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.

Assessing the pool activity level (PAL) checklist for use with people with hearing and vision loss.

BACKGROUND: The PAL is a career-completed assessment that indexes cognitive functional ability to inform individualised support. As hearing and vision loss are prevalent, we assessed the PAL for potential bias with hearing or vision impairment. METHODS: We collected PAL responses for 333 adults aged over 60 years in the UK, France, Canada, Greece and Cyprus. All participants had normal cognition based on self-reported status and normal range scores on a cognitive screening test. Using a Kruskal-Wallis test, we compared PAL item response distributions for people with assessed hearing or vision loss compared to those with normal sensory function. RESULTS: There were no differences in response distributions between hearing or vision impaired groups versus those with normal sensory function on any PAL item. CONCLUSION: The PAL reliably indexes cognitive functional ability and may be used to inform support tailored to individual cognitive level amongst older adults with prevalent hearing and vision impairments.

Care burden, loneliness, and social isolation in caregivers of people with physical and brain health conditions in English-speaking regions: Before and during the COVID-19 pandemic.

BACKGROUND: Public health restrictions due to the COVID-19 (SARS CoV-2) pandemic have disproportionately affected informal caregivers of people living with long term health conditions. We aimed to explore levels of care burden, loneliness, and social isolation among caregivers of people with enduring physical and brain health conditions in English-speaking regions worldwide, by investigating outcomes before and during the COVID-19 pandemic. METHODS: A cross-sectional anonymous online survey data from 2287 English-speaking caregivers of people with long term health conditions from four English-speaking regions (UK, Ireland, USA, New Zealand) included measures of care burden, loneliness, and social isolation, reported before and during the COVID-19 pandemic. Analyses were descriptive, followed by an ordinal regression model for predictors of burden. RESULTS: Compared to pre-pandemic levels, all caregivers experienced a significant increase in burden, loneliness, and isolation. Caregivers of people with both brain health and physical conditions were the most burdened and had the highest levels of loneliness and isolation compared to caregivers of people with either a brain health or physical condition only. The increase in care burden among caregivers of people with brain health challenges was associated with caregiver's gender, moderate and severe emotional loneliness, magnitude and frequency of isolation during the pandemic, and care circumstances (cohabitation with the care recipient, restrictions on the ability to provide care). CONCLUSIONS: Health and social care interventions should target caregivers' care circumstances and psychological outcomes, particularly in women, accounting for the significant additional burden of care, loneliness, and isolation resulting from pandemic-related restrictions.

Reporting of outcomes and measures in studies of interventions to prevent and/or treat delirium in older adults resident in long-term care: a systematic review.

OBJECTIVES: to inform development of a core outcome set, we evaluated outcomes, definitions, measures and measurement time points in clinical trials of interventions to prevent and/or treat delirium in older adults resident in long-term care (LTC). DATA SOURCES: we searched electronic databases, systematic review repositories and trial registries (1980 to 10 December 2021). STUDY SELECTION AND DATA EXTRACTION: we included randomised, quasi-randomised and non-randomised intervention studies. We extracted data on study characteristics, outcomes and measurement features. We assessed outcome reporting quality using the MOMENT study scoring system. We categorised outcomes using the Core Outcome Measures in Effectiveness Trials taxonomy. DATA SYNTHESIS: we identified 18 studies recruiting 5,639 participants. All evaluated non-pharmacological interventions; most (16 studies, 89%) addressed delirium prevention. We identified 12 delirium-specific outcomes (mean [SD] 2.4 [1.5] per study), of which delirium incidence (14 studies, 78%) and severity (6 studies, 33%) were most common. We found heterogeneity in description of outcomes and measurement time points. The Confusion Assessment Method (three versions) was the most common measure used to ascertain delirium incidence (7 of 14 studies, 50%). We identified 25 non-delirium specific outcomes (mean [SD] 4.0 [2.3] per study), with hospital admission the most commonly reported (9 studies, 50%). CONCLUSIONS: we identified few studies of interventions for the prevention or treatment of delirium in older adults resident in LTC. These studies were heterogeneous in the outcomes reported and measures used. These data inform the consensus-building stage of a core outcome set.

Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis.

BACKGROUND: Delirium is common and distressing for patients receiving palliative care. Interventions targetting modifiable risk factors in other settings have been shown to prevent delirium. Research on delirium risk factors in palliative care can inform context-specific risk-reduction interventions. AIM: To investigate risk factors for the development of delirium in adult patients receiving specialist palliative care. DESIGN: Systematic review and meta-analysis (PROSPERO CRD42019157168). DATA SOURCES: CINAHL, Cochrane Database of Systematic Reviews, Embase, MEDLINE and PsycINFO (1980-2021) were searched for studies reporting the association of risk factors with delirium incidence/prevalence for patients receiving specialist palliative care. Study risk of bias and certainty of evidence for each risk factor were assessed. RESULTS: Of 28 included studies, 16 conducted only univariate analysis, 12 conducted multivariate analysis. The evidence for delirium risk factors was limited with low to very low certainty. POTENTIALLY MODIFIABLE RISK FACTORS: Opioids and lower performance status were positively associated with delirium, with some evidence also for dehydration, hypoxaemia, sleep disturbance, liver dysfunction and infection. Mixed, or very limited, evidence was found for some factors targetted in multicomponent prevention interventions: sensory impairments, mobility, catheter use, polypharmacy (single study), pain, constipation, nutrition (mixed evidence). NON-MODIFIABLE RISK FACTORS: Older age, male sex, primary brain cancer or brain metastases and lung cancer were positively associated with delirium. CONCLUSIONS: Findings may usefully inform interventions to reduce delirium risk but more high quality prospective cohort studies are required to enable greater certainty about associations of different risk factors with delirium during specialist palliative care.

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.

The Characteristics and Outcomes of People with Dementia in Inpatient Mental Health Care: A Review.

OBJECTIVES: Inpatient mental health beds for people with dementia are a limited resource. Practitioners need an understanding of this population to provide high-quality care and design services. This review examines the characteristics, care, and outcomes of people with dementia admitted to inpatient mental health services. METHODS: Systematic searches of key databases were undertaken up to November 2021. Findings were grouped into categories and then synthesized into a narrative review. RESULTS: The review identified 36 international papers, the majority of which were retrospective audits. The literature describes significant psychiatric and medical comorbidity and significant risk of change in residence and death associated with admission. CONCLUSIONS: We found a limited literature describing the characteristics, care, and outcomes of people with dementia in inpatient mental health services. The lack of research is striking given the complexity and vulnerability of this client group. More research is needed to describe the needs of this group, current and best practice to optimize care. CLINICAL IMPLICATIONS: Professionals working in inpatient mental health services need to be aware of the evidence base available, consider how they evaluate patient outcomes, review their staffing and skills mix, and seek the views of patients and relatives in improving services.

Hearing and vision health for people with dementia in residential long term care: Knowledge, attitudes and practice in England, South Korea, India, Greece, Indonesia and Australia.

OBJECTIVES: Up to 90% of people with dementia in long term care (LTC) have hearing and/or vision impairment. Hearing/vision difficulties are frequently under-recognised or incompletely managed. The impacts of hearing/vision impairment include more rapid cognitive decline, behavioural disturbances, reduced quality of life, and greater care burden. This research investigated LTC staff knowledge, attitudes and practice regarding hearing/vision care needs for residents with dementia. METHODS: A survey of staff in LTC facilities in England, South Korea, India, Greece, Indonesia and Australia. Respondents used a five-point scale to indicate agreement or YES/NO response to questions regarding sensory-cognitive care knowledge (what is known); attitudes (what is thought); practice (what is done). RESULTS: Respondents reported high awareness of hearing/vision care needs, although awareness of how to identify hearing/vison difficulties or refer for assessment was low. Most felt that residents were not able to use hearing/vision devices effectively due to poor fit, being poorly tolerated or lost or broken devices. A substantial minority of respondents reported low confidence in supporting use of assistive hearing/vision devices, with lack of training the main reason. Most staff did not undertake routine checking of hearing/vision devices, and it was rare for facilities to have designated staff responsible for sensory needs. Variation among countries was not significant after accounting for staff experience and having received dementia training. CONCLUSIONS: There is a need to improve sensory support for people with dementia in LTC facilities internationally. Practice guidelines and training to enhance sensory-cognitive knowledge, attitudes and practice in professional care teams is called for.

