Associations of Blood Pressure with Functional and Cognitive Changes in Patients with Alzheimer's Disease

2016 ◽  
Vol 41 (5-6) ◽  
pp. 314-323 ◽  
Author(s):  
Fabricio Ferreira de Oliveira ◽  
Elizabeth Suchi Chen ◽  
Marilia Cardoso Smith ◽  
Paulo Henrique Ferreira Bertolucci
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Late Onset ◽  
Angiotensin Receptor Blockers ◽  
Channel Blockers ◽  
Clinical Dementia Rating ◽  
Cognitive Changes ◽  
Converting Enzyme Inhibitors

Background: Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy. Methods: Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and APOE haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report. Results: Variations in systolic BP (-11.76 ± 17.1 mm Hg), diastolic BP (-4.92 ± 10.3 mm Hg) and pulse pressure (-6.84 ± 12.6 mm Hg) were significant after 1 year (n = 191; ρ < 0.01). For APOE4+ carriers, rises in systolic or diastolic BP improved Clinical Dementia Rating Scale Sum of Boxes scores (ρ < 0.04), with marginally significant improvements in Mini-Mental State Examination scores resulting from risen systolic (ρ = 0.069) or diastolic BP (ρ = 0.079), and in basic independence only regarding risen diastolic BP (ρ = 0.055). APOE4- carriers resisted any functional or cognitive effects of BP variations. No differences were found regarding any antihypertensive class for variations in BP or any test scores, regardless of APOE haplotypes. Conclusions: Targeting mild BP elevations brings better functional and cognitive results for APOE4+ carriers with AD.

Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia

2018 ◽  
Vol 15 (4) ◽  
pp. 386-398 ◽  
Author(s):  
Fabricio Ferreira de Oliveira ◽  
Elizabeth Suchi Chen ◽  
Marilia Cardoso Smith ◽  
Paulo Henrique Ferreira Bertolucci
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Cognitive Decline ◽  
Enzyme Inhibitors ◽  
Late Onset ◽  
Amyloid Β ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Alzheimer’S Disease Dementia

Background: While the angiotensin-converting enzyme degrades amyloid-β, angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer’s disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification. Methods: Consecutive late-onset AD patients were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with ACEis. Results: For 193 patients, minor allele frequencies were 0.497 for rs1800764 – C (44.6% heterozygotes) and 0.345 for rs4291 – T (38.9% heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and 124 used ACEis. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 – T and rs4291 – A, or for APOE4- carriers of rs1800764 – T or rs4291 – T, ACEis slowed cognitive decline independently of blood pressure variations. APOE4+ carriers were not responsive to treatment with ACEis. Conclusion: ACEis may slow cognitive decline for patients with AD, more remarkably for APOE4- carriers of specific ACE genotypes.

scholarly journals Caretaker Obstreperous Behavior Rating Scale

1997 ◽  
Vol 8 (S3) ◽  
pp. 321-324 ◽  
Author(s):  
Joan M. Swearer ◽  
David A. Drachman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Late Onset ◽  
Senile Dementia ◽  
Medical Personnel ◽  
Original Description ◽  
Behavior Rating Scale ◽  
Large Patient ◽  
Number Of Patients

Although Alzheimer's original description of the dementing disorder that bears his name emphasized the prominence of troublesome and disruptive behaviors, a systematic investigation of behavioral disturbances of dementia did not begin in earnest until the 1980s. At that time, as the neuropathologic identity of presenile Alzheimer's disease and late-onset “senile dementia” was recognized, the redefinition of Alzheimer's disease abruptly increased the number of patients diagnosed with this condition. Physicians and other medical personnel working with Alzheimer's disease patients recognized both the importance of abnormal behaviors in this now large patient population and the need to describe, classify, and quantify these behaviors.

scholarly journals Control of blood pressure and cardiovascular outcomes in type 2 diabetes

Open Medicine ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 304-323 ◽  
Author(s):  
Hernando Vargas-Uricoechea ◽  
Manuel Felipe Cáceres-Acosta
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Events ◽  
Angiotensin Receptor Blockers ◽  
Pharmacological Therapy ◽  
Current Evidence ◽  
Diabetic Patients ◽  
Channel Blockers ◽  
Converting Enzyme Inhibitors ◽  
Patients With Diabetes ◽  
The Impact

