luca Kleineidam ◽

Michael Wagner ◽

Frank Jessen ◽

Siegfried Weyerer ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Coronary Heart Disease ◽

Cohort Study ◽

Heart Disease ◽

Cognitive Decline ◽

Late Onset ◽

Cardiovascular Prevention ◽

Clinical Dementia Rating ◽

Prospective Longitudinal

BackgroundArteriosclerotic disorders increase the risk of dementia. As they have common causes and risk factors, coronary heart disease (CHD) could influence the course of dementia.AimTo determine whether CHD increases the speed of cognitive decline in Alzheimer’s disease, and to discuss the potential for secondary cardiovascular prevention to modify this decline.Design and settingProspective multicentre cohort study in general practices in six cities in Germany.MethodParticipants were patients with probable mild-to-moderate Alzheimer’s dementia or mixed dementia (n = 118; mean age 85.6 [±3.4] years, range 80–96 years). The authors assessed the presence of CHD according to the family physicians’ diagnosis. Cognitive performance was measured during home visits for up to 3 years in intervals of 6 months, using Mini Mental State Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SoB). The authors also recorded whether patients died in the observation period.ResultsAt baseline, 65 patients (55%) had CHD and/or a heart condition following a myocardial infarction. The presence of CHD accelerated cognitive decline (MMSE, P<0.05) by about 66%, and reduced cognitive-functional ability (CDR-SoB, P<0.05) by about 83%, but had no impact on survival.ConclusionThe study shows that CHD has a significant influence on cognitive decline in older patients with late-onset dementia. The dementia process might therefore be positively influenced by cardiovascular prevention, and this possible effect should be further investigated.

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Cognitive decline related to substance consumption in a Colombian kindred with familial Alzheimer's disease: A retrospective cohort study

Alzheimer s & Dementia ◽

10.1002/alz.052860 ◽

2021 ◽

Vol 17 (S10) ◽

Author(s):

Claudia Patricia Ramos‐Perez ◽

Arvey Camilo Villalba ◽

Jenny Garcia ◽

Serggio Lanata ◽

Hugo Elias Lopez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cohort Study ◽

Cognitive Decline ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Familial Alzheimer’S Disease ◽

Familial Alzheimer's Disease ◽

Substance Consumption

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Faculty Opinions recommendation of Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717988744.793475383 ◽

2013 ◽

Author(s):

Karl Herholz ◽

Christopher Kobylecki

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cohort Study ◽

Cognitive Decline ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Amyloid Β ◽

Sporadic Alzheimer’S Disease

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Inter-network connectivity and amyloid-beta linked to cognitive decline in preclinical Alzheimer’s disease: a longitudinal cohort study

Alzheimer s Research & Therapy ◽

10.1186/s13195-018-0420-9 ◽

2018 ◽

Vol 10 (1) ◽

Cited By ~ 7

Author(s):

Roy W. E. Van Hooren ◽

◽

Joost M. Riphagen ◽

Heidi I. L. Jacobs

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cohort Study ◽

Cognitive Decline ◽

Amyloid Beta ◽

Network Connectivity ◽

Longitudinal Cohort Study ◽

Preclinical Alzheimer’S Disease ◽

Longitudinal Cohort

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Substance Use-Related Cognitive Decline in Families with Autosomal Dominant Alzheimer’s Disease: A Cohort Study

Journal of Alzheimer s Disease ◽

10.3233/jad-215169 ◽

2021 ◽

pp. 1-17

Author(s):

Claudia Ramos ◽

Camilo Villalba ◽

Jenny García ◽

Serggio Lanata ◽

Hugo López ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Substance Use ◽

Cohort Study ◽

Executive Function ◽

Cognitive Decline ◽

Verbal Fluency ◽

Genetic Variant ◽

Progression Rate ◽

Other Substances

Background: Cigarette smoking is a known risk factor for Alzheimer’s disease (AD). However, the association between neurodegeneration and other substances has not been fully determined. It is of vital importance to evaluate this relationship in populations at high risk of dementia. Since substance use possibly modifies the progression rate of cognitive decline, we studied this association in a unique and well-phenotyped cohort from the University of Antioquia: carriers of the PSEN1-E280A genetic variant. Objective: To determine the association between substance use and cognitive decline in carriers of the PSEN1-E280A genetic variant. Methods: A retrospective cohort study was conducted with 94 carriers and 69 noncarriers recruited between January 2019 and April 2020. A psychiatrist interviewed the participants using the Consumption of Alcohol, Cigarettes and other Substances questionnaire. The participants were also submitted to cognitive evaluation. The relationship between cognitive decline and substance use was explored through a mixed effects regression model. Results: There was an association between cigarettes and better performance on tasks related to perceptual organization, verbal fluency, and memory in carriers. Alcohol had a positive or negative effect on memory according to the type of alcoholic beverage. Results on marijuana use were no conclusive. Coffee was associated with progressive improvements in executive function and verbal fluency. Conclusion: Cigarette and alcohol were associated with an improvement of some cognitive assessments, possibly by a survival bias. In addition, coffee was related to improvements in executive function and language; therefore, its short-term neuroprotective potential should be studied.

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