Mood disorders are common psychiatric illnesses that represent a major cause of disability worldwide. With life expectancy and the percentage of elderly people rising in many developed and undeveloped countries around the globe, cognitive impairment and dementia are gaining a societal importance. The relation between mood disorders and cognitive function is a twofold. On the one hand, cognitive deficits within mood disorders have been studied extensively, in which there seems to be a persistent neurocognitive impairment, both in acute phases and in interepisodic euthymic phases. Although results have not always been consistent, an overall pattern of specific impairments – in executive function, attention and memory - has become evident. On the other hand, recent research suggests that mood disorders, in general, may be risk factors for the development of mild cognitive impairment and dementia. In this sense, of the many models for the association of mood disorders and dementia, two are favored by several authors. One suggests that mood disorders are a risk factor for earlier clinical manifestation of dementia. The second sees mood disorders as the cause of dementing states, for instance through neuronal loss via dysregulation of the glucocorticoid cascade. In fact, there is suggestion that impairment of neuroplasticity may underlie the pathophysiology of mood disorders as such, and not only of neurocognitive impairment. In some patients, specific neurocognitive functions may be present before the onset of mood disorder and may constitute a trait factor or even an endophenotype. The aim of the present work is to, through a basic narrative review of published research on the main databases, summarize the main evidences of the association of mood disorders and dementia.

Objective: To present an atypical clinical case and to review the literature on frontotemporal dementia (FTD) focusing on the most frequent psychopathological findings.

Methods: Case report and a non systematic review using databases Pubmed, UpToDate, Medscape, between 2007 to 2020. Keywords: frontotemporal dementia, psychiatry, psychopathology.

Results: FTD is a neurodegenerative syndrome that appears most frequently in the fifth and sixth decades, mostly before the age of 65. Six to seven years before the diagnosis of FTD, psychiatric disorders such as major depression can appear. The behavioral variant DFT is characterized by symptoms such as disinhibition, apathy or inertia, loss of empathy, hyperorality, persevering behaviors, executive dysfunction, and it is also associated with changes in imaging exams, namely frontal and temporal cortical atrophy, which may affect one or both hemispheres. We present the case of a 66-year-old female patient, accompanied for a long time in psychiatry by conversion and dissociative symptoms, associated with histrionic personality traits. She was hospitalized for deteriorating functioning, pauted by great agitation and maladjusted behavior, alteration of thought and speech, and marked perseverance, as well as periods of space-time disorientation. Analytically, there were no changes, as well as in imaging exams such as CT and MRI. It was performed an electroencephalogram (EEG) that demonstrated diffuse cortical dysfunction.

Discussion/Conclusion: This case is atypical in the DFT pattern, regarding the age of onset and the absence of imaging findings. However, there was alterations in the EEG, which together with the symptomatic presentation point to DFT. This case exemplifies the difficulty in the management of symptoms, whose therapy is purely symptomatic and psychoeducational strategies for the family and caregivers are fundamental.

Visual Hallucinations (VH) are a common psychiatric symptom of Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). According to the Perception-Attention Deficits Model, VH stem from impaired perceptual (bottom-up), including dorsal (DVS) and ventral visual streams (VVS), and attentional (top-down) processes, with a persistent Default Mode Network (DMN) activity and a dysfunctional imbalance of Dorsal (DAN) and Ventral Attentional Networks (VAN).

We review the literature on the neurobiological underpinnings of VH in DLB and PD, concerning overlapping and different mechanisms.

In DLB hallucinators, PET-scan findings of disconnection between higher and primary visual areas and dysfunctional recruitment of the VVS, corroborate other imaging and neuropathologic studies which document inferior longitudinal fasciculus damage and increased temporal lobe Lewy body (LB) pathology. The alteration of network topography is more pronounced in the DAN and DMN. The involvement of anterior cortical regions, clustering around attentional networks, is demonstrated in neuropathologic, volumetric and perfusion studies. VH severity closely correlates with anterior cingulate cortex and inferior temporal cortex hypoperfusion, structural changes in the DVS (superior parietal gyrus and precuneus) and increased diffusivity of the right thalamic projections to parieto-occipital cortices. Thalamocortical dysfunction alongside decreased cholinergic activity in reticular nucleus, which receive projections from the nucleus basalis of Meynert, seems to play a crucial role.

Both DLB and demented PD hallucinators have more frontal cortical atrophy, yet greater in DLB, supporting top-down mechanisms.

