Browsing by Author "Small, Gary W."

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    PET of Brain Prion Protein Amyloid in Gerstmann–Sträussler–Scheinker Disease
    (Wiley, 2010-03) Kepe, Vladimir; Ghetti, Bernardino; Farlow, Martin R.; Bresjanac, Mara; Miller, Karen; Huang, Sung-Cheng; Wong, Koon-Pong; Murrell, Jill R.; Piccardo, Pedro; Epperson, Francine; Repovš, Grega; Smid, Lojze M.; Petrič, Andrej; Siddarth, Prabha; Liu, Jie; Satyamurthy, Nagichettiar; Small, Gary W.; Barrio, Jorge R.; Pathology and Laboratory Medicine, School of Medicine
    In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann-Sträussler-Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d-glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism ([F-18]FDG) reduction was observed in neocortex, basal ganglia and/or thalamus, which supports the close relationship between [F-18]FDDNP binding and neuronal dysfunction. Two asymptomatic gene carriers displayed no cortical [F-18]FDDNP binding, yet progressive [F-18]FDDNP retention in caudate nucleus and thalamus was seen at 1- and 2-year follow-up in the older asymptomatic subject. In vitro FDDNP labeling experiments on brain tissue specimens from deceased GSS subjects not participating in the in vivo studies indicated that in vivo accumulation of [F-18]FDDNP in subcortical structures, neocortices and cerebellum closely related to the distribution of prion protein pathology. These results demonstrate the feasibility of detecting prion protein accumulation in living patients with [F-18]FDDNP PET, and suggest an opportunity for its application to follow disease progression and monitor therapeutic interventions.
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    Understanding barriers to and facilitators of clinician-patient conversations about brain health and cognitive concerns in primary care: a systematic review and practical considerations for the clinician
    (Springer Nature, 2023-11-06) Borson, Soo; Small, Gary W.; O’Brien, Quentin; Morrello, Andrea; Boustani, Malaz; Medicine, School of Medicine
    Background: Primary care clinicians (PCCs) are typically the first practitioners to detect cognitive impairment in their patients, including those with Alzheimer's disease or related dementias (ADRD). However, conversations around cognitive changes can be challenging for patients, family members, and clinicians to initiate, with all groups reporting barriers to open dialogue. With the expanding array of evidence-based interventions for ADRD, from multidomain care management to novel biotherapeutics for early-stage AD, incorporating conversations about brain health into routine healthcare should become a standard of care. We conducted a systematic review to identify barriers to and facilitators of brain health conversations in primary care settings. Methods: We systematically searched PubMed, Scopus, Web of Science, and the Cochrane Library for qualitative or quantitative studies conducted in the US between January 2000 and October 2022 that evaluated perceptions of cognition and provider-patient brain health conversations prior to formal screening for, or diagnosis of, mild cognitive impairment or ADRD. We assessed the quality of the included studies using the Mixed Methods Appraisal Tool. Results: In total, 5547 unique abstracts were screened and 22 articles describing 19 studies were included. The studies explored perceptions of cognition among laypersons or clinicians, or provider-patient interactions in the context of a patient's cognitive concerns. We identified 4 main themes: (1) PCCs are hesitant to discuss brain health and cognitive concerns; (2) patients are hesitant to raise cognitive concerns; (3) evidence to guide clinicians in developing treatment plans that address cognitive decline is often poorly communicated; and (4) social and cultural context influence perceptions of brain health and cognition, and therefore affect clinical engagement. Conclusions: Early conversations about brain health between PCCs and their patients are rare, and effective tools, processes, and strategies are needed to make these vital conversations routine.