Visual hallucinations in neurological and ophthalmological disease: pathophysiology and management.

Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson's disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. The National Institute for Health Research (NIHR) funded a research programme to investigate visual hallucinations in the key and high burden areas of eye disease, dementia and Parkinson's disease, culminating in a workshop to develop a unified framework for their clinical management. Here we summarise the evidence base, current practice and consensus guidelines that emerged from the workshop.Irrespective of clinical condition, case ascertainment strategies are required to overcome reporting stigma. Once hallucinations are identified, physical, cognitive and ophthalmological health should be reviewed, with education and self-help techniques provided. Not all hallucinations require intervention but for those that are clinically significant, current evidence supports pharmacological modification of cholinergic, GABAergic, serotonergic or dopaminergic systems, or reduction of cortical excitability. A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations.

Cognitive impairment and Charles Bonnet syndrome: a prospective study.

OBJECTIVES: Charles Bonnet syndrome (CBS) is a common cause of visual hallucinations in older people. The relationship between CBS and cognitive impairment is unclear, but anecdotal reports exist of dementia emerging in patients diagnosed with CBS. This work set out to determine if there is an increased incidence of dementia, and increased severity of cognitive impairment, in people with CBS compared to controls from the same clinical setting. METHOD: People over 65 attending low-vision and glaucoma clinics, and a cohort of age-matched controls, underwent a psychiatric assessment. The cohorts were followed up after one year. RESULTS: Mild cognitive impairment was present in 2/12 CBS participants and 2/10 controls. Partial insight was seen in nine CBS participants. Two participants with CBS, and no controls, developed dementia at follow-up. No significant differences in performance on the ACE-R were found between the groups. Both participants who developed dementia had partial insight and hallucinations of familiar figures at diagnosis of CBS, and one had mild cognitive impairment. CONCLUSIONS: Reassurance that CBS is universally benign may be misplaced. Some people given this diagnosis go on to develop dementia. Cognitive testing at the point of diagnosis was unable to identify those at risk of this outcome. Partial insight, the presence of Mild Cognitive Impairment, and hallucinations of familiar figures at diagnosis of CBS may confer an increased risk of subsequent dementia diagnosis. Copyright © 2017 John Wiley & Sons, Ltd.

Charles Bonnet syndrome and cognitive impairment: a systematic review.

ABSTRACT Background: Charles Bonnet syndrome (CBS) is defined as complex persistent visual hallucinations in the absence of mental disorder. It is common in conditions causing significant visual impairment. Many authors advise reassurance, considering the condition benign. However, others have suggested that CBS may in some patients represent the early stages of dementia. This review seeks to systematically examine the evidence for any link between CBS and cognitive impairment. Methods: Literature search using OVID Medline, PsychINFO, and Embase. Results: Three studies where cognitive functioning was the primary focus of the research were found. All were small, did not properly apply diagnostic criteria, and reported conflicting results. Eight other studies commented on cognitive functioning, but none used tests sufficiently sensitive to detect changes seen in early dementia. One hundred and thirty four case reports were scrutinized, and reports found of 16 patients with CBS where dementia emerged. High rates of partial insight at diagnosis of CBS were seen in these patients. Conclusions: There have been no adequately powered studies, using accepted diagnostic criteria, where changes in cognitive functioning were the primary outcome. Existing studies are of limited methodological quality and allow no conclusion regarding a relationship between cognitive impairment and CBS to be reached. Numerous case reports of dementia developing in patients with CBS and partial insight raise the possibility of a link between these conditions. There is a clear need for properly constructed studies to investigate this.

