Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial.

INTRODUCTION: Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, 'Multiple Sclerosis International Stem Cell Transplant, MIST', showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS. METHODS AND ANALYSIS: StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve 'no evidence of disease activity' during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs. ETHICS AND DISSEMINATION: The study was approved by the Yorkshire and Humber-Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN88667898.

Highly Superior Autobiographical Memory (HSAM): A Systematic Review.

Individuals possessing a Highly Superior Autobiographical Memory (HSAM) demonstrate an exceptional ability to recall their own past, excelling most when dates from their lifetime are used as retrieval cues. Fully understanding how neurocognitive mechanisms support exceptional memory could lead to benefits in areas of healthcare in which memory plays a central role and in legal fields reliant on witnesses' memories. Predominantly due to the rareness of the phenomenon, existing HSAM literature is highly heterogenous in its methodologies used. Therefore, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed the first systematic review on this topic, to collate the existing behavioural, neuroanatomical, and functional HSAM data. Results from the 20 experimental selected studies revealed that HSAM is categorised by rapidly retrieved, detailed and accurate autobiographical memories, and appears to avoid the normal aging process. Functional neuroimaging studies showed HSAM retrieval seems characterised by an intense overactivation of the usual autobiographical memory network, including posterior visual areas (e.g., the precuneus). Structural neuroanatomical differences do not appear to characterise HSAM, but altered hippocampal resting-state connectivity was commonly observed. We discuss theories of HSAM in relation to autobiographical encoding, consolidation, and retrieval, and suggest future directions for this research.

The relationship between transliminality, hypnotic and imaginative suggestibility, and other personality traits.

To our knowledge, no study has directly examined the link between hypnotic response and the personality trait of transliminality (which is underpinned, for example, by magical ideation, mystical experience, fantasy proneness, absorption, hyperaesthesia). In order to further understand the correlates of suggestibility, the aim of the current project was to investigate whether transliminality is associated with hypnotic and imaginative suggestibility (considering: objective response, subjective response and involuntariness). Another aim was to assess the contribution of transliminality as a predictor of suggestibility when a range of previously studied personality trait measures were considered. Participants completed: the Revised Transliminality Scale, Tellegen Absorption Scale, Creative Experiences Questionnaire, and the Dissociative Experiences Scale II. To avoid context effects, where knowledge or measurement of one trait or ability might influence measurement of another, a separate standalone study was conducted where hypnotic and imaginative (without hypnosis) suggestibility screenings were carried out in-person in small groups using the modified Carleton University Responsiveness to Suggestion Scale. The merging of these two datasets enabled the analyses. Transliminality was weakly correlated with the imaginative suggestibility subjective response measure (r = 0.19). Likewise, weak correlations were found between transliminality and the hypnotic suggestibility response measures (objective, r = 0.21, subjective, r = 0.23, involuntariness, r = 0.24). The multiple regressions (forward selection) reflected the pattern of correlations, with no model for any of the variables, retaining more than a single significant predictor. In summary, this study combination, avoiding context effects, shows transliminality to be a weak predictor of response to suggestion.

Minority Stress and Psychosocial Influences on Cognitive Performance in Sexual Minority Older Adults.

Background and Objectives: Sexual minorities experience health inequalities, but little is known about differences in neurocognitive health between heterosexual and sexual minority older adults and potential risk factors. To investigate minority stress, depression, and marital status as risk factors for worse cognitive performance in sexual minority older adults. Research Design and Methods: A total of 336 sexual minorities and 5,561 heterosexual participants aged 50+, noninstitutionalized, and free from neurodegenerative diseases from Wave 6 of the English Longitudinal Study of Ageing were included. Cognitive performance (i.e., temporal orientation, episodic memory, and fluid intelligence) of sexual minority and heterosexual older adults was compared using general linear models including age, sex, and education as covariates. The differential impact of minority stress, depressive symptoms, and marital status on cognition in the 2 groups were also tested. Analyses were weighted for sampling probability and differential nonresponse. Results: Sexual minority participants were more likely to report minority stress and to be single but had better episodic memory than heterosexual participants. Depression and being single were associated with worse cognitive performance in both groups. However, minority stress was negatively associated (B = -2.116, p = .016) with fluid intelligence in the sexual minority group only. Discussion and Implications: Better memory in sexual minority participants and a negative effect of risk factors on cognition are in line with previous studies. However, this study provides the first evidence of a potential negative impact of minority stress on cognitive performance in sexual minorities. Further investigations are needed to assess minority stress more in detail and clarify its potential mechanisms of action on cognition in sexual minorities.