AbstractHigh blood pressure in patients with diabetes mellitus results in a significant increase in the risk of cardiovascular events and mortality. The current evidence regarding the impact of intervention on blood pressure levels (in accordance with a specific threshold) is not particularly robust. Blood pressure control is more difficult to achieve in patients with diabetes than in non-diabetic patients, and requires using combination therapy in most patients. Different management guidelines recommend initiating pharmacological therapy with values >140/90 mm/Hg; however, an optimal cut point for this population has not been established. Based on the available evidence, it appears that blood pressure targets will probably have to be lower than <140/90mmHg, and that values approaching 130/80mmHg should be recommended. Initial treatment of hypertension in diabetes should include drug classes demonstrated to reduce cardiovascular events; i.e., angiotensin converting-enzyme inhibitors, angiotensin receptor blockers, diuretics, or dihydropyridine calcium channel blockers. The start of therapy must be individualized in accordance with the patient's baseline characteristics, and factors such as associated comorbidities, race, and age, inter alia.

P1-172: COGNITIVE CHANGES ARE PHARMACOGENETICALLY MEDIATED BY ANGIOTENSIN-CONVERTING ENZYME INHIBITORS IN PATIENTS WITH ALZHEIMER'S DISEASE DEMENTIA

2006 ◽  
Vol 14 (7S_Part_6) ◽  
pp. P344-P345
Author(s):  
Fabricio Ferreira de Oliveira ◽  
Sandro Soares de Almeida ◽  
Elizabeth Suchi Chen ◽  
Marilia Arruda Cardoso Smith ◽  
Paulo Henrique Ferreira Bertolucci
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Cognitive Changes ◽  
Converting Enzyme Inhibitors ◽  
Alzheimer’S Disease Dementia

scholarly journals Efficacy and Limitations of rCBF-SPECT in the Diagnosis of Alzheimer’s Disease With Amyloid-PET

2019 ◽  
Vol 34 (5) ◽  
pp. 314-321
Author(s):  
Miwako Takahashi ◽  
Tomoko Tada ◽  
Tomomi Nakamura ◽  
Keitaro Koyama ◽  
Toshimitsu Momose
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Amyloid Pet ◽  
Clinical Dementia Rating ◽  
Positron Emission ◽  
Rcbf Spect

This study aimed to assess efficacy and limitations of regional cerebral blood flow imaging using single-photon emission computed tomography (rCBF-SPECT) in the diagnosis of Alzheimer’s disease (AD) with amyloid-positron emission tomography (amyloid-PET). Thirteen patients, who underwent both rCBF-SPECT and amyloid-PET after clinical diagnosis of AD or mild cognitive impairment, were retrospectively identified. The rCBF-SPECTs were classified into 4 grades, from typical AD pattern to no AD pattern of hypoperfusion; amyloid-beta (Aβ) positivity was assessed by amyloid-PET. Four patients were categorized into a typical AD pattern on rCBF-SPECT, and all were Aβ+. The other 9 patients did not exhibit a typical AD pattern; however, 4 were Aβ+. The Mini-Mental State Examination score and Clinical Dementia Rating scale were not significantly different between Aβ+ and Aβ– patients. A typical AD pattern on rCBF-SPECT can reflect Aβ+; however, if not, rCBF-SPECT has a limitation to predict amyloid pathology.

scholarly journals Predictors of rapid cognitive decline in Alzheimer's disease: results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing

2011 ◽  
Vol 24 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Alessandro Sona ◽  
Ping Zhang ◽  
David Ames ◽  
Ashley I. Bush ◽  
Nicola T. Lautenschlager ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Rating Scale ◽  
Cognitive Status ◽  
Imaging Biomarkers ◽  
Clinical Dementia Rating ◽  
Factors Associated ◽  
Biological Variables ◽  
Rapid Cognitive Decline

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.

