Scottish Intercollegiate Guidelines Network Guidance on Dementia: The Investigation of Suspected Dementia (SIGN 168) with Focus on Biomarkers-Executive Summary.

This is an executive summary of the recent guidance produced by the Scottish Intercollegiate Guidelines Network (SIGN) dementia guideline group with regards to the investigation of suspected dementia. This is a sub-section of the broader SIGN 168 guideline released in November 2023. The guideline group included clinicians with expertise in Old Age Psychiatry, Neurology, Radiology, and Nuclear Medicine supported by colleagues from the SIGN and Healthcare Improvement Scotland teams. There was representation from carers and support organizations with experience of dementia, to ensure the recommendations were appropriate from the perspective of the people being assessed for possible dementia and their carers. As the 2018 National Institute for Health and Clinical Excellence (NICE) dementia review included a review of the evidenced investigation of dementia, the SIGN guideline development group decided to focus on a review on the up-to-date evidence regarding the role of imaging and fluid biomarkers in the diagnosis of dementia. To give context to the consideration of more advanced diagnostic biomarker investigations, the guideline and this summary include the NICE guidance on the use of standard investigations as well as more specialist investigations. The evidence review supports consideration of the use of structural imaging, nuclear medicine imaging, and established Alzheimer's cerebrospinal fluid biomarkers (amyloid and tau) in the diagnosis of dementia. Although routine use of amyloid positron emission tomography imaging was not recommended, its potential use, under specialist direction, in patients with atypical or young-onset presentations of suspected Alzheimer's dementia was included as a clinical good practice point.

Ideal refocusing of an optically active spin qubit under strong hyperfine interactions.

Combining highly coherent spin control with efficient light-matter coupling offers great opportunities for quantum communication and computing. Optically active semiconductor quantum dots have unparalleled photonic properties but also modest spin coherence limited by their resident nuclei. The nuclear inhomogeneity has thus far bound all dynamical decoupling measurements to a few microseconds. Here, we eliminate this inhomogeneity using lattice-matched GaAs-AlGaAs quantum dot devices and demonstrate dynamical decoupling of the electron spin qubit beyond 0.113(3) ms. Leveraging the 99.30(5)% visibility of our optical π-pulse gates, we use up to Nπ = 81 decoupling pulses and find a coherence time scaling of [Formula: see text]. This scaling manifests an ideal refocusing of strong interactions between the electron and the nuclear spin ensemble, free of extrinsic noise, which holds the promise of lifetime-limited spin coherence. Our findings demonstrate that the most punishing material science challenge for such quantum dot devices has a remedy and constitute the basis for highly coherent spin-photon interfaces.

Cognition and behaviour in frontotemporal dementia with and without amyotrophic lateral sclerosis.

OBJECTIVE: The precise relationship between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is incompletely understood. The association has been described as a continuum, yet data suggest that this may be an oversimplification. Direct comparisons between patients who have behavioural variant FTD (bvFTD) with and without ALS are rare. This prospective comparative study aimed to determine whether there are phenotypic differences in cognition and behaviour between patients with FTD-ALS and bvFTD alone. METHODS: Patients with bvFTD or FTD-ALS and healthy controls underwent neuropsychological testing, focusing on language, executive functions and social cognition. Behavioural change was measured through caregiver interview. Blood samples were screened for known FTD genes. RESULTS: 23 bvFTD, 20 FTD-ALS and 30 controls participated. On cognitive tests, highly significant differences were elicited between patients and controls, confirming the tests' sensitivities to FTD. bvFTD and FTD-ALS groups performed similarly, although with slightly greater difficulty in patients with ALS-FTD on category fluency and a sentence-ordering task that assesses grammar production. Patients with bvFTD demonstrated more widespread behavioural change, with more frequent disinhibition, impulsivity, loss of empathy and repetitive behaviours. Behaviour in FTD-ALS was dominated by apathy. The C9ORF72 repeat expansion was associated with poorer performance on language-related tasks. CONCLUSIONS: Differences were elicited in cognition and behaviour between bvFTD and FTD-ALS, and patients carrying the C9ORF72 repeat expansion. The findings, which raise the possibility of phenotypic variation between bvFTD and FTD-ALS, have clinical implications for early detection of FTD-ALS and theoretical implications for the nature of the relationship between FTD and ALS.

The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) in frontotemporal dementia.

