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.

Applying the Alzheimer Disease ATN Diagnostic Framework in Atypical Dementia.

Cerebrospinal fluid (CSF) biomarkers amyloid-ß and tau have been validated for the antemortem diagnosis of Alzheimer disease (AD) and are included in the AT(N) research framework for AD. Recently, an AT(N) CSF profile has been described for dementia with Lewy bodies (DLB), a disorder which is difficult to distinguish clinically from AD, particularly early in the disease course. Herein we describe a 71-year old male who presented with an atypical dementia syndrome including years of stability after an initial abrupt decline, marked visuospatial dysfunction, and relative sparing of memory. CSF biomarkers combined with the pattern of cognitive symptoms made AD unlikely and were consistent with DLB. This classification was confirmed clinically, with the emergence of classic DLB symptoms, and at postmortem pathologic examination. This case highlights the role for AD CSF biomarkers in facilitating earlier diagnosis of non-Alzheimer neurodegenerative dementias.

Rapidly expanding venous intracerebral haemorrhage with spot sign.

A 79-year-old woman was brought to the hospital with an acute-onset left haemiparesis. On initial examination, she had a pure sensorimotor syndrome with left-sided weakness and sensory disturbance. Her mental status was normal. She had normal visual fields to confrontation and no neglect. Her initial CT and CT angiogram revealed cerebral venous thrombosis with associated haemorrhage. A 'spot sign' was visible on CT angiogram. Immediately following the CT scan, the patient had a rapidly progressive decline in level of consciousness, requiring endotracheal intubation. A follow-up CT scan 70 min later showed the haemorrhage had expanded dramatically, with mass effect, midline shift and herniation. After a discussion with the family, the patient was extubated and died the following day. This is the first case of a cerebral venous thrombosis with associated spot sign-positive haemorrhage and published clinical details that the authors are aware of.

What is the relationship between type 2 diabetes mellitus status and the neuroradiological correlates of cerebral small vessel disease in adults? Protocol for a systematic review.

BACKGROUND: Cerebral small vessel disease (CSVD) is a common cause of stroke, dementia, and functional decline. In recent years, neuroradiologic correlates of CSVD have been identified. These imaging findings, best characterized on magnetic resonance imaging (MRI), include some combination of white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy. Though some cohorts have reported that participants with type 2 diabetes mellitus (T2DM), an important risk factor for CSVD, may have a distinct neuroradiologic phenotype, this relationship is not well-characterized. Adults with diabetes mellitus have a two- to threefold higher incidence of ischemic stroke compared to controls and are an increasingly important population given global trends of increasing diabetes prevalence. This study aims to determine if adults with CSVD and T2DM have a distinct neuroradiologic phenotype. METHODS: A systematic search of the literature will be conducted to find articles that report the MRI features of CSVD in a cohort of participants including those with and without type 2 diabetes mellitus (T2DM). A number of databases will be searched including MEDLINE, Embase, CINAHL, and Web of Science. Proceedings and abstracts from key conferences will also be reviewed and relevant journals hand searched for additional papers. The references from selected papers will be scanned. Screening of potential articles, data extraction, and quality appraisal will be performed in duplicate by independent reviewers. Odds ratios and 95% confidence intervals for the presence versus absence of each neuroradiologic correlate of interest from each included study will be calculated. If sufficient homogeneity exists among studies, a meta-analysis will be performed for each neuroradiologic correlate of CSVD. If heterogeneity of studies precludes data pooling, results will be presented in narrative form. DISCUSSION: Determining whether a distinct neuroradiologic phenotype of CSVD exists in adults with T2DM will provide insight into the underlying mechanisms of CSVD and guide future research on therapeutic targets. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016046669.