Trust and acceptability of data-driven clinical recommendations in everyday practice: A scoping review.

BACKGROUND: Increasing attention is being given to the analysis of large health datasets to derive new clinical decision support systems (CDSS). However, few data-driven CDSS are being adopted into clinical practice. Trust in these tools is believed to be fundamental for acceptance and uptake but to date little attention has been given to defining or evaluating trust in clinical settings. OBJECTIVES: A scoping review was conducted to explore how and where acceptability and trustworthiness of data-driven CDSS have been assessed from the health professional's perspective. METHODS: Medline, Embase, PsycInfo, Web of Science, Scopus, ACM Digital, IEEE Xplore and Google Scholar were searched in March 2022 using terms expanded from: "data-driven" AND "clinical decision support" AND "acceptability". Included studies focused on healthcare practitioner-facing data-driven CDSS, relating directly to clinical care. They included trust or a proxy as an outcome, or in the discussion. The preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) is followed in the reporting of this review. RESULTS: 3291 papers were screened, with 85 primary research studies eligible for inclusion. Studies covered a diverse range of clinical specialisms and intended contexts, but hypothetical systems (24) outnumbered those in clinical use (18). Twenty-five studies measured trust, via a wide variety of quantitative, qualitative and mixed methods. A further 24 discussed themes of trust without it being explicitly evaluated, and from these, themes of transparency, explainability, and supporting evidence were identified as factors influencing healthcare practitioner trust in data-driven CDSS. CONCLUSION: There is a growing body of research on data-driven CDSS, but few studies have explored stakeholder perceptions in depth, with limited focused research on trustworthiness. Further research on healthcare practitioner acceptance, including requirements for transparency and explainability, should inform clinical implementation.

Dementia in-patient units in psychiatric hospitals: research priority setting.

AIMS AND METHOD: Dementia in-patient units (DIU) are mental health wards that care for people living with dementia (PLWD) whose symptoms are causing severe distress or potential risk. DIUs look after some of the most vulnerable and unwell people in society, yet they are environments that are underresearched: a recent systematic review revealed only 36 articles worldwide relating to DIUs. To better understand research priorities in DIUs, we undertook a two-round online Delphi survey of PLWD with experience of DIUs, their carers and professionals who work in DIUs. RESULTS: Ten research priorities were described and ranked. The top three were how to use non-pharmacological techniques to manage non-cognitive symptoms of dementia, supporting families and better understanding of how to discharge PLWD safely and healthily. CLINICAL IMPLICATIONS: This is the first Delphi consensus to describe DIU research priorities. This paper will help researchers focus on the areas that matter most to people who use DIUs.

A cross-cultural study of the Montreal Cognitive Assessment for people with hearing impairment.

BACKGROUND: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long-term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA-H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA-H. METHODS: The current study investigated the performance of the MoCA-H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA-H. RESULTS: In a multiple regression model accounting for age, sex, and education, cultural-linguistic group accounted for 6.89% of variance in the total MoCA-H score. Differences between languages in mean score of up to 2.6 points were observed. CONCLUSIONS: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA-H such that optimal performance cut points for identification of cognitive impairment derived in English-speaking populations are likely inappropriate for use in non-English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA-H.

Family experiences of inpatient mental health care for people with dementia.