OBJECTIVES: To examine the usefulness of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS) as a cognitive screening tool for the detection of behavioral variant frontotemporal dementia (bvFTD). A secondary aim was to determine whether people with FTD combined with ALS (ALS-FTD) exhibit a similar ECAS profile to that of people with bvFTD alone. Methods: Patients with ALS-FTD and bvFTD and healthy controls were recruited. Participants were administered the ECAS, which comprises tests of language, verbal fluency, executive functions, memory, and visual-spatial functions. They also carried out analogous, full-length cognitive tests that examine naming, spelling, sentence completion, and social cognition skills. Results: The study cohort comprised 20 ALS-FTD patients, 23 with bvFTD, and 30 controls. Highly significant group differences were elicited for all cognitive domains, reflecting poorer performance in patients compared to controls. No significant differences in overall test scores were found between ALS-FTD and bvFTD patients, although ALS-FTD patients showed a higher frequency of impairment on verbal fluency. Correlative analyses revealed inter-relationships in patients (but not controls) between scores in different domains, most marked in bvFTD. There were strong correlations between performance on ECAS subtests and analogous cognitive tasks. Conclusion: The ECAS is a sensitive and valuable tool for the assessment of FTD. Executive, language and behavioral breakdown may, however, compromise performance in other cognitive domains, reducing the specificity of the 'frontotemporal' cognitive profile. Subtle differences observed between ALS-FTD and bvFTD raise questions regarding the precise relationship between bvFTD with and without ALS.

Collective Quantum Memory Activated by a Driven Central Spin.

Coupling a qubit coherently to an ensemble is the basis for collective quantum memories. A single driven electron in a quantum dot can deterministically excite low-energy collective modes of a nuclear spin ensemble in the presence of lattice strain. We propose to gate a quantum state transfer between this central electron and these low-energy excitations-spin waves-in the presence of a strong magnetic field, where the nuclear coherence time is long. We develop a microscopic theory capable of calculating the exact time evolution of the strained electron-nuclear system. With this, we evaluate the operation of quantum state storage and show that fidelities up to 90% can be reached with a modest nuclear polarization of only 50%. These findings demonstrate that strain-enabled nuclear spin waves are a highly suitable candidate for quantum memory.

Co-Occurrence of Language and Behavioural Change in Frontotemporal Lobar Degeneration.

BACKGROUND/OBJECTIVES: We aimed to evaluate the co-occurrence of language and behavioural impairment in patients with frontotemporal lobar degeneration (FTLD) spectrum pathology. METHODS: Eighty-one dementia patients with pathological confirmation of FTLD were identified. Anonymized clinical records from patients' first assessment were rated for language and behavioural features from frontotemporal dementia consensus criteria, primary progressive aphasia (PPA) criteria and 1998 FTLD criteria. RESULTS: Over 90% of patients with FTLD pathology exhibited a combination of at least one behavioural and one language feature. Changes in language, in particular, were commonly accompanied by behavioural change. Notably, the majority of patients who displayed language features characteristic of semantic variant PPA exhibited 'early perseverative, stereotyped or compulsive/ritualistic behaviour'. Moreover, 'executive/generation deficits with relative sparing of memory and visuospatial functions' occurred in most patients with core features of non-fluent variant PPA. CONCLUSION: Behavioural and language symptoms frequently co-occur in patients with FTLD pathology. Current classifications, which separate behavioural and language syndromes, do not reflect this co-occurrence.

Morvan Syndrome: A Case Report With Patient Narrative and Video.

A 74-year-old gentleman was admitted to the regional neurosciences center with encephalopathy, myokymia, and dysautonomia. Chest imaging had previously identified an incidental mass in the anterior mediastinum, consistent with a primary thymic tumor. Antivoltage-gated potassium channel (anti-VGKC) antibodies were positive (titer 1273 pmol/L) and he was hypokalemic. Electromyogram and nerve conduction studies were in keeping with peripheral nerve hyperexcitability syndrome, and an electroencephalogram was consistent with encephalopathy. A diagnosis of Morvan syndrome was made, for which he was initially treated with high-dose steroids, followed by a 5-day course of intravenous immunoglobulin (IVIG) therapy. He also underwent thymectomy, followed by a postexcision flare of his symptoms requiring intensive care management. Further steroids, plasmapheresis, and IVIG achieved stabilization of his clinical condition, enabling transfer for inpatient neurorehabilitation. He was commenced on azathioprine and a prolonged oral steroid taper. A subsequent presumed incipient relapse responded well to further IVIG treatment. This case report documents a thymoma-associated presentation of anti-VGKC-positive Morvan syndrome supplemented by patient and carer narrative and video, both of which provide valuable further insights into this rare disorder. There are a limited number of publications surrounding this rare condition available in the English literature. This, combined with the heterogenous presentation, association with underlying malignancy, response to treatment, and prognosis, provides a diagnostic challenge. However, the association with anti-VGKC antibody-associated complexes and 2 recent case series have provided some scope for both accurate diagnosis and management.

Quadrature squeezed photons from a two-level system.

