Clinical value of Alzheimer's disease biomarker testing.

INTRODUCTION: In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing-used in medical care-impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics. METHODS: The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021. Patients referred to memory clinics were approached to participate if their dementia specialist ordered AD CSF biomarker testing as part of their routine medical care, and the clinical scenario met the appropriate use criteria for lumbar puncture and AD CSF biomarker testing. For the medical utility pillar, detailed clinical management plans were collected via physician questionnaires pre- and post-biomarker disclosure. RESULTS: Patients with completed management questionnaires (n = 142) had a median age of 64 (interquartile range: 59-69) years, 48% were female, and 60% had CSF biomarker profiles on the AD continuum. Clinical management changed in 89.4% of cases. AD biomarker testing was associated with decreased need for other diagnostic procedures, including brain imaging (-52.0%) and detailed neuropsychological assessments (-63.2%), increased referrals and counseling (57.0%), and guided AD-related drug prescriptions (+88.4% and -50.0% in biomarker-positive and -negative cases, respectively). DISCUSSION: AD biomarker testing was associated with significant and positive changes in clinical management, including decreased health care resource use, therapy optimization, and increased patient and family member counseling. While certain changes in management were linked to the AD biomarker profile (e.g., referral to clinical trials), the majority of changes were independent of baseline clinical presentation and level of cognitive impairment, demonstrating a broad value for AD biomarker testing in individuals meeting the appropriate use criteria for testing.

Clinicopathologic correlations in a family with a TBK1 mutation presenting as primary progressive aphasia and primary lateral sclerosis.

Mutations in the TANK binding kinase 1 gene (TBK1) are associated with amyotrophic lateral sclerosis and/or frontotemporal dementia; however, the range of clinical phenotypes and neuropathological changes associated with these mutations have not yet been completely elucidated. We present the detailed clinical, neuroimaging, and neuropathological features of two brothers carrying the TBK1 p.Gly272_Thr331del mutation. Both presented with very similar and unusual clinical features including primary progressive aphasia and asymmetric-onset primary lateral sclerosis (PLS). Repeated electrophysiological studies failed to reveal any lower motor neuron involvement. Neuropathological evaluation of both cases revealed frontotemporal lobar degeneration with TDP-43 proteinopathy type B and selective involvement of upper motor neurons with TDP-43 inclusions. The stereotypical clinical presentation and neuropathological findings in these cases widen the phenotypic spectrum of TBK1 mutations and provide insights into the pathogenesis of PLS.