scholarly journals Genetically Determined Blood Pressure, Antihypertensive Medications, and Risk of Alzheimer’s Disease: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Ya-Nan Ou ◽  
Yu-Xiang Yang ◽  
Xue-Ning Shen ◽  
Ya-Hui Ma ◽  
Shi-Dong Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Lower Risk ◽  
Mendelian Randomization ◽  
Angiotensin Receptor Blockers ◽  
Genome Wide Association Studies ◽  
Reverse Causality ◽  
Antihypertensive Medications ◽  
Genetically Determined

Abstract BackgroundObservational studies suggest that the use of antihypertensive medications (AHMs) is associated with a reduced risk of Alzheimer’s disease (AD); however, these findings may be biased by confounding and reverse causality. We aimed to explore the effects of blood pressure (BP) and lowering systolic BP (SBP) via the protein targets of different AHMs on AD through a two-sample Mendelian randomization (MR) approach.MethodsGenetic proxies from genome-wide association studies of BP traits and BP-lowering variants in genes encoding AHM targets were extracted. Estimates were calculated by inverse-variance weighted method as the main model. MR Egger regression and leave-one-out analysis were performed to identify potential violations. ResultsThere was limited evidence that genetically predicted SBP/diastolic BP level affected AD risk based on 400/398 single nucleotide polymorphisms (SNPs), respectively (all P>0.05). Suitable genetic variants for β-blockers (1 SNP), angiotensin receptor blockers (1 SNP), calcium channel blockers (CCBs, 45 SNPs) and thiazide diuretics (5 SNPs) were identified. Genetic proxies for CCB [odds ratio (OR)=0.959, 95% confidence interval (CI)=0.941-0.977, P<0.001], and overall use of AHMs (OR=0.961, 95% CI=0.944-0.978, P<0.001, SNPs=52) were associated with a lower risk of AD. No notable heterogeneity and directional pleiotropy were identified (all P>0.05). No single SNP was driving the observed effects. ConclusionsThis MR analysis found robust evidence that genetically determined lowering BP was associated with a lower risk of AD and CCB was identified as a promising strategy for AD prevention.

Arterial stiffness: from isolated systolic hypertension to syncope

ESC CardioMed ◽  
2018 ◽  
pp. 2971-2976
Author(s):  
Jerzy Gąsowski ◽  
Chirag Bavishi ◽  
Franz H Messerli
Keyword(s):  
Blood Pressure ◽  
Pulse Pressure ◽  
Systolic Hypertension ◽  
Pulse Wave ◽  
Angiotensin Receptor Blockers ◽  
The Elderly ◽  
Channel Blockers ◽  
Isolated Systolic Hypertension ◽  
Converting Enzyme Inhibitors ◽  
European Guidelines

Isolated systolic hypertension (ISH) is the predominant form of hypertension in the elderly. The pathophysiology includes a plethora of factors; however, the stiffening of large arteries, leading to wider pulse pressure and faster propagation of the pressure pulse wave, are at the core of the disease. It has been shown that higher systolic blood pressure (SBP), pulse pressure, and pulse wave velocity are associated with a greater risk of cardiovascular complications, including a greater risk of dementia. In elderly patients, the relationship between SBP and the risk of mortality starts increasing at about 160 mmHg. A number of clinical trials were performed in populations of patients which included the elderly, however only four trials were specifically dedicated to answer the question of whether the active treatment of ISH (SHEP, Syst-Eur, Syst-China) or treatment of octogenarian hypertensive patients (HYVET) lowers cardiovascular risk in the elderly patient. They all showed that regimens based on thiazide-like diuretics, dihydropyridine calcium channel blockers, or angiotensin-converting enzyme inhibitors are capable of reducing the risk along with the appropriate reduction of SBP. This is widely reflected in the current European guidelines, with the addition of angiotensin receptor blockers. Nevertheless, the debate on the appropriate blood pressure goal is ongoing. However, none of the trials in the elderly had an average SBP lowered to less than 140 mmHg, and the overwhelming evidence suggests that in patients above the age of 70 with overt cardiovascular disease, a SBP less than 130 mmHg may be associated with an increase in risk.

scholarly journals Education, leisure activities and cognitive and functional ability of Alzheimer's disease patients: A follow-up study

