Genetic Testing

The Genome-Wide Association Study has identified a number of regions in the genome that may be associated with increased risk for late-onset AD. Researchers have confirmed 33 regions of interest in the AD genome.7 Genetic testing for APOE ε4 is available in both consumer or commercial markets.7 It should be recognized, however, that genetic testing establishes only a component of an individual’s risk profile and must be used judiciously, with the recognition that environment, lifestyle, family medical history, and other genetic factors also will play a role in the development of AD.7

Imaging Studies

It is beneficial to perform brain imaging to rule out other organic causes for dementia, such as vascular disease or a tumor. A computed tomography (CT) scan provides images of the brain in greater detail than radiographs and can assist in identifying a brain injury, tumor, stroke, or other contributor to dementia symptoms.19  Magnetic resonance imaging is used clinically and in research to produce images of brain structures and identify abnormal changes such as cerebral atrophy.19 Signs of atrophy may further support a diagnosis of AD or other neurodegenerative condition but on their own cannot establish a specific diagnosis.19 

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Research shows that patients with dementia often will exhibit abnormal levels of glucose uptake in specific brain regions.19 An FDG PET scan can identify this type of pattern and facilitate diagnosis of the underlying cause of the dementia.19

Amyloid PET scans measure beta-amyloid deposits. High levels of beta-amyloid are associated with amyloid plaques present in AD.19 In addition, a number of tracers can be used with amyloid PET scans to provide diagnostic assistance when AD is suspected but not clearly established by comprehensive assessment.19  This type of imaging also may be helpful in diagnosing dementia in individuals with mild or unusual symptoms, onset at an early age, or other conditions (eg, severe depression) that could contribute to their symptoms.19,20 Conversely, a negative amyloid PET scan can help rule out AD.19,20

Tau PET scans identify abnormal deposition of tau (NFTs).19 There are multiple tau tracers that have been used in research studies to determine their usefulness in clinical practice.19 Research findings support using amyloid and tau PET scans to identify individuals at greatest risk for developing AD.19 This imaging type also has been helpful in selecting clinical trial participants and in evaluating the effect of experimental drugs designed to modify amyloid or tau pathways.19

The Future of Biomarkers

Throughout the past 10 years, advances in biomarkers have allowed for the identification of AD-related changes in the brains of living patients. This is incredible progress because, historically, brain changes could only be studied postmortem.  In addition, this has allowed researchers to monitor the disease’s onset, follow its progression, and test promising medications and treatments.19-21 Researchers hope to build on these successes and to advance biomarker research by:

  • Developing a full complement of biomarkers, specifically those that are less expensive and less invasive, and to evaluate medications to diagnose, prevent, and treat AD
  • Advancing innovative PET imaging and biomarkers to identify distinctive AD-related brain changes.
  • Using state-of-the-art MRI methodology to measure brain structure, function, and connections
  • Helping to identify and monitor early-stage disease by developing and refining more sensitive clinical and neuropsychological assessments.19-21

Treatment Modalities

 Lifestyle Interventions

Although lifestyle interventions may not be considered true emerging therapies, the findings of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) — the world’s first large multidimensional study of lifestyle interventions — are worth noting. FINGER documented that at least a third of AD is determined by modifiable factors.22 There were 4 intervention components in this study: nutritional guidance; physical exercise; cognitive training and social activity; and intensive monitoring and management of metabolic and vascular risk.22 All these components were found to have a profound impact on the progression of dementia in the study.

Cognitive Therapy

Psychosocial treatment modalities focus on cognitive stimulation therapy and cognitive remediation and their ability to successfully preserve cognitive function in people with mild to moderate dementia.22 Cognitive stimulation therapy (CST) is a themed activity program implemented during several weeks in small groups led by a trained nurse, occupational therapist, or caregiver. These sessions are structured with activities found to be most beneficial. They include a warm-up activity, a “reality orientation board,” discussion of current news stories, word puzzles, and a practical activity such as baking.22 These programs have been found to enhance the memory and critical thinking skills of people with mild to moderate dementia and to improve their quality of life.22

Cognitive remediation is similar to CST but includes a set of activities that also focuses on learning and exercises designed to improve brain function.22 The associated cognitive training targets cognitive domains most sensitive to aging (episodic memory, executive function, mental speed, and working memory) with a focus on everyday situations.22

Current Therapies

Cholinesterase inhibitors (eg, donepezil, rivastigmine, and galantamine) and the NMDA-receptor antagonist memantine have been used for the treatment of AD. The cholinesterase inhibitors prevent AChE from breaking down acetylcholine.8,19 Memantine blocks the influence of glutamate, which is released disproportionately in the brains of those with AD, causing irreparable damage to brain cells.8,19 Although these medications have not been shown to change the overall course of dementia, they can slow its progression.

Disease modifying therapies (DMT) are interventions that can produce an enduring change in the clinical progression of AD by interfering in the underlying pathophysiologic mechanisms of the disease process.23 When DMTs are approved for widespread use, biomarker testing will be essential to aid in diagnosis and monitoring the effect of treatments.23 In addition, biomarker results will be critical to the initiation and termination of treatment regimens and may help determine whether combination therapies are appropriate at the individual level.8,23

Immunization and Immunotherapy

Immunizations that target proteins other than tau have become an increasingly pursued therapeutic approach.9 The furthest advanced is a beta-amyloid-based active and passive immunization in AD, which, despite some setbacks, has resulted in some promising results.9,24

There are some interesting immunotherapies on the horizon as well, including anti-beta-amyloid antibodies that have been specifically developed to hinder the beta-amyloid cascade.25,26 Preclinical studies have substantiated the use of immunotherapy against AD, which has prompted a series of clinical trials.25,26  Phase 3 trials using monoclonal antibodies against beta-amyloid in patients with mild to moderate AD showed some impact on biomarkers, however, the primary end points were not successfully achieved.25,26 

It has been proposed that administering anti-beta-amyloid immunotherapy at the early presymptomatic stage (secondary prevention) would improve the therapeutic effect.25,26 Once high-risk individuals have be identified using biomarkers, then it would be advantageous for them to begin chronic long-term immunotherapy.25,26 These treatments pose a challenge to healthcare systems, however, because of issues related to antibody production and the costs of such treatments.25,26

Amy Arnold Haney, DMSc, PA-C, is a primary care provider who works with short-term rehabilitation patients, long-term care patients, and hospice patients in Jacksonville, Florida.


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This article originally appeared on Clinical Advisor