Resonance fluorescence arises from the interaction of an optical field with a two-level system, and has played a fundamental role in the development of quantum optics and its applications. Despite its conceptual simplicity, it entails a wide range of intriguing phenomena, such as the Mollow-triplet emission spectrum, photon antibunching and coherent photon emission. One fundamental aspect of resonance fluorescence--squeezing in the form of reduced quantum fluctuations in the single photon stream from an atom in free space--was predicted more than 30 years ago. However, the requirement to operate in the weak excitation regime, together with the combination of modest oscillator strength of atoms and low collection efficiencies, has continued to necessitate stringent experimental conditions for the observation of squeezing with atoms. Attempts to circumvent these issues had to sacrifice antibunching, owing to either stimulated forward scattering from atomic ensembles or multi-photon transitions inside optical cavities. Here, we use an artificial atom with a large optical dipole enabling 100-fold improvement of the photon detection rate over the natural atom counterpart and reach the necessary conditions for the observation of quadrature squeezing in single resonance-fluorescence photons. By implementing phase-dependent homodyne intensity-correlation detection, we demonstrate that the electric field quadrature variance of resonance fluorescence is three per cent below the fundamental limit set by vacuum fluctuations, while the photon statistics remain antibunched. The presence of squeezing and antibunching simultaneously is a fully non-classical outcome of the wave-particle duality of photons.

Do NIA-AA criteria distinguish Alzheimer's disease from frontotemporal dementia?

BACKGROUND: Clinical criteria are important for improving diagnostic accuracy and ensuring comparability of patient cohorts in research studies. OBJECTIVE: The aim was to assess the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for Alzheimer's disease (AD) dementia in AD and frontotemporal lobar degeneration (FTLD). METHODS: Two hundred twelve consecutive patients with pathologically confirmed AD or FTLD who were clinically assessed in a specialist cognitive unit were identified. Fifty-five patients were excluded predominantly because of insufficient clinical information. Anonymized clinical data were rated against the NIA-AA criteria by raters who were blinded to clinical and pathologic diagnosis. RESULTS: The NIA-AA AD dementia criteria had a sensitivity of 65.6% for probable and 79.5% for possible AD and a specificity of 95.2% and 94.0% for probable and possible, respectively. CONCLUSION: In patients with FTLD and predominantly early-onset AD, the NIA-AA AD dementia criteria have high specificity but lower sensitivity. The high specificity is due to the broad exclusion criteria.

Classification and pathology of primary progressive aphasia.

OBJECTIVE: We aimed to determine the extent to which patients with progressive language impairment conform to 2011 primary progressive aphasia (PPA) classification and to examine clinicopathologic correlations within PPA variants. METHODS: Sixty-two consecutive patients with pathologically confirmed dementia who presented clinically with aphasia were identified. Patients with insufficient clinical information were excluded. PPA classifications were applied to anonymized clinical data taken from patients' initial assessment by raters who were blinded to clinical and pathologic diagnosis. RESULTS: The final cohort comprised 52 patients, 30 of whom met basic PPA criteria. Twenty-five patients met one of the 3 PPA classifications (13 logopenic, 8 nonfluent/agrammatic, and 4 semantic). Five patients did not meet the criteria for any of the PPA variants. All patients who met semantic variant PPA and 75% of patients who met nonfluent/agrammatic variant PPA classifications had frontotemporal lobar degeneration spectrum pathology. Pathologies were heterogeneous in patients who met logopenic variant PPA criteria (46% Alzheimer disease [AD], 8% AD mixed with dementia with Lewy bodies, 23% frontotemporal lobar degeneration, and 23% other). CONCLUSION: The 2011 PPA recommendations classify a large proportion of patients who meet basic PPA criteria. However, some patients had aphasic syndromes that could not be classified, suggesting that the 2011 recommendations do not cover the full range of PPA variants. Classification of semantic variant PPA provides a good prediction of underlying pathology. Classification of logopenic variant does not successfully differentiate PPA due to AD from PPA due to other pathologies.

Sensitivity and specificity of FTDC criteria for behavioral variant frontotemporal dementia.

OBJECTIVE: We aimed to assess sensitivity and specificity of the updated criteria for behavioral variant frontotemporal dementia (bvFTD) based on a large autopsy-confirmed cohort of patients with dementia. METHODS: Two hundred thirty-nine consecutive pathologically confirmed dementia patients, clinically assessed in a specialist cognitive unit were identified. Patients with predominant aphasia, motor disorders, or insufficient clinical information were excluded. Frontotemporal Dementia Consensus criteria were applied to anonymized clinical data taken from patients' initial assessment by raters who were blinded to clinical and pathologic diagnosis. RESULTS: The final study cohort comprised 156 patients with predominantly early-onset dementia. The updated criteria for possible bvFTD had a sensitivity of 95% and specificity of 82%. Probable bvFTD criteria had a sensitivity of 85% and specificity of 95%. False positives were predominantly patients with presenile Alzheimer disease. CONCLUSION: Revised diagnostic criteria show encouragingly high sensitivity and specificity when applied to patients with early-onset dementia. They therefore provide a useful tool both for specialist researchers and general clinicians. There is a need for further prospective studies of sensitivity and specificity involving a broader spectrum of patients with dementia.