Resting-state functional connectivity is modulated by cognitive reserve in early Parkinson's disease.

Background: Fronto-striatal disconnection is thought to be at the basis of dysexecutive symptoms in patients with Parkinson's disease (PD). Multiple reserve-related processes may offer resilience against functional decline. Among these, cognitive reserve (CR) refers to the adaptability of cognitive processes. Objective: To test the hypothesis that functional connectivity of pathways associated with executive dysfunction in PD is modulated by CR. Methods: Twenty-six PD patients and 24 controls underwent resting-state functional magnetic resonance imaging. Functional connectivity was explored with independent component analysis and seed-based approaches. The following networks were selected from the outcome of the independent component analysis: default-mode (DMN), left and right fronto-parietal (l/rFPN), salience (SalN), sensorimotor (SMN), and occipital visual (OVN). Seed regions were selected in the substantia nigra and in the dorsolateral and ventromedial prefrontal cortex for the assessment of seed-based functional connectivity maps. Educational and occupational attainments were used as CR proxies. Results: Compared with their counterparts with high CR, PD individuals with low CR had reduced posterior DMN functional connectivity in the anterior cingulate and basal ganglia, and bilaterally reduced connectivity in fronto-parietal regions within the networks defined by the dorsolateral and ventrolateral prefrontal seeds. Hyper-connectivity was detected within medial prefrontal regions when comparing low-CR PD with low-CR controls. Conclusion: CR may exert a modulatory effect on functional connectivity in basal ganglia and executive-attentional fronto-parietal networks. In PD patients with low CR, attentional control networks seem to be downregulated, whereas higher recruitment of medial frontal regions suggests compensation via an upregulation mechanism. This upregulation might contribute to maintaining efficient cognitive functioning when posterior cortical function is progressively reduced.

Associations between Neuropsychiatric Symptoms and Alzheimer's Disease Biomarkers in People with Mild Cognitive Impairment.

BACKGROUND: Neuropsychiatric symptoms (NPS) are associated with faster decline in mild cognitive impairment (MCI). This study aimed to investigate the association between NPS severity and Alzheimer's disease (AD) biomarkers, i.e., amyloid-ß (Aß), phosphorylated tau protein (p-tau) and hippocampal volume ratio (HR), to characterise in more detail MCI patients with a poor prognosis. METHODS: A total of 506 individuals with MCI and 99 cognitively unimpaired older adults were selected from the ADNI dataset. The patients were divided into three different groups based on their NPI-Q total scores: no NPS (n = 198), mild NPS (n = 160) and severe NPS (n = 148). Regression models were used to assess the association between the severity of NPS and each biomarker level and positivity status. RESULTS: Cerebrospinal fluid Aß levels were positively associated with older age and lower MMSE scores, while higher p-tau levels were associated with female sex and lower MMSE scores. Only patients with severe NPS had a lower HR (ß = -0.18, p = 0.050), i.e., more pronounced medio-temporal atrophy, than those without NPS. DISCUSSION: Only HR was associated with the presence of NPS, partially in line with previous evidence showing that severe NPS may be explained primarily by greater grey matter loss. Future longitudinal studies will be needed to ascertain the relevance of this finding.

The effect of physical activity on white matter integrity in aging and prodromal to mild Alzheimer's disease with vascular comorbidity.

