Hwinei J Tavengwa
DEMENTIA MEDICATION and COPD
Dementia is a loss of brain function that affects ability to carry out daily activities. It usually
occurs in older age and affects thinking, judgment, memory and behavior. The current
pharmacologic treatment of dementia includes the use of cholinesterase inhibitors such as
donepezil, rivastigmine, and galantamine. While these have been successful in the management
of dementia, cautious administration has been suggested in patients with COPDi. Cholinesterase
inhibitors have cholinergic effects that include increasing secretions in the respiratory tract, and
thus exacerbate chronic obstructive pulmonary disease (COPD)ii. A few studies have directly
probed the effects of dementia medication on COPD. In their cohort study, Stephenson A &
others concluded that there was no significant difference in adverse pulmonary events between
new users of cholinesterase inhibitors and non users, in patients with dementiaiii. Other studies
have looked at the effects of cholinesterase inhibitors on COPD in patients without dementia.
Long term exposure to cholinesterase inhibitor agricultural pesticides was associated with
reduction in lung function and higher incidences of COPD in agricultural workers in India iv.
Since there is limited conclusive data on the effects of dementia medications on COPD, and yet a
significant patient population with both dementia and COPD, we are interested in studying the
effects of dementia medications such as cholinesterase inhibitors on COPD.
Hwinei J Tavengwa
DEMENTIA MEDICATION and COPD
i
Bonner, L. T. and E. R. Peskind (2002). "Pharmacologic treatments of dementia." Medical Clinics of North
America 86(3): 657-674.
The management of dementia patients encompasses pharmacologic, behavioral, and psychosocial
intervention strategies. Before pharmacologic intervention is instituted, it is important that sources of excess
disability and comorbidity be eliminated or reduced. Identification of comorbid medical and psychiatric conditions,
such as depression and delirium, should be identified and appropriately treated. Providing caregivers with education,
support, and practical advice is a critical component of the management of the demented patient. The current
standard of care for pharmacologic management of the cognitive and functional disabilities of AD consists of the
combination of a cholinesterase inhibitor and high-dose vitamin E. This standard is based on the results of largescale, double-blind, placebo-controlled trials. Cholinesterase inhibitors are the only FDA-approved pharmacologic
treatments for AD. Cholinesterase inhibitors have been shown to be effective in the treatment of the cognitive,
behavioral, and functional deficits of AD. Large-scale placebo-controlled trials of tacrine, donepezil, rivastigmine,
and galantamine have demonstrated moderate benefits in patients with mild to moderate AD. Donepezil,
rivastigmine, and galantamine are the first-line choices in the treatment of AD because of their lack of
hepatotoxicity, ease of administration, few significant drug-drug interactions, and mild to moderate side effects.
There are few contraindications to the use of cholinesterase inhibitors. Known hypersensitivity to a specific drug or
its derivatives is the only true contraindication. Cautious administration of cholinesterase inhibitors is advised in
patients who have a previous history of allergy or adverse reactions to prior cholinesterase inhibitors, severe liver
disease, preexisting bradycardia, peptic ulcer disease, current alcoholism, asthma, or chronic obstructive pulmonary
disease. Nausea, vomiting, diarrhea, and anorexia are the most common side effects of cholinesterase inhibitors.
These gastrointestinal side effects can be minimized by gradual dose increases, administration with food, adequate
hydration, and judicious use of an antiemetic. Vitamin E has been demonstrated to slow the progression of AD in
several small and one large placebo-controlled trials. Because of its low cost and safety, it is recommended in
addition to a cholinesterase inhibitor for the treatment of AD. There are no FDA-approved treatments for DLB and
VaD. One small placebo-controlled trial demonstrated that rivastigmine may be effective in the treatment of DLB.
More large-scale placebo-controlled trials are needed to confirm the results of this study. Treatment of VaD focuses
on the control, identification, and management of cerebrovascular disease and vascular risk factors. Although there
are no peer-reviewed reports on the efficacy of cholinesterase inhibitors for VaD or mixed AD/VaD, early reports
suggest that these agents may also be effective for mixed AD/VaD. The indications for the use of cholinesterase
inhibitor drugs are eventually likely to broaden to include DLB, mixed AD/VaD, and AD in its more advanced
stages.
ii
Herrmann, N. (2002). "Cognitive pharmacotherapy of Alzheimer's disease and other dementias."
Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie 47(8): 715-722.
OBJECTIVE: The objective of this paper is to review the randomized controlled trials (RCTs) on
the pharmacotherapy of Alzheimer's disease and other dementias and to provide evidence-based
recommendations for treatment of the cognitive impairment associated with these disorders. METHOD:
A Medline search was conducted for RCTs, using the following key words: Alzheimer's disease,
dementia, therapy, cholinesterase inhibitor, donepezil, rivastigmine, and galantamine. Studies were
critically appraised, followed by a review of published major clinical practice guidelines.