Phase-locked indistinguishable photons with synthesized waveforms from a solid-state source.

Resonance fluorescence in the Heitler regime provides access to single photons with coherence well beyond the Fourier transform limit of the transition, and holds the promise to circumvent environment-induced dephasing common to all solid-state systems. Here we demonstrate that the coherently generated single photons from a single self-assembled InAs quantum dot display mutual coherence with the excitation laser on a timescale exceeding 3 s. Exploiting this degree of mutual coherence, we synthesize near-arbitrary coherent photon waveforms by shaping the excitation laser field. In contrast to post-emission filtering, our technique avoids both photon loss and degradation of the single-photon nature for all synthesized waveforms. By engineering pulsed waveforms of single photons, we further demonstrate that separate photons generated coherently by the same laser field are fundamentally indistinguishable, lending themselves to the creation of distant entanglement through quantum interference.

Five cases of new onset refractory status epilepticus (NORSE) syndrome: outcomes with early immunotherapy.

UNLABELLED: Cryptogenic new onset refractory status epilepticus (NORSE) syndrome has been described in both adults and children, and is often associated with poor outcome. A variety of terms have been used in the literature to refer to this syndrome. The condition may be triggered by as yet unidentified infections or an immunological mechanism. We present a series of 5 patients with NORSE syndrome treated at 2 neuroscience centres in the North of England, in whom early use of immunotherapy appears to be associated with good neurological outcomes. METHODS: Case note review of the index case and four other patients was undertaken to obtain details of clinical presentation, imaging and CSF findings, infectious/inflammatory tests, management of seizures, immunotherapy and outcome. RESULTS: Case 1 was a 26 year old male with a prodrome of headache and vomiting. He developed refractory multifocal and generalised seizures, which required admission to intensive care unit and administration of general anaesthetic. Seizures recurred on withdrawal of barbiturate anaesthetic until day 29. MR imaging, CSF examination and serological tests for viral and autoimmune aetiologies were normal apart from positive anti-TPO antibodies: the patient had previously treated hyperthyroidism. He was initially treated with aciclovir and antibacterials. IV steroids were administered day 12 and IV immunoglobulin day 18. He made a good recovery being discharged home 2 months after admission. Seizures recurred on withdrawal of steroid therapy, and required longer term immunosuppressant treatment with azathioprine. Clinical features and investigations of the four other patients were similar. Two were given early immunotherapy with steroids and intravenous immunoglobulins and survived with few deficits. One patient who was not given immunotherapy died from complications associated with prolonged ICU stay. Outcome was not known for the fourth patient as she was repatriated to her home country in thiopentone coma. CONCLUSION: In our experience, early immunotherapy has been associated with good outcomes in NORSE. Multicentre collaboration is required to establish the diagnostic criteria and appropriate management of patients presenting with NORSE.

Effects of ID-alG™ on weight management and body fat mass in high-fat-fed rats.

Seaweed extract of Ascophyllum nodosum, ID-alG™, was evaluated for its chronic effects on weight management in high-fat-fed Sprague-Dawley rats. ID-alG™ was orally administered daily during 9 weeks at doses of 40 and 400 mg/kg/day with fat-enriched diet (FED) in comparison with two control groups consuming standard diet (negative control) or FED (positive control) and orally treated with vehicle. Body weight, percentage of body fat mass and lipid parameters were measured. After 9 weeks, the oral administration of ID-alG™ at both doses decreased significantly the mean body weight gains (MBWG) of rats submitted to the FED in comparison to the positive control (-6.8% and -11.8%). ID-alG™ at both doses improved significantly the MBWG of rats and decreased significantly the percentage of body fat mass of rats (-9.8% and -19.0%), in comparison to the positive control. In the same way, the triglyceride blood level was also significantly improved for the dose of 400 mg/kg/day (-30.6% vs. +49.9% for the positive control); and the dose of 40 mg/kg/day just lead to a trend. Moreover, in both controls and ID-alG™-treated groups, total cholesterol, LDL and HDL blood levels were not modified. The seaweed extract of Ascophyllum nodosum, ID-alG™, demonstrated beneficial effects on weight management of rats submitted to a high-fat diet.