Background: Physical activity is a modifiable lifestyle factor that has been previously associated with reduced vascular burden and reduced risk of dementia. Objectives: This study tested whether physical activity (i.e., being inactive vs. active) contributed to preservation of white matter microstructure in healthy aging controls and patients in prodromal to mild Alzheimer's disease with low/high vascular burden. Materials: A total of 213 participants were recruited from memory clinics. They were classified as being either physically active (n = 113) or inactive (n = 100) based on the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) questionnaire. Diffusion-weighted images were acquired for all participants and pre-processed based on a standard protocol. Methods: A factorial design using voxel-wise tract-based spatial statistics (TBSS) was adopted, with 5,000 permutations and threshold-free cluster enhancement (TFCE), to identify significant clusters for fractional anisotropy (FA), axial diffusivity (AxD), mean diffusivity (MD), and radial diffusivity (RD). Results: Clusters of higher FA and lower AxD, MD, and RD values were found for physically active compared with inactive participants that were widespread covering mainly association and projection tracts but also some commissural tracts. A three-way Group × Physical Activity × Vascular Burden interaction effect was found for FA mostly in a variety of projection tracts with a right predominance, and some commissural and association tracts. Post hoc analyses revealed higher FA in patients with high vascular burden who were physically active compared with those patients with high vascular burden who were inactive mainly in projection and association/limbic tracts with a right predominance. Additionally, higher FA was observed in physically active patients with high vascular burden as compared with physically inactive controls with high vascular burden, mainly in bilateral projection fibers and cerebellar regions. Conclusion: Voxel-wise TBSS analysis revealed better preservation of white matter microstructure that was prominent in the high-risk group such as the patients with high vascular burden, specifically those who were physically active. The beneficial effects of physical activity on white matter microstructure were not observed in the controls.

Sex differences in olfactory cortex neuronal loss in aging.

Introduction: Aging plays a major role in neurodegenerative disorders such as Alzheimer's disease, and impacts neuronal loss. Olfactory dysfunction can be an early alteration heralding the presence of a neurodegenerative disorder in aging. Studying alterations in olfaction-related brain regions might help detection of neurodegenerative diseases at an earlier stage as well as protect individuals from any danger caused by loss of sense of smell. Objective: To assess the effect of age and sex on olfactory cortex volume in cognitively healthy participants. Method: Neurologically healthy participants were divided in three groups based on their age: young (20-35 years; n = 53), middle-aged (36-65 years; n = 66) and older (66-85 years; n = 95). T1-weighted MRI scans acquired at 1.5 T were processed using SPM12. Smoothed images were used to extract the volume of olfactory cortex regions. Results: ANCOVA analyses showed significant differences in volume between age groups in the olfactory cortex (p ≤ 0.0001). In women, neuronal loss started earlier than in men (in the 4th decade of life), while in men more substantial neuronal loss in olfactory cortex regions was detected only later in life. Conclusion: Data indicate that age-related reduction in the volume of the olfactory cortex starts earlier in women than in men. The findings suggest that volume changes in olfaction-related brain regions in the aging population deserve further attention as potential proxies of increased risk of neurodegenerative diseases.

Current Understanding of Verbal Fluency in Alzheimer's Disease: Evidence to Date.

Since their development, verbal fluency tests (VFTs) have been used extensively throughout research and in clinical settings to assess a variety of cognitive functions in diverse populations. In Alzheimer's disease (AD), these tasks have proven particularly valuable in identifying the earliest forms of cognitive decline in semantic processing and have been shown to relate specifically to brain regions associated with the initial stages of pathological change. In recent years, researchers have developed more nuanced techniques to evaluate verbal fluency performance, extracting a wide range of cognitive metrics from these simple neuropsychological tests. Such novel techniques allow for a more detailed exploration of the cognitive processes underlying successful task performance beyond the raw test score. The versatility of VFTs and the richness of data they may provide, in light of their low cost and speed of administration, therefore, highlight their potential value both in future research as outcome measures for clinical trials and in a clinical setting as a screening measure for early detection of neurodegenerative diseases.

