A review of the enhanced CJD surveillance feasibility study in the elderly in Scotland, UK.

BACKGROUND: Variant Creutzfeldt - Jakob disease (vCJD) arose from dietary contamination with bovine-spongiform-encephalopathy (BSE). Because of concerns that vCJD-cases might be missed in the elderly, a feasibility study of enhanced CJD surveillance on the elderly was begun in 2016. Recruitment was lower than predicted. We describe a review of the challenges encountered in that study: identification, referral, and recruitment, and the effects of actions based on the results of that review. METHODS: Review was conducted in 2017. Study data for all eligible cases identified and referred from one participating service (Anne Rowling clinic (ARC)) was curated and anonymised in a bespoke database. A questionnaire was sent out to all the clinicians in medicine of the elderly, psychiatry of old age and neurology (including ARC) specialties in NHS Lothian, exploring possible reasons for low recruitment. RESULTS: Sixty-eight cases were referred from the ARC (March 2016-September 2017): 25% were recruited. Most cases had been referred because of diagnostic uncertainty. No difference was seen between those recruited and the non-recruited, apart from age and referrer. Twelve of 60 participating clinicians completed the questionnaire: only 4 had identified eligible cases. High workload, time constraints, forgetting to refer, unfamiliarity with the eligibility criteria, and the rarity of eligible cases, were some of the reasons given. Suggestions as to how to improve referral of eligible cases included: regular email reminders, feedback to referrers, improving awareness of the study, visible presence of the study team, and integration of the study with other research oriented services. These results were used to increase recruitment but without success. CONCLUSION: Recruitment was lower than predicted. Actions taken following a review at 21 months did not lead to significant improvement; recruitment remained low, with many families/patients declining to take part (75%). In assessing the failure to improve recruitment, two factors need to be considered. Firstly, the initial referral rate was expected to be higher because of existing patients already known to the clinical services, with later referrals being only newly presenting patients. Secondly, the unplanned absence of a dedicated study nurse. Searching digital records/anonymised derivatives to identify eligible patients could be explored.

Incidental Findings Identified on Head MRI for Investigation of Cognitive Impairment: A Retrospective Review.

INTRODUCTION: Incidental findings are common in presumed healthy volunteers but are infrequently studied in patients in a clinical context. OBJECTIVE: To determine the prevalence, nature, and management implications of incidental findings on head MRI in patients presenting with cognitive symptoms, and to quantify and describe unexpected MRI abnormalities that are of uncertain relevance to the patient's cognitive symptoms. METHODS: A single-centre retrospective review of patients attending a regional early-onset cognitive disorders clinic between March 2012 and October 2018. Medical records of consecutive patients who underwent head MRI were reviewed. Unexpected MRI findings were classified according to their severity and likelihood of being incidental. Markers of small vessel disease and cerebral atrophy were excluded. RESULTS: Records of 694 patients were reviewed (median age 60 years, 49.9% female), of whom 514 (74.1%) underwent head MRI. 54% of the patients received a diagnosis of a neurodegenerative disorder. Overall 111 incidental findings were identified in 100 patients of whom 18 patients (3.5%, 95% CI 2.2-5.6%) had 18 incidental findings classified as requiring additional medical evaluation. 82 patients (16%, 95% CI 13.0-19.5%) had 93 incidental findings without clearly defined diagnostic consequences. 17 patients (3.3%) underwent further investigations, 14 patients (2.7%) were referred to another specialist clinic and 3 patients (0.6%) were treated surgically. Two patients had MRI findings of uncertain relevance to their cognitive symptoms, necessitating prolonged clinic follow-up. CONCLUSION: Incidental findings are common in patients with cognitive impairment from this large clinic-based series; however, few required additional medical evaluation. These data could help inform discussions between clinicians and people with cognitive symptoms regarding the likelihood and potential implications of incidental imaging findings.

After sudden unexpected death in epilepsy: Lessons learned and the road forward.

