Alzheimer's Disease Biomarker Decision-Making among Patients with Mild Cognitive Impairment and Their Care Partners.

BACKGROUND: Alzheimer's disease (AD) biomarker tests can be ordered as part of the diagnostic workup of patients with mild cognitive impairment (MCI). Little is known about how patients with MCI and their care partners decide whether to pursue testing. OBJECTIVE: To examine factors that influence AD biomarker testing decisions among patients with MCI and their care partners. DESIGN: We performed structured research interviews with patients with MCI and their study partners to assess the importance of eight factors in the decision whether to undergo AD biomarker testing (6-point Likert scale; 1-extremely unimportant to 6-extremely important): cost, fear of testing procedures, learning if AD is the cause of cognitive problems, concern about health insurance, instructing future planning, informing treatment decisions, family members' opinions, and doctor recommendation. SETTING: Two researchers administered interviews with participants in-person (i.e., participant home, research center) or remotely (i.e., telephone, video-conference). PARTICIPANTS: We completed interviews with 65 patients with a diagnosis of MCI and 57 study partners, referred by dementia specialist clinicians from the University of California, Irvine health system. MEASUREMENTS: We used generalized estimating equations (GEE) to examine the mean importance of each factor among patients and study partners, and the mean difference in importance of each factor within dyads. RESULTS: One third of participants reported the patient had previously undergone AD biomarker testing. Fifty-five percent of patients and 65% of study partners who reported no previous testing indicated a desire for the patient to be tested. GEE analyses found that patients and study partners rated the following factors with highest importance: informing treatment decisions (mean score 5.29, 95% CI: 5.06, 5.52 for patients; mean score 5.56, 95% CI: 5.41, 5.72 for partners); doctor recommendation (4.94, 95% CI: 4.73, 5.15 for patients; 5.16, 95% CI: 4.97, 5.34 for partners); and instructing future planning (4.88, 95% CI: 4.59, 5.16 for patients; 5.11, 95% CI: 4.86, 5.35 for partners). High dyadic agreement was observed for all factors except fear of testing, which patients rated with lower importance than their study partners. CONCLUSIONS: Biomarker testing for AD in patients with MCI is a rapidly evolving practice and limited data exist on patient perspectives. In this study, most patients and their care partners were interested in testing to help inform treatment decisions and to plan for the future. Participants placed high importance on clinician recommendations for biomarker testing, highlighting the need for clear communication and education on the options, limitations, risks, and benefits of testing.

Can MRI Visual Assessment Differentiate the Variants of Primary-Progressive Aphasia?

BACKGROUND AND PURPOSE: Primary-progressive aphasia is a clinically and pathologically heterogeneous condition. Nonfluent, semantic, and logopenic are the currently recognized clinical variants. The recommendations for the classification of primary-progressive aphasia have advocated variant-specific patterns of atrophy. The aims of the present study were to evaluate the sensitivity and specificity of the proposed imaging criteria and to assess the intra- and interrater reporting agreements. MATERIALS AND METHODS: The cohort comprised 51 patients with a root diagnosis of primary-progressive aphasia, 25 patients with typical Alzheimer disease, and 26 matched control participants. Group-level analysis (voxel-based morphometry) confirmed the proposed atrophy patterns for the 3 syndromes. The individual T1-weighted anatomic images were reported by 3 senior neuroradiologists. RESULTS: We observed a dichotomized pattern of high sensitivity (92%) and specificity (93%) for the proposed atrophy pattern of semantic-variant primary-progressive aphasia and low sensitivity (21% for nonfluent-variant primary-progressive aphasia and 43% for logopenic-variant primary-progressive aphasia) but high specificity (91% for nonfluent-variant primary-progressive aphasia and 95% for logopenic-variant primary-progressive aphasia) in other primary-progressive aphasia variants and Alzheimer disease (sensitivity 43%, specificity 92%). MR imaging was least sensitive for the diagnosis of nonfluent-variant primary-progressive aphasia. Intrarater agreement analysis showed mean κ values above the widely accepted threshold of 0.6 (mean, 0.63 ± 0.16). Pair-wise interobserver agreement outcomes, however, were well below this threshold in 5 of the 6 possible interrater contrasts (mean, 0.41 ± 0.09). CONCLUSIONS: While the group-level results were in precise agreement with the recommendations, semantic-variant primary-progressive aphasia was the only subtype for which the proposed recommendations were both sensitive and specific at an individual level.

Primary progressive aphasia: a tale of two syndromes and the rest.

OBJECTIVE: Primary progressive aphasia (PPA) has been proposed to comprise 3 discrete clinical subtypes: semantic, agrammatic/nonfluent, and logopenic. Recent consensus recommendations suggest a diagnostic framework based primarily on clinical and neuropsychological findings to classify these variants. Our objective was to evaluate the extent to which patients with PPA would conform to the proposed tripartite system and whether the clustering pattern of elements of the linguistic profile suggests discrete clinical syndromes. METHODS: A total of 46 patients with PPA were prospectively recruited to the Cambridge Longitudinal Study of PPA. Sufficient data were collected to assess all consensus-proposed diagnostic domains. By comparing patients' performances against those of 30 age- and education-matched healthy volunteers, z scores were calculated, and values of 1.5 SDs outside control participants' means were considered abnormal. Raw test scores were used to undertake a principal factor analysis to identify the clustering pattern of individual measures. RESULTS: Of the patients, 28.3%, 26.1%, and 4.3% fitted semantic, nonfluent/agrammatic, and logopenic categories respectively, and 41.3% did not fulfill the diagnostic recommendations for any of the 3 proposed variants. There was no significant between-group difference in age, education, or disease duration. Furthermore, the outcome of the factor analysis was in keeping with discrete semantic and nonfluent/agrammatic syndromes but did not support a logopenic variant. CONCLUSION: Taken together, the results of this prospective data-driven study suggest that although a substantial proportion of patients with PPA have neither the semantic nor the nonfluent variants, they do not necessarily conform to a discrete logopenic variant.