Adapted problem adaptation therapy for depression in mild to moderate Alzheimer's disease dementia: A randomized controlled trial.

INTRODUCTION: Trials of effectiveness of treatment options for depression in dementia are an important priority. METHODS: Randomized controlled trial to assess adapted Problem Adaptation Therapy (PATH) for depression in mild/moderate dementia caused by Alzheimer's disease. RESULTS: Three hundred thirty-six participants with mild or moderate dementia, >7 on Cornell Scale for Depression in Dementia (CSDD), randomized to adapted PATH or treatment as usual. Mean age 77.0 years, 39.0% males, mean Mini-Mental State Examination 21.6, mean CSDD 12.9. For primary outcome (CSDD at 6 months), no statistically significant benefit with adapted PATH on the CSDD (6 months: -0.58; 95% CI -1.71 to 0.54). The CSDD at 3 months showed a small benefit with adapted PATH (-1.38; 95% CI -2.54 to -0.21) as did the EQ-5D (-4.97; 95% CI -9.46 to -0.48). DISCUSSION: An eight-session course of adapted PATH plus two booster sessions administered within NHS dementia services was not effective treatment for depression in people with mild and moderate dementia. Future studies should examine the effect of more intensive and longer-term therapy.

Clinical and cost-effectiveness of DREAMS START (Dementia RElAted Manual for Sleep; STrAtegies for RelaTives) for people living with dementia and their carers: a study protocol for a parallel multicentre randomised controlled trial.

INTRODUCTION: Many people living with dementia experience sleep disturbance and there are no known effective treatments. Non-pharmacological treatment options should be the first-line sleep management. For family carers, relatives' sleep disturbance leads to interruption of their sleep, low mood and breakdown of care. Our team developed and delivered DREAMS START (Dementia RElAted Manual for Sleep; STrAtegies for RelaTives), a multimodal non-pharmacological intervention, showing it to be feasible and acceptable. The aim of this randomised controlled trial is to establish whether DREAMS START is clinically cost-effective in reducing sleep disturbances in people living with dementia living at home compared with usual care. METHODS AND ANALYSIS: We will recruit 370 participant dyads (people living with dementia and family carers) from memory services, community mental health teams and the Join Dementia Research Website in England. Those meeting inclusion criteria will be randomised (1:1) either to DREAMS START or to usual treatment. DREAMS START is a six-session (1 hour/session), manualised intervention delivered every 1-2 weeks by supervised, non-clinically trained graduates. Outcomes will be collected at baseline, 4 months and 8 months with the primary outcome being the Sleep Disorders Inventory score at 8 months. Secondary outcomes for the person with dementia (all proxy) include quality of life, daytime sleepiness, neuropsychiatric symptoms and cost-effectiveness. Secondary outcomes for the family carer include quality of life, sleep disturbance, mood, burden and service use and caring/work activity. Analyses will be intention-to-treat and we will conduct a process evaluation. ETHICS AND DISSEMINATION: London-Camden & Kings Cross Ethics Committee (20/LO/0894) approved the study. We will disseminate our findings in high-impact peer-reviewed journals and at national and international conferences. This research has the potential to improve sleep and quality of life for people living with dementia and their carers, in a feasible and scalable intervention. TRIAL REGISTRATION NUMBER: ISRCTN13072268.

Quantitative [123]I-Ioflupane DaTSCAN single-photon computed tomography-computed tomography in Parkinsonism.

AIM: [123]I-Ioflupane (DaTSCAN) binds to the presynaptic dopamine transporter (DAT) and with a lower affinity to the serotonin transporter (SERT). We aimed to develop a novel method to quantify absolute uptake in the striatal (predominantly DAT binding) and extra-striatal regions (mainly SERT binding) using single-photon computed tomography-computed tomography (SPECT-CT) DaTSCAN and to improve DaTSCAN image quality. METHOD: Twenty-six patients with Parkinsonism underwent DaTSCAN SPECT-CT prospectively. The scans were visually analyzed independently by two experienced reporters. Specific binding ratios (SBRs) from Chang attenuation corrected SPECT were obtained using GE DaTQuant. Normalized concentrations and specific uptakes (NSU) from measured attenuation and modelled scatter-corrected SPECT-CT were obtained using HERMES Hybrid Recon and Affinity and modified EARL volumes of interest. RESULTS: Striatal NSU and SBR positively correlate ( R  = 0.65-0.88, P  = 0.00). SBR, normalized concentrations, and NSU box plots differentiated between scans without evidence of dopaminergic deficit and abnormal scans. Interestingly, body weight inversely correlated with normalized concentrations values in extra-striatal regions [frontal ( R  = 0.81, P  = 0.00); thalamus ( R  = 0.58, P  = 0.00); occipital ( R  = 0.69, P  = 0.00)] and both caudate nuclei [ R  = 0.42, P  = 0.03 (Right), R  = 0.52, P  = 0.01 (Left)]. Both reporters noted improved visual quality of SPECT-CT versus SPECT images for all scans. CONCLUSION: DaTSCAN SPECT-CT resulted in more accurate quantification, improved image quality, and enabled absolute quantification of extra-striatal regions. More extensive studies are required to establish the full value of absolute quantification for diagnosis and monitoring the progression of neurodegenerative disease, to assess an interplay between DAT and SERT, and to verify whether serotonin and DATs are potentially dysfunctional in obesity.

