This document discusses drugs used in the management of dementias. It notes that treatment is largely supportive, but cholinesterase inhibitors can sometimes improve cognitive function for conditions like Alzheimer's disease. The most common types of dementia are described. Acetylcholinesterase inhibitors and memantine are discussed as medications that can improve cognitive symptoms, while antipsychotics and antidepressants may help manage behavioral symptoms. Adverse effects of these drugs are also summarized.

1. DRUGS USED IN THE MANAGEMENT OF
DEMENTIAS
NEUROPHARMACOLOGY
[S. N. KANYIMBA]

2. Introduction
Dementia is chronic, global, usually irreversible deterioration of cognition
For most causes of dementia, treatment is largely supportive. Cholinesterase inhibitors
can sometimes temporarily improve cognitive function.
Dementia may occur at any age but affects primarily the elderly
The most common types of dementia are
• Alzheimer disease (most common cause of dementia)
• Vascular dementia
• Lewy body dementia
• Frontotemporal dementias
• HIV-associated dementia
Dementia also occurs in patients with Parkinson disease, Huntington disease,
progressive supranuclear palsy, Creutzfeldt-Jakob disease and neurosyphilis. Patients
can have > 1 type (mixed dementia).
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3. Management of dementia
• Treatment is largely supportive for most causes
• Currently, no medications have been shown to prevent or cure dementia
• Medications may be used to treat the behavioural and cognitive
symptoms but have no effect on the underlying disease process
• Acetylcholinesterase inhibitors: useful for Alzheimer disease and dementia
in Parkinson's disease and vascular dementia
• Memantine (an N-methyl-D-aspartate (NMDA) receptor blockers): may be
of benefit. Due to their differing mechanisms of action, memantine and
acetylcholinesterase inhibitors, they can be used in combination for
increased benefit.
• Antipsychotic drugs: to control behaviour disorders such as aggression
• Antidepressant drugs: for patients with signs of depression (avoid
antidepressants that have anti-muscarinic effects; thus SSRIs are
preferred)
• Avoid sedatives (such as benzodiazepines) and drugs with anti-muscarinic
activity: they worsen the cognitive impairment
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4. Drugs used to improve cognitive function in dementias
CNS acting cholinesterase inhibitors (ChEIs)
• Include donezepil, rivastigmine, galantamine and tacrine
• MOA: inhibit cholinesterase thereby increasing the acetylcholine levels in
the brain. Acetylcholine is involved in information processing in the
cerebral cortex.
• Modestly improve cognitive function
• All ChEIs are equally effective, but tacrine is rarely used because of
hepatotoxicity
• Adverse effects: The most common adverse effects are GI (e.g. nausea and
diarrhea). Dizziness, bradycardia, syncope and cardiac arrhythmias can
occur. The adverse effects are dose related. Treatment is initiated with
lower doses that are titrated upwards till the desired benefits are achieved
or when intolerable adverse effects occur.
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5. Drugs used to improve cognitive function in
dementias …. cont’d
Memantine
• Memantine is an NMDA (N-methyl-d-aspartate) antagonist
(inhibits glutamate)
• Blockade of NMDA receptors by memantine slows the
intracellular calcium accumulation and thereby helps
prevent further neuronal damage
• Slows the loss of cognitive function in patients with
moderate to severe dementia and may be synergistic when
used with a cholinesterase inhibitor
• Adverse effects: dizziness, headache and confusion
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6. Alzheimer’s disease (AD)
Alzheimer disease causes progressive cognitive deterioration
It is characterized by β-amyloid deposits and neurofibrillary tangles in the
cerebral cortex and subcortical gray matter.
Pathophysiology
Typically, extracellular β-amyloid deposits, intracellular neurofibrillary tangles
(paired helical filaments), and senile plaques develop, and neurons are lost.
Cerebrocortical atrophy occurs and use of cerebral glucose is reduced.
Perfusion in the parietal lobe, temporal cortices and prefrontal cortex is
reduced.
Other common abnormalities include increased brain and CSF concentrations
of the tau protein (a component of neurofibrillary tangles and β-amyloid) and
reduced levels of choline acetyltransferase and various neurotransmitters
(e.g. somatostatin)
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7. Management of AD
• Management of AD is generally similar to that of other dementias
• General supportive treatment is the same as that of all dementias
• The standard medical treatment for AD includes cholinesterase
inhibitors and memantine (N-methyl-D-aspartate (NMDA)
antagonist)
• Efficacy of high-dose vitamin E, selegiline, NSAIDs, Ginkgo biloba
extracts and statins is unclear
• The following classes of psychotropic medications have been used
to treat the secondary symptoms of AD, such as depression,
agitation, aggression, hallucinations, delusions, and sleep disorders:
antidepressants, anxiolytics, neuroleptics, beta-blockers and anti-
epileptic drugs
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8. ENDE