2013 ◽  
Vol 7 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Margarida Sobral ◽  
Constança Paúl
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Functional Ability ◽  
Rating Scale ◽  
Leisure Activities ◽  
Functional Decline ◽  
Clinical Dementia Rating ◽  
High Participation ◽  
Relevant Variables

ABSTRACT Education and participation in leisure activities appear to be highly relevant variables in Alzheimer's disease (AD) and usually form the basis of the Cognitive Reserve construct. Objective: [A] To determine the association between education, cognitive and functional ability of AD patients; [B] To determine the association between participation in leisure activities and cognitive and functional ability of AD patients; [C] To evaluate the association of education and participation in leisure activities in the course of AD. Methods: Functional and neuropsychological abilities of 120 outpatients with probable AD were evaluated at baseline, at 36 and 54 months. Data collected at baseline included socio-demographics, clinical variables, education and frequency of participation in leisure activities throughout life. All participants and/or caregivers answered the questionnaire, "Participation in leisure activities throughout life" while patients completed the MMSE, the Clinical Dementia Rating scale, neuropsychological tests from the Lisbon Screening for Dementia Assessment, Barthel Index and Lawton and Brody's Index. Results: AD patients with higher levels of education achieved better results on cognitive tests. The participants with higher participation in leisure activities exhibited better results on cognitive and functional tests than those with lower participation. The disease progression was linear and progressed similarly regardless of the level of education of participants. However, the results suggest a slower disease progression in patients with a higher level of participation in leisure activities throughout their lives. Conclusion: AD patients with high education and high participation in leisure activities may benefit from a slower cognitive and functional decline after diagnosis of AD.

scholarly journals 97 Potentially Inappropriate Medications in Patients with Alzheimer’s Disease: Data from NILVAD

2019 ◽  
Vol 48 (Supplement_3) ◽  
pp. iii1-iii16
Author(s):  
Claire Murphy ◽  
Adam H Dyer ◽  
Brian Lawlor ◽  
Sean P Kennelly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Drug Events ◽  
Rating Scale ◽  
Secondary Analysis ◽  
Median Number ◽  
Potentially Inappropriate Medications ◽  
Clinical Dementia Rating ◽  
Start Criteria ◽  
Inappropriate Medications

Abstract Background Prescription of Potentially Inappropriate Medications (PIMs) is common in older adults and is associated with adverse drug events, hospitalisation and mortality. Less well described are the patterns and predictors of PIM usage in patients with Alzheimer’s Disease (AD), a patient group who may be particularly vulnerable to polypharmacy and medication associated adverse events. Methods Secondary analysis of the NILVAD trial, an international phase three trial of Nilvadipine in mild/moderate AD. The v2 STOPP/START criteria were individually applied by a physician to each participant’s medication list and cross-reference with their medical history to identify PIM usage. Predictors of PIM usage were modelled using binary logistic regression. Results Five-hundred and ten patients with AD were included (mean age 72.8 +/-8.3 years; 62% female). The median number of prescribed medications was 5 (IQR 3-7). Over half (55.5%) were prescribed at least one PIM, whilst a minority of patients (14.8%) were prescribed three or more PIMs. The most frequent PIMs were benzodiazepines >4 weeks without indication (n = 55), long-term Proton-Pump Inhibitor (PPI) use without appropriate indication (n = 49), use of non-steroidal analgesics without use of PPI (n=19) and antimuscarinic use in dementia (n= 18). On multivariate analysis, significant predictors of PIM use were higher total number of medications (p=0.001; OR 1.52; 1.36-1.59) in addition to greater AD severity, as rated using the Clinical Dementia Rating Scale Sum-of-Boxes (CDR-sb) (p=0.024; OR 1.18; 1.02-1.35). Conclusion The majority of older patients with AD were prescribed at least one PIM. Usage of PIMs was associated with greater number of medications and increased dementia severity. Particularly concerning is the potentially inappropriate use of benzodiazepines and anti-muscarinic agents in this population, given recent evidence for the adverse cognitive profile associated with these medications. De-prescribing and medication review interventions aimed particularly at patients with AD are warranted.

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