The Potential Emergence of Disease-Modifying Treatments for Alzheimer Disease: The Role of Primary Care in Managing the Patient Journey

Abstract

Despite recent setbacks, disease-modifying treatments (DMTs) for Alzheimer disease (AD) might become available within a few years. These DMTs are likely to be used in the early stages of AD to avoid the progression to manifest dementia, which implies that a large reservoir of prevalent cases would need to be evaluated when DMTs first become available. Primary care providers (PCPs) would play a vital role in managing the patient flow to specialty care. We review the literature on diagnostic tests that could be used by PCPs and estimate the impact of different testing approaches on demand for specialty care. While many tests have been evaluated, only the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) perform acceptably for detection of early-stage cognitive decline with sensitivities and specificities of 55% to 82% and 72% to 84%, respectively, for the MMSE; and 77% to 96% and 73% to 95%, respectively, for the MoCA. However, neither test is sufficiently specific for the AD pathology and would result in 4 to 5 false positives for each true positive. Blood-based tests for AD biomarkers may soon become available for clinical use. A plasma amyloid-␤ (A␤) test has been shown to have a sensitivity of up to 97% and specificity of up to 81%. Adding this test to the MMSE or MoCA could reduce false positives by approximately 80%. These findings suggest a combination of brief cognitive tests and blood-based biomarker tests will allow PCPs to identify patients with potential early stage AD efficiently and triage them for further evaluation. (J Am Board Fam Med 2019;32:931-940.)

Blood‐based biomarkers for Alzheimer's pathology and the diagnostic process for a disease‐modifying treatment: Projecting the impact on the cost and wait times

“…Limited capacity of dementia specialists is not only the most relevant obstacle to access to a possible disease‐modifying treatment, but it also the most difficult to address because of long training times for specialists and overall increasing demand for geriatric care because of other age‐related conditions in an aging population. In response, several authors have called for greater involvement of primary care providers in the evaluation process 3,27,28 . Primary care–led memory services models have been introduced that could germinate such task shifting 29–31 However, it is not clear that those models, which currently focus on support for dementia patients and coordination with social services, are equipped to handle the medicalized nature of services around a disease‐modifying treatment.…”

“…A recent review evaluated tools to identify early stage AD at the primary care level. The findings suggest that brief cognitive tests, such as the Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), are reasonably accurate for the detection of mild cognitive impairment (MCI) but are not designed to distinguish the underlying etiology 3,4 . Although several tests for the pathologic hallmarks of AD, which are suitable for primary care settings, are being developed, only plasma‐based biomarker tests currently have sufficient evidence to likely enter routine clinical practice in the foreseeable future 5,6 …”

Exploring Sphingolipid Implications in Neurodegeneration

“…Despite significant efforts undertaken by the international community, precise mechanism of the development of AD still remains unknown. In contrast to other cognitive pathologies causing clinical signs of dementia, the cardinal pathologic features of AD are amyloid beta (Aβ) aggregates, the major components of senile plaques, and neurofibrillary tangles of τ protein (22). It has been shown that amyloidogenesis plays a key role in induction and development of AD (23).…”

New Research on Back Pain, Diet and Diabetes, Advanced Care Planning, and Other Issues Frequently Seen in Family Medicine

“…As pharmacy providers directly interact with a large number of patients every day, and more often than the individual's primary care clinician, there are multiple ways in which community pharmacists can contribute to suicide screening, education, and prevention. Lam et al 8 provide an update on the status of Alzheimer disease detection and treatment. A combination of brief cognitive tests and blood-based biomarker tests may soon allow primary care providers to identify patients with early-stage Alzheimer disease (AD) efficiently and triage them for further evaluation or treatment.…”