Item-Level Scores on the Boston Naming Test as an Independent Predictor of Perirhinal Volume in Individuals with Mild Cognitive Impairment.

We explored the methodological value of an item-level scoring procedure applied to the Boston Naming Test (BNT), and the extent to which this scoring approach predicts grey matter (GM) variability in regions that sustain semantic memory. Twenty-seven BNT items administered as part of the Alzheimer's Disease Neuroimaging Initiative were scored according to their "sensorimotor interaction" (SMI) value. Quantitative scores (i.e., the count of correctly named items) and qualitative scores (i.e., the average of SMI scores for correctly named items) were used as independent predictors of neuroanatomical GM maps in two sub-cohorts of 197 healthy adults and 350 mild cognitive impairment (MCI) participants. Quantitative scores predicted clusters of temporal and mediotemporal GM in both sub-cohorts. After accounting for quantitative scores, the qualitative scores predicted mediotemporal GM clusters in the MCI sub-cohort; clusters extended to the anterior parahippocampal gyrus and encompassed the perirhinal cortex. This was confirmed by a significant yet modest association between qualitative scores and region-of-interest-informed perirhinal volumes extracted post hoc. Item-level scoring of BNT performance provides complementary information to standard quantitative scores. The concurrent use of quantitative and qualitative scores may help profile lexical-semantic access more precisely, and might help detect changes in semantic memory that are typical of early-stage Alzheimer's disease.

Accelerated atrophy in dopaminergic targets and medial temporo-parietal regions precedes the onset of delusions in patients with Alzheimer's disease.

People with Alzheimer's disease (AD) and delusions have worse quality of life and prognosis. However, early markers of delusions have not been identified yet. The present study investigated whether there are any detectable differences in grey matter (GM) volume and cognitive changes in the year before symptom onset between patients with AD who did and did not develop delusions. Two matched samples of AD patients, 63 who did (PT-D) and 63 who did not develop delusions (PT-ND) over 1 year, were identified from the Alzheimer's Disease Neuroimaging Initiative database. The Neuropsychiatric Inventory (NPI) was used to assess the presence of delusions. Sixty-three additional matched healthy controls (HC) were selected. Repeated-measures ANCOVA models were used to investigate group-by-time effects on the volume of selected GM regions of interest and on cognitive performance. No neurocognitive differences were observed between patient groups prior to symptom onset. Greater episodic memory decline and GM loss in bilateral caudate nuclei, medio-temporal and midline cingulo-parietal regions were found in the PT-D compared with the PT-ND group. A pattern of faster GM loss in brain areas typically affected by AD and in cortical and subcortical targets of dopaminergic pathways, paralleled by worsening of episodic memory and behavioural symptoms, may explain the emergence of delusions in patients with AD.

The neural signatures of psychoses in Alzheimer's disease: a neuroimaging genetics approach.

Psychoses in Alzheimer's disease (AD) are associated with worse prognosis. Genetic vulnerability for schizophrenia (SCZ) may drive AD-related psychoses, yet its impact on brain constituents is still unknown. This study aimed to investigate the association between polygenic risk scores (PRSs) for SCZ and psychotic experiences (PE) and grey matter (GM) volume in patients with AD with (AD-PS) and without (AD-NP) psychosis. Clinical, genetic and T1-weighted MRI data for 800 participants were extracted from the ADNI database: 203 healthy controls, 121 AD-PS and 476 AD-NP. PRSs were calculated using a Bayesian approach and analysed at ten p-value thresholds. Standard voxel-based morphometry was used to process MRI data. Logistic regression models including both PRSs for SCZ and PE, and an AD-PRS were used to predict psychosis in AD. Associations between PRSs and GM volume were investigated in the whole sample and the three groups independently. Only the AD-PRS predicted psychosis in AD. Inconsistent associations between the SCZ-PRS and PE-PRS and GM volumes were found across groups. The SCZ-PRS was negatively associated with medio-temporal/subcortical volumes and positively with medial/orbitofrontal volumes in the AD-PS group. Only medio-temporal areas were more atrophic in the AD-PS group, while there was no significant correlation between psychosis severity and GM volume. Although not associated with psychoses, the SCZ-PRS was correlated with smaller medio-temporal and larger orbitofrontal volumes in AD-PS. Similar alterations have also been observed in SCZ patients. This finding suggest a possible disconnection between these regions associated with psychoses in more advanced AD.

