Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer's disease (MCI and dementia) in primary care: a review and synthesis

Abstract

The critical role of primary care clinicians (PCCs) in Alzheimer's disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early signs of cognitive deficits (i.e. MCI due to AD and mild AD dementia). A timely AD diagnosis is particularly important for optimizing patient care and enabling the appropriate use of anticipated DMTs. An accelerating challenge for PCCs and AD specialists will be to respond to innovations in diagnostics and therapy for AD in a system that is not currently well positioned to do so. To overcome these challenges, PCCs and AD specialists must collaborate closely to navigate and optimize dynamically evolving AD care in the face of new opportunities. In the spirit of this collaboration, we summarize here some prominent and influential models that inform our current understanding of AD. We also advocate for timely and accurate (i.e. biomarker-defined) diagnosis of early AD. In doing so, we consider evolving issues related to prevention, detecting emerging cognitive impairment and the role of biomarkers in the clinic.

Keywords: Alzheimer disease; biomarkers; dementia; disease-modifying therapies; mild cognitive impairment; primary health care.

Fig. 1

(a) Dynamic biomarkers of the AD pathological cascade model. (b) Hypothetical model of the pathologic–clinical continuum of AD. AB, amyloid‐beta; AD, Alzheimer’s disease; CSF, cerebrospinal fluid; FDG, fluorodeoxyglucose; MCI, mild cognitive impairment; MRI, magnetic resonance imaging; PET, positron emission tomography. (a) reprinted from The Lancet Neurology, Vol. 12, Jack CR Jr et al, Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers, 207–216, ©2013, with permission from Elsevier [15]. (b) adapted from Sperling et al. [16]

Fig. 2

A pathway for monitoring and evaluating individuals at risk of cognitive impairment. This pathway suggests a standard workup to evaluate cognitive impairment and also includes groupings of specific tests into those that are focused on detecting cognitive impairment/dementia due to AD versus those that are less specific but that still help identify a differential diagnosis for other causes of cognitive impairment/dementia. It is important to recognize that this decision tree does not offer staging for AD. As DMTs become available, staging will become more relevant, as these drugs will likely be FDA‐indicated based on stage. Aβ, amyloid‐beta; AD, Alzheimer’s disease; AD8, Ascertain Dementia 8‐Item Informant Questionnaire; AQ, Alzheimer’s Questionnaire; CT, computed tomography; FDG, fluorodeoxyglucose; MCI, mild cognitive impairment; MIS, Memory Impairment Screen; MOCA, Montreal Cognitive Assessment; MRI, magnetic resonance imaging; PET, positron emission tomography; TFT, thyroid function test