Regarding PD hallucinators, findings of cortical atrophy in inferior parietal lobule, cuneus, lingual lobule, and precentral gyrus correlated with hallucination scores. However, some studies did not evidence volumetric cortical differences between hallucinators and non-hallucinators. Moreover, LB are not necessarily present in hallucinators, suggesting other neuropathologic mechanisms in the genesis of VH, namely altered neurochemical circuitry. Volume loss in pedunculopontine nucleus and right-thalamus support the hypothesis of a dysfunctional cholinergic brainstem control of the cortex. PET-scan studies discovered higher 5-HT2A receptor levels in the inferolateral temporal and prefrontal cortices. A greater nigrostriatal impairment is documented in the right-caudate of hallucinators. Therefore, VH may arise from an inability to activate DAN (in which caudate is involved) and consequent faulty visuo-perceptual processing by DMN and VAN.

Objectives: More and more referrals to memory clinics are expected, but diagnostic routes are already challenged. In order to be able to follow the advice to diagnose dementia more often and earlier in the process, but also to be able to handle the increasing numbers of referrals, a fast but reliable triage test is needed.

According to the Cochrane review, “the MoCA can help identify people who need specialist assessment and treatment for dementia”. It has been validated in multiple institutions and languages. However, many of these studies are designed with a case-control design using healthy, community-based individuals as controls, which can lead to spectrum bias.

Our cohort of referrals to a memory clinic with patients suspected of having cognitive disorders (mild dementia and MCI) after initial assessment in an old age psychiatric clinic, needs to be validated because different settings can give different results.

Design: our reference standard consisted of a consensus-based diagnosis according to international criteria for detecting MCI and MD, and this was compared with patients suspected of MCI/MD - but excluded from cognitive disorders (NoCI)- from the same cohort.

Results: The mean MoCA scores differ significantly between the groups: 24 in NoCI, 21 in MCI and 16.5 in MD. The AUC of MD against non-demented (MCI+NoCI) was 0.83 resulting in 90% sensitivity, 65% specificity, 50% PPV and 94% NPV at a best cut-off of <21 according the Younden index. For CI (MD+MCI) against NoCI the results were respectively 0.77AUC, 95%sens, 47%spec, 88%PPV, 68%NPV at a cut-off <26.

On an individual basis, as a box plot of DSM IV diagnoses showed, the MoCA score has limitations and clinical aspects need to be taken into account: FTD, high education to the upside; MCI including psychiatric etiology to the downside.

Conclusions: by using a cut-off score of <21, 90% of people with positive MoCA have CI, while 94% of people with negative MoCA (≥21) will not have dementia. The MoCA can significantly reduce referrals (50%) by excluding patients for further diagnostic work-up at a memory clinic, even if they are suspected of CI after initial assessment.

Background Mild Cognitive Impairment is an at-risk stage for dementia and early detection has been increasingly recommended to facilitate beneficial interventions and forward planning. Changes in cognition and function can be insidious. In ageing populations, relying on relatives to detect changes is not sustainable. Moreover, resource scarcity necessitates that we innovate to find less manpower dependent methods for early detection and assessment.

Objectives In two separate feasibility studies, we set out to evaluate if sensors could be utilized to (1) detect changes in behaviour patterns in homes of community dwelling elderly* & (2) evaluate instrumental activities of daily living (iADLs) in a smart home lab setting.

Method In the first study, 59 community-dwelling seniors (aged >65 years) were observed over the course of 2 months through the use of motion sensors, smart plugs, bed sensors and activity bands. Behaviour metrics such as forgetfulness, outings and sleep were tracked. In the second study, a smart lab was equipped with similar sensors and 35 seniors were tasked to complete two iADLs (using the telephone and counting money) while being evaluated by the sensor system.

Results In both studies, we found that it was feasible and seniors found the sensors to be acceptable. Over 80% of seniors had positive feedback for the in-home system and over 95% of seniors had found the lab-based evaluation of iADLs to be acceptable.

Conclusion Sensor technology and smart homes are feasible to utilize for assessment and monitoring of cognition and function. Knowing that seniors find it acceptable is a crucial initial step. Much more needs to be done to refine the systems and the clinical information it yields.

Background: For the rising number of people living with dementia, cost-effective community-based interventions to support psychosocial care are needed. The FindMyApps program helps people with dementia and their caregivers learn to use tablet computers and find user-friendly apps that facilitate self-management and engagement in meaningful activities. This definitive trial builds on previous feasibility pilot trials of FindMyApps and further evaluates cost-effectiveness.

Method: This is a protocol for a non-blinded randomized controlled trial (RCT) with two arms (intervention and usual care). 150 dyads (person with dementia and their carer) will be recruited. Participants must be resident in the community, with a diagnosis of Mild Cognitive Impairment or mild dementia (Mini Mental-State Examination 17-26, or Global Deterioration Scale 3-4. Dyads will be randomly assigned in equal proportions to receive either the FindMyApps intervention (experimental arm) or usual care (control arm). Primary outcomes measured at 3 months will be: patient self-management and social participation; caregiver sense of competence. Data will be collected through questionnaires filled in by the researcher (patient outcomes) or participants themselves (carer outcomes). In addition to a main effect analysis, a cost-effectiveness analysis will take place. In line with Medical Research Council (MRC) guidance for the evaluation of complex interventions, a process analysis will be undertaken, to identify factors that may influence trial outcomes. Semi-structured interviews and remotely collected data regarding use of the FindMyApps app will support the process analysis.