Verbal fluency discrepancies as a marker of the prehippocampal stages of Alzheimer's disease.

OBJECTIVE: Prior to evidence of episodic memory decline, a lengthy preclinical phase of Alzheimer's disease (AD) exists characterized by the build-up of tau pathology within extrahippocampal structures. Semantic memory, also impaired in AD, has been linked to degradation within these earliest affected areas. This study aimed to assess the utility of performance discrepancies between letter and category verbal fluency tasks to detect neuronal loss in brain regions affected very early by AD. METHOD: Whole-brain voxel-based morphometry was used to assess the neural correlates of semantic processing in three patient groups: two groups of mild cognitive impairment (MCI) patients split into mildly (n = 58) and moderately (n = 53) affected and a mild AD dementia group (n = 71). Discrepancies between the level of impairment on the semantic category fluency test and nonsemantic letter fluency test were calculated for each participant and included in regression models measuring the relationship between semantic memory and whole-brain gray matter volume. RESULTS: Patients at all disease stages demonstrated a loss of the normal semantic advantage in fluency tests, showing significantly greater impairments in category relative to letter fluency. Discrepancy scores in mild MCI correlated strongly with the structural integrity of the anterior medial temporal lobes. Correlations in more severely affected groups were weaker and more widespread. CONCLUSIONS: Semantic memory appears a useful indicator of even the earliest stages of medial temporal damage in AD. With advancing disease severity, the discrepancy index loses its focal anatomical association, reinforcing its value as an early marker of incipient decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Macrostructural and Microstructural White Matter Alterations Are Associated with Apathy across the Clinical Alzheimer's Disease Spectrum.

Apathy is the commonest neuropsychiatric symptom in Alzheimer's disease (AD). Previous findings suggest that apathy is caused by a communication breakdown between functional neural networks involved in motivational-affective processing. This study investigated the relationship between white matter (WM) damage and apathy in AD. Sixty-one patients with apathy (AP-PT) and 61 without apathy (NA-PT) were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and matched for cognitive status, age and education. Sixty-one cognitively unimpaired (CU) participants were also included as controls. Data on cognitive performance, cerebrospinal fluid biomarkers, brain/WM hyperintensity volumes and diffusion tensor imaging indices were compared across groups. No neurocognitive differences were found between patient groups, but the AP-PT group had more severe neuropsychiatric symptoms. Compared with CU participants, only apathetic patients had deficits on the Clock Drawing Test. AP-PT had increased WM damage, both macrostructurally, i.e., larger WM hyperintensity volume, and microstructurally, i.e., increased radial/axial diffusivity and reduced fractional anisotropy in the fornix, cingulum, anterior thalamic radiations and superior longitudinal and uncinate fasciculi. AP-PT showed signs of extensive WM damage, especially in associative tracts in the frontal lobes, fornix and cingulum. Disruption in structural connectivity might affect crucial functional inter-network communication, resulting in motivational deficits and worse cognitive decline.

A Multimodal Neuroimaging and Neuropsychological Study of Visual Hallucinations in Alzheimer's Disease.

