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BACKGROUND: Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks. A key question for the field is the extent to which participants can adhere to research protocols and the completeness of data collected. We aimed to describe drop out and data completeness in a naturalistic multimodal longitudinal RMT study, in people with a history of recurrent MDD. We further aimed to determine whether those experiencing a depressive relapse at baseline contributed less complete data. METHODS: Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) is a multi-centre, prospective observational cohort study conducted as part of the Remote Assessment of Disease and Relapse - Central Nervous System (RADAR-CNS) program. People with a history of MDD were provided with a wrist-worn wearable device, and smartphone apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks, and cognitive assessments. Participants were followed-up for a minimum of 11 months and maximum of 24 months. RESULTS: Individuals with a history of MDD (n = 623) were enrolled in the study,. We report 80% completion rates for primary outcome assessments across all follow-up timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. In total, 110 participants had > 50% data available across all data types. CONCLUSIONS: RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible. We found comparable levels of data availability in active and passive forms of data collection, demonstrating that both are feasible in this patient group.

OBJECTIVE: The study of cortical gyrification in Alzheimer's disease (AD) could help to further understanding of the changes undergone in the brain during neurodegeneration. Here, we aimed to study brain gyrification differences between healthy controls (HC), mild cognitive impairment (MCI) patients, and AD patients, and explore how cerebral gyrification patterns were associated with memory and other cognitive functions. METHODS: We applied surface-based morphometry techniques in 2 large, independent cross-sectional samples, obtained from the Alzheimer's Disease Neuroimaging Initiative project. Both samples, encompassing a total of 1,270 participants, were analyzed independently. RESULTS: Unexpectedly, we found that AD patients presented a more gyrificated entorhinal cortex than HC. Conversely, the insular cortex of AD patients was hypogyrificated. A decrease in the gyrification of the insular cortex was also found in older HC participants as compared with younger HC, which argues against the specificity of this finding in AD. However, an increased degree of folding of the insular cortex was specifically associated with better memory function and semantic fluency, only in AD patients. Overall, MCI patients presented an intermediate gyrification pattern. All these findings were consistently observed in the two samples. INTERPRETATION: The marked atrophy of the medial temporal lobe observed in AD patients may explain the increased folding of the entorhinal cortex. We additionally speculate regarding alternative mechanisms that may also alter its folding. The association between increased gyrification of the insular cortex and memory function, specifically observed in AD, could be suggestive of compensatory mechanisms to overcome the loss of memory function. ANN NEUROL 2020 ANN NEUROL 2020;88:67-80.

Fluctuating asymmetry represents the degree to which the right and left side of the body are asymmetrical, and is a sign of developmental instability. Higher levels of fluctuating asymmetry have been observed in individuals within the schizophrenia spectrum. We aimed to explore the associations of fluctuating asymmetry with psychotic and affective symptoms in schizophrenia patients, as well as with propensity to these symptoms in non-clinical individuals. A measure of morphological fluctuating asymmetry was calculated for 39 patients with schizophrenia and 60 healthy individuals, and a range of clinical and subclinical psychiatric symptoms was assessed. Regression analyses of the fluctuating asymmetry measure were conducted within each group. In the patient cohort, fluctuating asymmetry was significantly associated with the hallucination and thought disorganisation scores. T-test comparisons revealed that the patients presenting either hallucinations or thought disorganisation were significantly more asymmetrical than were the healthy individuals, while the patients without these key symptoms were equivalent to the healthy individuals. A positive association with the anxiety score emerged in a subsample of 36 healthy participants who were rated on affective symptoms. These findings suggest that fluctuating asymmetry may be an indicator of clinical hallucinations and thought disorganisation rather than an indicator of schizophrenia disease.

The principal therapeutic procedures and when they are clinically indicated in the management of essential mixed cryoglobulinemia (EMC) have been the subject of much debate. This paper reviews current knowledge and our experience in the treatment of this complex disease. It is generally agreed that patients with purpura, the primary symptom of EMC, should avoid long periods of sitting or standing in the same position. Non-steroidal antiinflammatory drugs can be used for the management of arthralgias and/ or arthritis. Low dose steroids (0.5-0.3 mg/kg/die) are usually sufficient to control the purpura, arthralgias, arthritis and weakness, while larger doses (0.5-1.5 mg/kg/die) are needed to treat the renal involvement, peripheral neuropathy and serositis. Since the discovery of the association between EMC and viral infections, the appropriateness of cytotoxic drugs has been re-evaluated and they are no longer used. With the low antigen content diet, a regimen designed to restore a saturated mononuclear phagocytic system, good results have been obtained in the treatment of purpura, arthralgias, weakness and peripheral neuropathy. Furthermore, this dietary regimen may play a steroid sparing role. Plasma exchange is widely used in the management of severe renal involvement, hyperviscosity syndrome, sensory motor neuropathy and liver involvement in EMC.