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.

CCCDTD5 recommendations on the deprescribing of cognitive enhancers in dementia.

INTRODUCTION: Cognitive enhancers (ie, cholinesterase inhibitors and memantine) can provide symptomatic benefit for some individuals with dementia; however, there are circumstances in which the risks of continuing treatment may potentially outweigh benefits. The decision to deprescribe cognitive enhancers must consider each patient's preferences, treatment indications, current clinical status and symptoms, prognosis, and dementia type. METHODS: The 5th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD5) established a subcommittee of experts to review current evidence on the deprescribing of cognitive enhancers. The questions answered by this group included: When should cognitive enhancers be deprescribed in persons with dementia and mild cognitive impairment? How should cognitive enhancers be deprescribed? And, what clinical factors should be considered when deprescribing cognitive enhancers? RESULTS: Patient and care-partner preferences should be incorporated into all decisions to deprescribe cognitive enhancers. Cognitive enhancers should be discontinued in individuals without ongoing evidence of benefit or when the indication for cognitive enhancer use was inappropriate (eg, mild cognitive impairment). Deprescribing should occur gradually and cognitive enhancers should be reinitiated if patients' cognition or function deteriorates. Cognitive enhancers should be continued in individuals whose neuropsychiatric symptoms improve in response to treatment. Clinicians should not deprescribe cognitive enhancers in individuals with significant neuropsychiatric symptoms until symptoms have stabilized. CONCLUSION: CCCDTD5 deprescribing recommendations provide evidence-informed recommendations related to cognitive enhancer deprescribing that will facilitate shared decision making among patients, care partners, and clinicians.

12 Tips for Creating High Impact Clinical Encounter Videos - with Technical Pointers.

This article was migrated. The article was marked as recommended. Videos are increasingly used in medical education. They are effective for teaching difficult-to-grasp concepts that rely heavily on visuospatial processing ability such as anatomy, surgical procedures, and physical exam maneuvers. Common pitfalls of existing videos include lackluster audiovisual quality, poor camera angles, absence of formal teaching as narration, or excessive length. This article serves to assist educators who wish to produce educational clinical encounter videos that maximize student learning. We detail 12 tips focused on improving the quality of clinical educational videos, mitigating cognitive load within a video, and understanding the technicalities of video production. These tips are based on review of existing literature on neurocognitive learning theories and the succeeding Cognitive Theory of Multimedia Learning (CTML), as well as our experience in producing educational videos.

Clinical Assessment of Prefrontal Lobe Functions.

PURPOSE OF REVIEW: Whereas it was previously thought that there was a single overarching frontal lobe syndrome, it is now clear that several distinct cognitive and behavioral processes are mediated by the frontal lobes. This article reviews these processes and the underlying neuroanatomy and provides an approach to the assessment of prefrontal lobe functions at the bedside. RECENT FINDINGS: Cognitive and behavioral frontal lobe functions are mediated by the prefrontal regions rather than the frontal lobes as a whole. At least five separate prefrontal functions have been defined: energization, task setting, monitoring, behavioral/emotional regulation, and metacognition. Energization is mediated by the superior medial prefrontal cortices bilaterally, task setting by the left lateral frontal cortex, monitoring by the right lateral prefrontal cortex, behavioral/emotional regulation by the orbitofrontal cortex, and metacognition by the frontal poles. Only task setting and monitoring are considered executive functions. SUMMARY: Distinct cognitive and behavioral processes are mediated by different parts of the frontal lobe. Lesions in these areas result in characteristic clinical deficits that are discussed in this article. Key messages are that prefrontal regions mediate the higher cortical functions (as opposed to the frontal lobes in general) and that prefrontal functions are not equivalent to executive functions.

Cerebrospinal Fluid Biomarkers as Predictors of Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review.

BACKGROUND: The widely accepted treatment for idiopathic normal-pressure hydrocephalus (iNPH) is a cerebrospinal fluid (CSF) diversion shunt procedure, to which approximately 80% of patients will respond. The purpose of this systematic review was to identify which CSF biomarkers have been investigated in predicting shunt responsiveness in iNPH patients, and to analyze the level of evidence for each. METHODS: To find all relevant articles, a comprehensive search of Medline, Embase, and PsycINFO was conducted. RESULTS: The literature search identified 344 unique citations, of which 13 studies satisfied the inclusion criteria and were analyzed in our review. These 13 studies reported on 37 unique biomarkers. CONCLUSIONS: The available studies suggest that there is evidence for the utility of CSF biomarkers in predicting shunt responsiveness in iNPH patients, though none have been shown to predict shunt response with both high sensitivity and specificity. We found that there is no available evidence for the use of Aß38, Aß40, Aß43, APL1ß25, APL1ß27, APL1ß28, sAPP, aAPPα, sAPPß, TNF-α, MCP-1, sCD40L, sulfatide, MBP, L-PGDS, cystatin C, transthyretin, TGF-ß2, or YKL-40 in predicting shunt response. There is minimal evidence for the use of TGF-ß1, TBR-II, homocysteine, and interleukins (particularly IL-1ß, IL-6, and IL-10). However, the available evidence suggests that these biomarkers warrant further investigation. Aß42, tau, p-tau, NFL, and LRG have the greatest amount of evidence for their predictive value in determining shunt responsiveness in iNPH patients. Future research should be guided by, but not limited to, these biomarkers.

Clomipramine in the treatment of compulsive behavior in frontotemporal dementia: a case series.

Compulsive behaviors in patients with behavioral variant frontotemporal dementia (bvFTD) occur frequently and are challenging to manage. We report three cases of probable bvFTD associated with compulsive behaviors that responded well to treatment with clomipramine at daily dosages varying from 20 to 175 mg. The titration approach involved an initial 10-mg dose that was subsequently increased in 10 mg increments on a weekly basis until symptom relief without intolerable side effects. Our case series supports the consideration for a therapeutic trial with clomipramine in bvFTD when compulsive behavior occurs in these patients. It also highlights the need for further research on pharmacological treatments in bvFTD.

Ventromedial frontal lobe damage disrupts the accuracy, but not the speed, of value-based preference judgments.

The ventromedial frontal lobe (VMF) plays a role in decision making, but its precise function remains unclear. Several lines of evidence suggest that VMF is involved in representing the economic value of options. A prior study from our lab has shown that patients with lesions to the VMF are less consistent than controls in making simple preference judgments between stimuli presented in pairs. Here, we followed up that observation in a larger sample, using more sensitive tasks, and examining the category-specificity of this effect. Patients with damage to VMF (N=15) were compared to patients with frontal damage sparing that region (N=8) and to demographically matched healthy control participants (N=23). Five separate preference tasks were administered, requiring subjects to indicate their preference for 12 stimuli presented two at a time, in all possible combinations. Categories included fruits, vegetables, colors, landscapes, and puppies. Choices were analyzed for internal consistency, and decision times were measured. Three control tasks with the same format, but requiring perceptual judgments, were also administered. VMF patients were significantly more erratic than both non-VMF and healthy control participants in their preference judgments across all stimulus categories. However, decision times, and the relationship between decision time and relative value, were similar to that seen in control participants. The groups did not differ in perceptual judgment performance. These findings add further weight to the claim that VMF plays a critical role in simple value-based decision-making under conditions of certainty. This region appears to be necessary for consistent choices across a variety of stimulus categories, supporting the view that human VMF represents the (relative) value of decision options rather generally. That such damage impairs decision 'accuracy' without affecting reaction time has implications for theories of the role of VMF in decision-making, arguing that this region may be critical for linking a particular value to a particular option.