BACKGROUND: Hallucinations in Alzheimer's disease (AD) have been linked to more severe cognitive and functional decline. However, research on visual hallucinations (VH), the most common type of hallucinations in AD, is limited. OBJECTIVE: To investigate the cognitive and cerebral macrostructural and metabolic features associated with VH in AD. METHODS: Twenty-four AD patients with VH, 24 with no VH (NVH), and 24 cognitively normal (CN) matched controls were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Differences in regional gray matter (GM) volumes and cognitive performance were investigated with whole brain voxel-based morphometry analyses of MRI structural brain scans, and analyses of neuropsychological tests. Glucose metabolic changes were explored in a sub-sample of patients who had FDG-PET scans available. RESULTS: More severe visuoconstructive and attentional deficits were found in AD VH compared with NVH. GM atrophy and hypometabolism were detected in occipital and temporal areas in VH patients in comparison with CN. On the other hand, NVH patients had atrophy and hypometabolism mainly in temporal areas. No differences in GM volume and glucose metabolism were found in the direct comparison between AD VH and NVH. CONCLUSION: In addition to the pattern of brain abnormalities typical of AD, occipital alterations were observed in patients with VH compared with CN. More severe visuoconstructive and attentional deficits were found in AD VH when directly compared with NVH, and might contribute to the emergence of VH in AD.

The Impact of Social Isolation Due to COVID-19 on Symptom Progression in People With Dementia: Findings of the SOLITUDE Study.

Background: People with dementia (PWD) are vulnerable to abrupt changes to daily routines. The lockdown enforced on the 23rd of March 2020 in the UK to contain the expansion of the COVID-19 pandemic limited opportunities for PWD to access healthcare services and socialise. The SOLITUDE study explored the potential long-term effects of lockdown on PWD's symptoms and carers' burden. Methods: Forty-five carers and 36 PWD completed a telephone-based assessment at recruitment (T0) and after 3 (T1) and 6 months (T2). PWD completed measures validated for telephonic evaluations of cognition and depression. Carers completed questionnaires on their burden and on PWD's health and answered a customised interview on symptom changes observed in the initial months of lockdown. Longitudinal changes were investigated for all outcome variables with repeated-measures models. Additional post hoc multiple regression analyses were carried out to investigate whether several objective factors (i.e., demographics and time under social restrictions) and carer-reported symptom changes observed following lockdown before T0 were associated with all outcomes at T0. Results: No significant changes were observed in any outcomes over the 6 months of observations. However, post hoc analyses showed that the length of social isolation before T0 was negatively correlated with episodic and semantic memory performance at T0. Carers reporting worsening of neuropsychiatric symptoms and faster disease progression in PWD also reported higher burden. Moreover, carer-reported worsening of cognitive symptoms was associated with poorer semantic memory at T0. Conclusion: PWD's symptoms and carers' burden remained stable over 6 months of observation. However, the amount of time spent under social restrictions before T0 appears to have had a significant detrimental impact on cognitive performance of patients. In fact, carer-reported cognitive decline during social isolation was consistent with the finding of poorer semantic memory, a domain sensitive to progression in Alzheimer's disease. Therefore, the initial stricter period of social isolation had greater detrimental impact on patients and their carers, followed then by a plateau. Future interventions may be designed to maintain an optimal level of social and cognitive engagement for PWD in challenging times, to prevent abrupt worsening of symptoms and associated detrimental consequences on patients' carers.

The impact of social isolation due to the COVID-19 pandemic on patients with dementia and caregivers.

OBJECTIVE: Social distancing to limit COVID-19 transmission has led to extensive lifestyle changes, including for people with dementia (PWD). The aim of this study, therefore, was to assess the impact of lockdown on the mental health of PWD and their carers. METHODS: Forty-five carers of PWD completed a telephone interview during the baseline assessment of the SOLITUDE study to gather information on life conditions and changes in symptoms of PWD during lockdown. Associations between changes in symptoms of PWD and carers' concerns and mental health were investigated. RESULTS: About 44% of carers experienced anxiety and irritability and reported changes in behavioural and cognitive symptoms in PWD. These changes were associated with worse carers' mental health and concerns about faster disease progression (χ2 = 13.542, p < 0.001). CONCLUSION: COVID-19-related social isolation has had a negative impact on patients' and carers' mental health. Potential long-term neurocognitive consequences require further investigation.