Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(9), С. 3059 - 3059

Опубликована: Апрель 26, 2020

Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic the treatment of behavioral disorders (BDs), and different categories concomitant disorders. Demented may take >6–10 drugs/day consequent risk drug–drug interactions adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, pleiotropic genes redundantly promiscuously regulated epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, CYP3A4/5 geno-phenotypes are involved in metabolism over 90% currently used dementia, only 20% population an extensive metabolizer this tetragenic cluster. ADRs associated drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, antiepileptic can be minimized means pharmacogenetic screening prior treatment. These substrates, inhibitors, or inducers 58, 37, 42 enzyme/protein gene products, respectively, transported 40 protein transporters. APOE reference most studies. APOE-3 carriers best responders APOE-4 worst responders; likewise, CYP2D6-normal metabolizers CYP2D6-poor responders. incorporation pharmacogenomic strategies a personalized effective option optimize limited therapeutic resources reduce unwanted side-effects.

Язык: Английский

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Chaudhuri’s Dashboard of Vitals in Parkinson’s syndrome: an unmet need underpinned by real life clinical tests

Frontiers in Neurology, Год журнала: 2023, Номер 14

Опубликована: Май 25, 2023

We have recently published the notion of “vitals” Parkinson’s, a conglomeration signs and symptoms, largely nonmotor, that must not be missed yet often considered in neurological consultations, with considerable societal personal detrimental consequences. This “dashboard,” termed Chaudhuri’s vitals are summarized as 5 key vital symptoms or comprise (a) motor, (b) (c) visual, gut, oral health, (d) bone health falls, finally (e) comorbidities, comedication, dopamine agonist side effects, such impulse control disorders. Additionally, addressing also may reflect inadequate management strategies, leading to worsening quality life diminished wellness, new concept for people Parkinson’s. In this paper, we discuss possible, simple use, clinically relevant tests can used monitor status these vitals, so incorporated into clinical practice. use term Parkinson’s syndrome describe disease, “disease” is now abandoned many countries, U.K., reflecting heterogeneity which by syndrome.

Язык: Английский

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An examination of three prescribing cascades in a cohort of older adults with dementia

BMC Geriatrics, Год журнала: 2021, Номер 21(1)

Опубликована: Май 8, 2021

Abstract Background Prescribing cascades are a source of inappropriate prescribing for older adults with dementia. We aimed to study three in Nova Scotians dementia using administrative databases. Methods Cohort entry Scotia Seniors’ Pharmacare Program beneficiaries was the date diagnosis. Prescription drug dispensing data extracted inciting medication and second treatment (cholinesterase inhibitor bladder anticholinergic, metoclopramide Parkinson’s disease medication, or calcium channel blocker (CCB) diuretic) over six-year period April 1, 2009 March 31, 2015. In separate analyses, an signaled look back 365 days from first confirm that started after medication. The cascade considered when within 180 treatment. Sex differences were tested t-tests chi square tests as appropriate. Both univariate (unadjusted) multivariate (adjusted) logistic regression (adjusted age, rurality, sex) Cox proportional hazards used identify risk factors cascade. Results From 2005 2015, 28,953 Seniors' (NSSPBD) identified. There 60 cases anticholinergics following cholinesterase inhibitors, 11 metoclopramide, 289 diuretic CCB cohort. Regression analysis demonstrated inhibitors diuretics CCBs associated female sex. suggested less often by those on did not use leading more frequently use. Conclusions combination most common common. However, exposure medications increase treatments. Combinations women raising concern may be at increased these cascades.

Язык: Английский

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Prescribing cascades in community‐dwelling adults: A systematic review

Pharmacology Research & Perspectives, Год журнала: 2022, Номер 10(5)

Опубликована: Сен. 19, 2022

Abstract The misattribution of an adverse drug reaction (ADR) as a symptom or illness can lead to the prescribing additional medication, referred cascade. aim this systematic review is identify published cascades in community‐dwelling adults. A was reported line with PRISMA guidelines and pre‐registered PROSPERO. Electronic databases (Medline [Ovid], EMBASE, PsycINFO, CINAHL, Cochrane Library) grey literature sources were searched. Inclusion criteria: adults; risk‐prescription medication; outcomes‐initiation new medicine “treat” reduce ADR risk; study type‐cohort, cross‐sectional, case‐control, case‐series studies. Title/abstract screening, full‐text data extraction, methodological quality assessment conducted independently duplicate. narrative synthesis conducted. total 101 studies (reported 103 publications) included. Study sample sizes ranged from 126 11 593 989 participants 15 examined older adults specifically (≥60 years). Seventy‐eight potential cascade including calcium channel blockers loop diuretic ( n = 5), amiodarone levothyroxine inhaled corticosteroid topical antifungal 4), antipsychotic anti‐Parkinson acetylcholinesterase inhibitor urinary incontinence drugs 4). Identified occurred within three months one year following initial medication. Methodological varied across included Prescribing occur for broad range medications. ADRs should be differential diagnosis patients presenting symptoms, particularly those who started medication preceding 12 months.