Introduction: This study investigates family carers experiences of inpatient mental health care for people with dementia. A mental health inpatient admission for a person with dementia is usually considered when a person is distressed and this distress leads to behaviours that are assessed to be risky for the person or others. Methods: Participants included seven family carers whose relative with dementia had been cared for within a mental health ward in the United Kingdom UK within the last 5 years. Interviews were used to explore the circumstances that led to the admission, expectations of mental health care, and perceptions of care during the admission and support received by family carers. Results: Participants described their distress at the time of admission and how the process of admission sometimes added to their distress. Carers often felt excluded from their relatives care in hospital and many felt a loss of their rights. Participants felt that the mental health admission had a negative impact on their relative with dementia. Mental health law and legislation was difficult to navigate and carers were concerned about how much knowledge and understanding of dementia staff have. Discussion: Findings suggest that family carers may benefit from targeted support during their relatives admission. Mental health wards could do more to recognise the expertise in care and knowledge of the person with dementia of family carers and involve them in planning care. More research is needed to explore the experiences and outcomes of people with dementia during such admissions.

Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA-H).

BACKGROUND: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment. METHODS: We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors. RESULTS: One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2-4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952-0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test-retest reliability was 0.92 (95%CI 0.78-0.97). CONCLUSION: The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.

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.

Sensory Health for Residents with Dementia in Care Homes in England: A Knowledge, Attitudes, and Practice Survey.

BACKGROUND: Most residents with dementia (RwD) in long-term care (LTC) facilities experience hearing and vision problems, yet these sensory deficits, which are associated with poor outcomes, are frequently under-recognized or incompletely managed. OBJECTIVE: We investigated the knowledge, attitudes, and practice (KAP) of LTC facility staff in England regarding sensory-cognitive health of RwD. DESIGN: A cross-sectional survey using self-administered online or mail-in questionnaires. SETTING AND PARTICIPANTS: The study included 117 LTC facilities throughout England, involving 887 staff of different grades (managers, n=79; nurses/allied health professionals, n=160; care workers, n=648). METHODS: Using a sampling frame of all LTC facilities nationwide, we included a stratified random selection of facilities, surveying staff regarding KAP of sensory-cognitive health. Analysis was descriptive, followed by a regression model for predictors of overall KAP capacity of staff, based on a Rasch analysis of survey items. RESULTS: Staff of all grades reported high knowledge and awareness of sensory-health concerns amongst RwD, but training opportunities were infrequent and most front-line staff felt they lacked the skills necessary to support the use of hearing and vision aids. The most reported reason for poor use of hearing aids/glasses related to lack of maintenance and care procedures (ie, broken and lost devices), and poor adherence support (ie, not tolerating the devices). Staff willingness to receive training was high. Most managers reported that training in communication skills and "sensory-friendly" environments was not provided. Finally, higher overall KAP capacity of staff was predicted by smaller facility size and public, rather than private, facility type. CONCLUSIONS AND IMPLICATIONS: Training and practice of sensory health care in RwD in LTC in England is lacking. To improve sensory-cognitive care for LTC RwD, there is a clear need for (1) practice recommendations and (2) multifaceted interventions that include staff training, tailored sensory support, and environmental modification.

Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?

BACKGROUND: Type 2 diabetes is a risk factor for Alzheimer's disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects. METHODS: In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with arterial cannula insertion for radioactivity measurement. T1 Volumetric and FLAIR sequences were acquired on a 3-T MRI scanner. These subjects also had measurement of glucose and insulin levels after a 4-h fast on the same day of the scan. Insulin resistance was calculated by the updated homeostatic model assessment (HOMA2). For [18F]FDG analysis, cerebral glucose metabolic rate (rCMRGlc) parametric images were generated using spectral analysis with arterial plasma input function. RESULTS: In this non-diabetic AD population, HOMA2 was negatively associated with hippocampal rCMRGlc, along with total grey matter volumes. No significant correlation was observed between HOMA2, hippocampal volume and WMLs. CONCLUSIONS: In non-diabetic AD, peripheral insulin resistance is independently associated with reduced hippocampal glucose metabolism and with lower grey matter volume, suggesting that peripheral insulin resistance might influence AD pathology by its action on cerebral glucose metabolism and on neurodegeneration.