Recommendations for treatment were made based on best available evidence. RESULTS: The
pharmacotherapy of Alzheimer's disease should include the meticulous management of vascular risk
factors (for example, hypertension, diabetes, cholesterol, and stroke prophylaxis) and consideration for
supplementation with folate, vitamin B complex, and vitamin E. Patients should be offered at least 1 trial
of a cholinesterase inhibitor, with the possibility of another trial if the first is poorly tolerated or
ineffective. Patients with vascular dementia and dementia with Lewy bodies should also be offered
treatment with cholinesterase inhibitors. At this time, we lack sufficient data to recommend the use of
hormone replacement or antiinflammatory therapy for treatment of dementia as the primary indication.
CONCLUSION: Reasonable evidence exists to provide recommendations for the pharmacotherapy of
dementia. Treatment will likely result in modest but important benefits to patients, caregivers, and
society.
Hwinei J Tavengwa
DEMENTIA MEDICATION and COPD
iii
Stephenson, A., D. P. Seitz, et al. (2012). "Cholinesterase inhibitors and adverse pulmonary events in older people
with chronic obstructive pulmonary disease and concomitant dementia: a population-based, cohort study." Drugs
and Aging 29(3): 213-223.
BACKGROUND: Cholinesterase inhibitors (ChEIs) are a mainstay treatment for individuals with
dementia. ChEIs may worsen airflow obstruction because of their pro-cholinergic properties. OBJECTIVE: The
objective of this study was to evaluate the risk of serious pulmonary complications in the elderly with concomitant
chronic obstructive pulmonary disease (COPD) and dementia who were receiving ChEIs. METHODS: This was a
population-based, cohort study conducted between 2003 and 2010 in residents of Ontario, Canada. Subjects were
over the age of 66 years and had concomitant dementia and COPD, identified using linked administrative databases.
Exposure to ChEIs was determined using a drug benefits database. The primary outcome was an emergency room
(ER) visit or hospitalization for COPD. The risk difference at 60 days and the relative risk (RR) for study outcomes
were estimated in the propensity score-matched sample. RESULTS: Of 266,840 individuals with COPD, 45,503 had
a concomitant diagnosis of dementia. A total of 7166 unexposed subjects were matched to subjects newly exposed
to ChEIs. New users of ChEIs were not at significantly higher risk of ER visits or hospitalizations for COPD (RR
0.90; 95% CI 0.76, 1.07) or COPD exacerbations (RR 1.02; 95% CI 0.91, 1.15). Furthermore, ER visits for any
respiratory diagnoses were not increased among new users of ChEIs (RR 1.02; 95% CI 0.87, 1.19) when compared
with non-users. Sub-group analyses were consistent with the main analysis. CONCLUSIONS: In a large cohort of
elderly individuals with COPD and dementia, new users of ChEIs had a similar risk for adverse pulmonary
outcomes as those who were not receiving ChEIs.
iv
Chakraborty, S., S. Mukherjee, et al. (2009). "Chronic exposures to cholinesterase-inhibiting pesticides adversely
affect respiratory health of agricultural workers in India." J Occup Health 51(6): 488-497.
OBJECTIVE: The impact of long term exposure to cholinesterase (ChE)-inhibiting organophosphate (OP)
and carbamate (C) pesticides on the respiratory health of agricultural workers in India was investigated.
METHODS: Three hundred and seventy-six nonsmoking agricultural workers (median age 41 yr) from eastern India
who sprayed OP and C pesticides in the field and 348 age- and sex-matched control subjects with non-agricultural
occupations from the same locality were enrolled. Prevalence of respiratory symptoms was obtained by
questionnaire survey, and pulmonary function tests were carried out by spirometry. Chronic obstructive pulmonary
disease (COPD) was diagnosed by the Global Obstructive Lung Disease (GOLD) criteria, and erythrocyte
acetylcholinesterase (AChE) was measured by the Ellman method. RESULTS: Agricultural workers had greater
prevalences of upper and lower respiratory symptoms, and appreciable reduction in spirometric measurements.
Overall, lung function reduction was noted in 48.9% of agricultural workers compared with 22.7% of control, and a
restrictive type of deficit was predominant. COPD was diagnosed in 10.9% of agricultural workers compared with
3.4% of controls (p<0.05 in chi(2) test), and the severity of the disease was greater in agricultural workers. Red
blood cell (RBC) AChE was lowered by 34.2% in agricultural workers, and the fall in AChE level was positively
associated with respiratory symptoms, lung function decrement and COPD after controlling for education and
income as potential confounders. CONCLUSIONS: Long-term exposure to cholinesterase-inhibiting agricultural
pesticides currently in use in India is associated with a reduction in lung function, COPD and a rise in respiratory
symptoms.