Modest evidence has shown steady progress in delaying the progression from mild cognitive impairment to early AD, but no pharmaceutical has yet been shown to prevent the onset and outcomes of the disease.1-5 Therefore, a holistic, health-promoting lifelong lifestyle and a “multimodal neuroprotective and neurorestorative” approach are being tested.6
What’s Been Tried
Treatment of AD has typically concentrated on managing key symptoms, including:
• gradual declines in short-term or episodic memory and functional status;
• disease-related neuropsychiatric behaviors that are potentially deleterious to patients or those around them (depression, agitation, aggression, insomnia, wandering); and
• cognitive impairment ranging from problems with information processing and the executive control functions of planning, organizing and decision-making to symptoms of psychosis, including delusions (usually paranoid in nature) and hallucinations.1,7,8
Cognitive symptoms – the most troublesome for patients with consequences for the other domains – have traditionally been treated with acetylcholinesterase inhibitors such as tacrine, donepezil, rivastigmine and galantamine, as well as memantine, the noncompetitive N-methyl-D-aspartate antagonist – each with “transient symptomatic benefit without modification … of the underlying disease process.”3
Due to its adverse drug reactions, tacrine is seldom used. And no evidence supports the use of statins, vitamin E, ginkgo biloba, melanin, glucocorticoids (prednisone, NSAIDs) or estrogens – with or without progesterone – to prevent or slow AD progression.3,9
What’s Being Tested
Results from in vitro and in vivo preliminary studies suggest new treatments for AD, but findings have not been successfully replicated with humans diagnosed with probable AD.
Efficacy of treatments at the various stages of AD has yet to be demonstrated in large, randomized, controlled trials, or in the complex environments and neurological and social networks of individuals.10
In tandem with symptom management research, efforts continue to concentrate on preventing and treating the neuropathological changes associated with the onset and progression of AD.11 Most research has emphasized reducing beta-amyloid production to prevent amyloid plaque burden, reduce neuroinflammation and reverse disease-related abnormal behaviors.2,5,12
However, AD may have multiple causes (see Table).
On The Horizon
While the exact causal path of AD is not known, its multifactorial nature has prompted the development of novel treatments and multifunction drugs.6,13
Although the discovery of safe, efficacious and well-tolerated vaccines for AD still seems remote.14 Preliminary results of immunizing against self-peptide beta-amyloid are encouraging.15,16
“Agents that interfere with the production of insoluble amyloid fragments in the brain, or accelerate their clearance, are being actively pursued. Despite previous disappointments, it is possible a vaccine may eventually be found.”10
In terms of genetics, “new susceptibility genes for late-onset AD continue to be found with increasing regularity.”10
Nanotechnology (atomic and molecular biochemical engineering) and stem cell technology have seen promising leads in fostering sustained drug delivery across the blood brain barrier to promote neuroregeneration.11
Pharmaceutical Approaches
Some pharmaceutical approaches stand out as possible treatments for AD.
The nonselective antihistamine dimebon, an investigational drug being tested in Russia, seems to improve cognition, functional status, behaviors and global functioning in mild-to-moderate AD, with benefits persisting 1 year after treatment initiation.1
Rosiglitazone, the peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist, improved memory and cognition in mild-to-moderate AD in one study. PPARgamma is a “prototypical ligand-activated nuclear receptor that coordinates lipid, glucose and energy metabolism and is found in elevated levels in the brains of individuals with AD.”2
Intranasal insulin has demonstrated preliminary efficacy in modulating beta-amyloid and improving cognition.17
Lifespan Approach
Large trials are needed to test pharmaceutical treatments with other lifestyle-based approaches that may prove neuroprotective, neurotropic or neurorestorative.6
These approaches include genetics; control of vascular risk factors (systolic hypertension, dyslipidemia); behavioral, cognitively stimulating and environmental enrichment; and over-the-counter possibilities such as antioxidants and vitamin B complex (especially folate), omega-3 polyunsaturated fatty acids, the polyphenol curcumin and other nutraceuticals.10,13,18-23
At least five subgroups of AD exist, and each is probably caused by a different etiopathogenic mechanism. The success of clinical trials and the development of disease-modifying drugs can be furthered by identifying subgroups of AD patients.24
Because risk factors for AD may exist in childhood, research needs to occur across the lifespan. Establishing and maintaining healthy lifestyle habits early is paramount. Examples include restricting dietary saturated fat and high sodium intakes throughout life, avoiding smoking, and engaging in regular physical activity and meaningful social relationships.10, 25-30
Evidence-based algorithms of alternatives tailored to individuals’ age, AD subgroup, stage of AD, cultural/ethnic identification, health status and treatments of comorbidities remain our hope for the future.
References for this article can be accessed at www.advanceweb.com/lpn. Click References on the Magazine toolbar.
Barbara Swanson is an associate professor at Rush University College of Nursing, Chicago.
Popular Theories on Causes of Alzheimer’s Disease2,6,10-12
• Deposition of beta-amyloid peptides resulting in plaque formation
• Oxidative stress
• Tau hyperphosphorylation associated with neurofibrillary tangle formation
• Microglia-mediated neuroinflammatory processes
• Genetic aberrations (e.g., abnormal lipoprotein, apolipoprotein E4)
• Dysregulation of regional brain glucose and lipid metabolism and ionic (calcium, copper, iron) homeostasis
• Neurochemical imbalances including reductions in markers of acetycholine transferase and impairment in neurotransmitter systems (dopamine, glutamate, norepinephrine and serotonin)
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