Язык: Английский

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Drug interactions for elderly people with mental and behavioral disorders: a systematic scoping review

Archives of Gerontology and Geriatrics, Год журнала: 2020, Номер 93, С. 104283 - 104283

Опубликована: Ноя. 7, 2020

Язык: Английский

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The Prevalence and Characteristics of Psychotropic-Related Hospitalizations in Older People: A Systematic Review and Meta-Analysis

Journal of the American Medical Directors Association, Год журнала: 2021, Номер 22(6), С. 1206 - 1214.e5

Опубликована: Фев. 3, 2021

Язык: Английский

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Cumulative Anticholinergic Burden and its Predictors among Older Adults with Alzheimer’s Disease Initiating Cholinesterase Inhibitors

Drugs & Aging, Год журнала: 2024, Номер 41(4), С. 339 - 355

Опубликована: Март 11, 2024

Язык: Английский

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Changes in Polypharmacy and Psychotropic Medication Use After Diagnosis of Major Neurocognitive Disorders

Alzheimer Disease & Associated Disorders, Год журнала: 2022, Номер 36(3), С. 222 - 229

Опубликована: Июнь 1, 2022

Background: Older adults with major neurocognitive disorder (MNCD) are often exposed to polypharmacy. We aimed assess the prescribing and discontinuation patterns of medications following diagnosis MNCD among community-dwelling older adults. Methods: Using Quebec Integrated Chronic Disease Surveillance System, we conducted a population-based cohort study comparing 1-year prediagnosis postdiagnosis use between group individuals than 65 years newly diagnosed in 2016-2017 control without MNCD. The difference-in-difference method was used estimate variation number prescribed proportion psychotropic anticholinergic medication users. Results: In group, mean (excluding Alzheimer disease treatments) increased by 1.25 year after diagnosis. respective increase 0.45 yielding an adjusted difference-in-differences 0.81 (95% confidence interval: 0.74; 0.87) groups. proportions antipsychotic, antidepressant, users 13.2% (12.5; 13.9), 7.1% (6.5; 7.7), 3.8% (3.1; 4.6), respectively. Conclusions: burden tends antipsychotics antidepressants may explain part observed increase.

Язык: Английский

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Resident-Level Predictors of Dementia Pharmacotherapy at Long-Term Care Admission: The Impact of Different Drug Reimbursement Policies in Ontario and Saskatchewan: Prédicteurs de la pharmacothérapie de la démence au niveau des résidents lors de l’hospitalisation dans des soins de longue durée : l’impact de différentes politiques de remboursement des médicaments en Ontario et en Saskatchewan

The Canadian Journal of Psychiatry, Год журнала: 2020, Номер 65(11), С. 790 - 801

Опубликована: Апрель 10, 2020

Cholinesterase inhibitors (ChEIs) and memantine are approved for Alzheimer disease in Canada. Regional drug reimbursement policies associated with cross-provincial variation ChEI use, but it is unclear how these influence predictors of use. Using standardized data from two provinces differing policies, we compared resident-level characteristics dementia pharmacotherapy at long-term care (LTC) admission.Using linked clinical administrative databases, examined use among residents and/or significant cognitive impairment admitted to LTC facilities Saskatchewan (more restrictive policies; n = 10,599) Ontario (less restrictive; 93,331) between April 1, 2009, March 31, 2015. Multivariable logistic regression models were utilized assess resident demographic, functional, pharmacotherapy.On admission, 8.1% receiving 33.2% Ontario. In both provinces, severe impairment, aggressive behaviors, recent antipsychotic more likely receive pharmacotherapy; while those who unmarried, later years, had a greater degree frailty, hospitalizations less likely. The direction the association older age, rural residency, medication number, anticholinergic therapy differed provinces.While criteria coverage resulted fewer entering on pharmacotherapy, there relatively few differences factors across provinces. Longitudinal studies needed prevalence impact patient outcomes.

Язык: Английский

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An examination of three prescribing cascades in a cohort of older adults with dementia

Research Square (Research Square), Год журнала: 2021, Номер unknown

Опубликована: Фев. 11, 2021

Abstract Background Prescribing cascades are a source of inappropriate prescribing for older adults with dementia. We aimed to study three in Nova Scotians dementia using administrative databases. Methods Cohort entry Scotia Seniors’ Pharmacare Program beneficiaries was at the date diagnosis. Prescription drug dispensation data extracted inciting medication and second treatment (cholinesterase inhibitor bladder anticholinergic, metoclopramide Parkinson’s disease medication, or calcium channel blocker (CCB) diuretic) over six-year period from April 1, 2009 March 31, 2015. In separate analyses, an signaled look back 365 days first confirm that started after medication. The cascade considered when within 180 treatment. Sex differences were tested t-tests chi square tests as appropriate. Both univariate (unadjusted) multivariate (adjusted) logistic regression (adjusted age, rurality, sex) Cox proportional hazards used identify risk factors cascade. Results 2005 2018 28,953 Seniors (NSSPBD) identified. There 60 cases anticholinergics following cholinesterase inhibitors, 11 metoclopramide, 289 diuretic CCB. Regression analysis demonstrated inhibitors diuretics CCBs associated female sex. analyses suggested less often by those on but did not CCB use leading more frequently use. Conclusions Of investigated, most common common. these women suggesting clinicians need increased attention monitor among women.

Язык: Английский

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