A New Framework for Dementia Nomenclature

Abstract

ImportanceNomenclature in the field of neurodegenerative diseases presents a challenging problem. Inconsistent use of terms such as Alzheimer disease and dementia has compromised progress in clinical care, research, and development of therapeutics. Dementia-associated stigma further contributes to inconsistent and imprecise language. The result is a lack of clarity that produces confusion with patients and the general public and presents communication challenges among researchers. Therefore, the Advisory Council on Research, Care, and Services of the National Plan to Address Alzheimer’s Disease authorized a committee to make recommendations for improvement.ObjectiveTo establish a systematic neurodegenerative disease framework for information collection and communication to standardize language usage for research, clinical, and public health purposes.Evidence ReviewThe Dementia Nomenclature Initiative organized into 3 major stakeholder working groups: clinicians, researchers, and the public (including individuals living with dementia and family caregivers). To inform the work, the initiative completed a narrative literature review of dementia nomenclature evolution over the last century across the PubMed, CINAHL, PsycInfo, and Scopus databases (January 1, 2000, through July 31, 2020). Initiative working groups used the results as a foundation for understanding current challenges with dementia nomenclature and implications for research, clinical practice, and public understanding. The initiative obtained additional input via focus groups with individuals living with dementia and caregivers, with separate groups for race and ethnicity (American Indian or Alaska Native, Asian or Pacific Islander, Black or African American, Hispanic or Latino, and White) as an initial assessment of the meaning of dementia-related terms to these groups.FindingsFrom working group deliberations, the literature review, and focus group input, the initiative developed a framework clearly separating the clinical syndromic presentation experienced by affected individuals from possible underlying pathophysiologies. In the framework, domains of clinical impairment, such as cognitive, behavioral, motor, and other neurologic features, are graded by level of impairment between none and severe. Next, biomarker information describes underlying disease processes, explains the syndrome, and identifies possible disease labels: Alzheimer disease, frontotemporal degeneration, dementia with Lewy bodies, or vascular cognitive impairment dementia.Conclusions and RelevanceThe Dementia Nomenclature Initiative established a framework to guide communication about cognitive impairment among older adults. Wider testing and refinement of the framework will subsequently improve the information used in communicating about cognitive impairment and the way in which the information is used in clinical, research, and public settings.

Clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome

“…To put this work in contexts, recent work on terminology would characterize LANS as a subtype of amnestic MCI or amnestic dementia. 34 , 35 The addition of preservation of neocortical functions, older age at symptom onset, mild clinical severity and semantic memory impairment would make these amnestic syndromes more likely to be LANS and the additional imaging would localize the syndromes to the limbic system. These refinements would add greater specificity to the diagnosis for clinicians.…”

“…In the absence of one-to-one mapping with a single underlying pathology and lack of clinically applicable in vivo biomarker of TDP-43, LANS can be framed as a clinico-radiological, or neurologic, entity rather than clinicopathologic. 34 , 35 While the current investigation focuses on LANS associations with LATE-NC, data on other neuropathologies are provided in Supplementary material . The LANS criteria include core, standard and advanced criteria that can be measured in vivo along with levels of certainty that clinical symptoms are caused by the predominant degeneration of the limbic system (described in Box 1 ).…”

A limbic-predominant amnestic neurodegenerative syndrome associated with TDP-43 pathology

“…To put this work in another clinical context, recent work on terminology would characterize LANS as a subtype of amnestic MCI or amnestic dementia(34). The addition of preservation of neocortical functions, older age at symptom onset, mild clinical severity and semantic memory impairment would make these amnestic syndromes more likely to be LANS and the additional imaging would localize the syndromes to the limbic system.…”

“…While the definition of LANS is agnostic to molecular pathology, this syndrome is highly associated with LATE-NC but also other less common neuropathologic entities selectively targeting the limbic system, for instance limbic-predominant forms of Alzheimer’s disease or argyrophilic grain disease (AGD). Given that LANS does not perfectly map onto a single underlying pathology and that there is currently no clinically applicable in vivo biomarker of TDP-43, it does not meet the definition of a clinicopathologic entity(34). If an accepted TDP-43 biomarker is developed it could be combined with LANS to define a clinicopathologic entity like LATE.…”

Pathologic and cognitive correlates of plasma biomarkers in neurodegenerative disease

“…First, we tested diagnostic accuracy and pathological correlates of plasma biomarkers by disease stage: in NormCog (part 1) and ImpCog (part 2). Consistent with the framework proposed by the Dementia Nomenclature Initiative, 23 motivated by the imperfect mapping of clinical syndrome with pathology, we define cases by syndrome and use plasma biomarkers to link to underlying pathoetiology. We confirmed Aβ status of participants using autopsy, cerebrospinal fluid (CSF), or 18 F-florbetaben positron emission tomography (PET).…”