The devastating effects of sudden unexpected death in epilepsy (SUDEP) can be difficult to navigate, even for experienced clinicians. Mounting evidence supports full disclosure of the risks of epilepsy to those affected and their caregivers, and recommendations from regulatory and professional groups encourage the same. Following a death, families are faced with tragedy, guilt, and sometimes anger. Clinicians are often called upon to provide information and support. The development of a comprehensive approach to SUDEP education requires careful consideration of the people living with epilepsy, facts about SUDEP and known risk factors, as well as experiences of families and care providers. In this article, we share the experiences of those working in SUDEP education and epilepsy care, including the voluntary sector. We explore the experience of bereaved families and clinicians, derive lessons from published research, highlight areas where more research is needed, and report on preliminary data from a nationwide study from France.

The diagnostic utility of 99mTc-HMPAO SPECT imaging: a retrospective case series from a tertiary referral early-onset cognitive disorders clinic.

BACKGROUND/AIMS: Patients with early-onset dementia (EOD) often present atypically, making an accurate diagnosis difficult. Single-photon emission-computed tomography (SPECT) provides an indirect measure of cerebral metabolic activity and can help to differentiate between dementia subtypes. This study aims to investigate the clinical utility of SPECT imaging in the diagnosis of early-onset Alzheimer's disease. METHODS: All patients attending a tertiary referral clinic specialising in EOD between April 2012 and October 2013 were included in the study. Statistical analysis of SPECT patterns with clinical diagnoses, Addenbrooke's Cognitive Examination version 3 scores, and magnetic resonance imaging (MRI) atrophy was undertaken. RESULTS: The results demonstrated a highly significant association between SPECT hypoperfusion patterns and clinical diagnoses. SPECT changes were demonstrated more frequently than MRI atrophy. CONCLUSIONS: The results suggest that SPECT imaging may be a useful adjunct to clinical evaluation and a more sensitive biomarker than standard structural imaging.

A systematic review and meta-analysis of (18)F-labeled amyloid imaging in Alzheimer's disease.

BACKGROUND: Amyloid imaging using fluorine 18-labeled tracers florbetapir, florbetaben, and flutemetamol has recently been reported in Alzheimer's disease (AD). METHODS: We systematically searched MEDLINE and EMBASE for relevant studies published from January 1980 to March 2014. Studies comparing imaging findings in AD and normal controls (NCs) were pooled in a meta-analysis, calculating pooled weighted sensitivity, specificity, and diagnostic odds ratio (OR) using the DerSimonian-Laird random-effects model. RESULTS: Nineteen studies, investigating 682 patients with AD, met inclusion criteria. Meta-analysis demonstrated a sensitivity of 89.6%, a specificity of 87.2%, and an OR of 91.7 for florbetapir in differentiating AD patients from NCs, and a sensitivity of 89.3%, a specificity of 87.6%, and a diagnostic OR of 69.9 for florbetaben. There were insufficient data to complete analyses for flutemetamol. CONCLUSIONS: Results suggest favorable sensitivity and specificity of amyloid imaging with fluorine 18-labeled tracers in AD. Prospective studies are required to determine optimal imaging analysis methods and resolve outstanding clinical uncertainties.

A systematic review and meta-analysis of retinal nerve fiber layer change in dementia, using optical coherence tomography.

INTRODUCTION: Retinal nerve fiber layer (RNFL) thinning, assessed by optical coherence tomography (OCT), has recently been reported in various dementias. METHODS: We conducted a systematic review and meta-analysis to investigate the diagnostic utility of RNFL thickness measurement using OCT in dementia (including Alzheimer's disease [AD] and mild cognitive impairment [MCI]) compared with healthy controls (HC). RESULTS: Seventeen studies comparing AD with HC (702 AD eyes and 790 HC eyes) were included, demonstrating a significant reduction in mean RNFL thickness in AD (weighted mean difference [WMD] 12.44, 95% confidence interval or CI [-16.64, -8.25], P <.0001). Five studies comparing MCI and HC (214 MCI eyes and 421 HC eyes) were included demonstrating a significant reduction in mean RNFL thickness in MCI (WMD -8.23, 95% CI [-14.00, -2.45], P =.005). No relevant studies were identified for other dementias. DISCUSSION: OCT measurement of RNFL thickness appears diagnostically useful in discriminating between AD, or MCI, and HC.