Patient experience and satisfaction with remote memory assessment: Responding to clinical need in times of COVID-19 restrictions.

BACKGROUND: The suspension of memory services during the COVID-19 pandemic delayed dementia diagnosis and access to early intervention. Some services responded to the challenge by developing a remote memory assessment pathway to comply with reduced social contact measures to protect vulnerable patients. The aim of the study was to establish whether remote model is considered a satisfactory experience within the context of the COVID-19 pandemic and to understand the factors associated with patient and carer satisfaction of remote pathway. METHOD: 73 participants recruited from patients referred to memory clinic in West Sussex, who were assessed over a video or telephone. Participants completed an 11-item questionnaire capturing satisfaction across a range of elements, contextual items (the impact of the pandemic, loneliness, previous experience of using teleconference technology and diagnosis), as well as 3 dimensions from Patient Experience Questionnaire. Descriptive statistics are reported at a whole sample level, separated by patient and carer status. A hypothesis driven set of bivariate analyses (Spearman's rank) was used to understand the association between overall satisfaction and key independent factors across the whole sample. RESULTS: 73 participants were typically older adults (M=68.5, SD=13.3) and female (n=40, 54.8%). The patient was more likely to be older, feel lonely within the past week and to have used video call software when compared to the carer (p> 0.05). Participants were generally satisfied with the remote pathway with 95.8% (n=69) agreeing or strongly agreeing with the statement "Overall, I was satisfied with the assessment". Patients and carers did not significantly differ on any satisfaction response, apart from the ease of use of technology, in which carers were more likely to find the technology easy to use (U= 432.5; p=0.01). Worry about contracting COVID and communication experience was positively associated with overall satisfaction, whilst perceived communication barriers were significantly negatively associated with overall satisfaction. CONCLUSIONS: Remote memory assessment was a positive and satisfactory experience for most patient and carers. The remote pathway should be considered as an option available during and beyond the pandemic to improve access and patient choice of assessment modality.

Review of brief cognitive tests for patients with suspected dementia.

BACKGROUND: As the population ages, it is increasingly important to use effective short cognitive tests for suspected dementia. We aimed to review systematically brief cognitive tests for suspected dementia and report on their validation in different settings, to help clinicians choose rapid and appropriate tests. METHODS: Electronic search for face-to-face sensitive and specific cognitive tests for people with suspected dementia, taking ≤ 20 minutes, providing quantitative psychometric data. RESULTS: 22 tests fitted criteria. Mini-Mental State Examination (MMSE) and Hopkins Verbal Learning Test (HVLT) had good psychometric properties in primary care. In the secondary care settings, MMSE has considerable data but lacks sensitivity. 6-Item Cognitive Impairment Test (6CIT), Brief Alzheimer's Screen, HVLT, and 7 Minute Screen have good properties for detecting dementia but need further validation. Addenbrooke's Cognitive Examination (ACE) and Montreal Cognitive Assessment are effective to detect dementia with Parkinson's disease and Addenbrooke's Cognitive Examination-Revised (ACE-R) is useful for all dementias when shorter tests are inconclusive. Rowland Universal Dementia Assessment scale (RUDAS) is useful when literacy is low. Tests such as Test for Early Detection of Dementia, Test Your Memory, Cognitive Assessment Screening Test (CAST) and the recently developed ACE-III show promise but need validation in different settings, populations, and dementia subtypes. Validation of tests such as 6CIT, Abbreviated Mental Test is also needed for dementia screening in acute hospital settings. CONCLUSIONS: Practitioners should use tests as appropriate to the setting and individual patient. More validation of available tests is needed rather than development of new ones.

White matter microstructural abnormalities in the frontal lobe of adults with antisocial personality disorder.

UNLABELLED: Antisocial personality disorder (ASPD) and psychopathy involve significant interpersonal and behavioural impairments. However, little is known about their underlying neurobiology and in particular, abnormalities in white matter (WM) microstructure. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of adult psychopaths employing tractography revealed abnormalities in the right uncinate fasciculus (UF) (Craig et al., 2009), indicating fronto-limbic disconnectivity. However, it is not clear whether WM abnormalities are restricted to this tract or are or more widespread, including other tracts which are involved in connectivity with the frontal lobe. We performed whole brain voxel-based analyses on WM fractional anisotropy (FA) and mean diffusivity (MD) maps acquired with DT-MRI to compare 15 adults with ASPD and healthy age, handedness and IQ-matched controls. Also, within ASPD subjects we related differences in FA and MD to measures of psychopathy. Significant WM FA reduction and MD increases were found respectively in ASPD subjects relative to controls. FA was bilaterally reduced in the genu of corpus callosum while in the right frontal lobe FA reduction was found in the UF, inferior fronto-occipital fasciculus (IFOF), anterior corona radiata and anterior limb and genu of the internal capsule. These differences negatively correlated with measures of psychopathy. Also in the right frontal lobe, increased MD was found in the IFOF and UF, and the corpus callosum and anterior corona radiata. There was a significant positive correlation between MD and psychopathy scores. CONCLUSIONS: The present study confirms a previous report of reduced FA in the UF. Additionally, we report for the first time, FA deficits in tracts involved in interhemispheric as well as frontal lobe connectivity in conjunction with MD increases in the frontal lobe. Hence, we provide evidence of significant WM microstructural abnormalities in frontal brain regions in ASPD and psychopathy.