Result: Results of this study are expected in 2022. The study will be adequately powered to detect at least a moderate effect size of the intervention with respect to the primary outcomes.

Conclusion: This study will investigate the effectiveness and cost-effectiveness of the FindMyApps intervention. The results of the study will provide strong evidence to support or oppose scaling up implementation of the intervention. This is also an example of how the MRC framework for the evaluation of complex interventions can be implemented in practice. In a field which is often criticized for a lack of high quality evidence, randomized controlled trials should be applied more frequently designed for the robust and transparent evaluation of digital tools and technologies.

Dementia-related psychosis (DRP) is common among patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VaD) and is associated with poor outcomes. HARMONY (NCT03325556) was a Phase 3, placebo-controlled, randomized, relapse-prevention study evaluating the efficacy and safety of pimavanserin for treating hallucinations and delusions associated with DRP. Patients with dementia and moderate-severe psychosis received open-label (OL) pimavanserin for 12 weeks. Patients with a sustained response (≥30% reduction in Scale for the Assessment of Positive Symptoms hallucinations+delusions Total Score AND Clinical Global Impression-Improvement score of much/very much improved) at Weeks 8 and 12 were randomized 1:1 to continue pimavanserin or receive placebo for up to 26 weeks in the double-blind (DB) period. The primary endpoint was time from randomization to relapse of DRP. 392 patients enrolled. 217 (61.8%) eligible patients experienced sustained response and were randomized. OL response was similar regardless of dementia subtype (randomization rates: 59.8% AD, 71.2% PDD, 71.4% VaD, 45.5% DLB, 50.0% FTD), baseline disease characteristics, age, dementia severity, or previous drug therapy. The study stopped early for superior efficacy when a prespecified interim analysis revealed >2.8-fold reduction in risk of relapse with pimavanserin (hazard ratio: 0.353; 95% CI: 0.172, 0.727; 1-sided p=0.0023). Adverse event rates were low and balanced (OL: 36.2%; DB: 41.0% pimavanserin, 36.6% placebo). No negative trends for worsening in cognition (as assessed by the Mini-Mental State Examination) or motor function were observed. The HARMONY study demonstrated a robust decrease in hallucinations and delusions and significant maintenance of efficacy with pimavanserin treatment in DRP.

Study Sponsored By: ACADIA Pharmaceuticals Inc.

Background: There is published evidence of the benefits and limitations, including potential harm, of psychotropic medication and benefits of non-pharmacological interventions for the management of challenging behaviours associated with dementia (BPSD).

Objectives: To examine the usage of such interventions in the management of BPSD within three National Health Service (NHS) ‘specialist’ dementia inpatient wards (56 beds) in a Scottish health region (Fife, population 370,000) and to identify targets for service improvements.

Methods: Patient demographic data, mental and physical health diagnoses, current and recent (within 3 months) psychotropic prescriptions, multidisciplinary team input, and evidence of individualised non-pharmacological interventions for BPSD were collected in February 2020 from patient notes, care plans and medication charts.

Results: 42 older patients (mean age 80 years, range 59-99) with dementia had spent on average 18.7 months within hospital, some categorised as ‘delayed discharges’ awaiting care home placements All lacked capacity to consent to their general care and medical treatments, most having multiple (average 5) medical co-morbidities. 36% were detained in hospital under Mental Health legislation, 29% prescribed medications so authorised, and 40% had medications administered covertly. 76% were prescribed an antipsychotic (Risperidone in 24%), 40% a cognitive enhancer (Memantine and/or a cholinesterase inhibitor), 48% an antidepressant (Trazodone in 19%), 26% a regular benzodiazepine. There was limited regular multi-professional team working in the wards (under 18% had any non-nursing input within the previous 3 months). Of non-pharmacological therapeutic interventions, 26% were receiving multisensory inputs, 19% soft toy, 12% massage, 7% music playlist and 7% cognitive stimulation therapy.

Conclusions: For this population with BPSD there were high rates of off -licence drug prescribing with limited investment in evidence-based non-pharmacological therapeutic alternatives. During ongoing review of staffing on these wards, it would appear appropriate to examine the expectation that wards serve multiple functions, such as transitional care and specialist continuing care. We suggest reviews contextualise prescribing within an increased availability of multi-disciplinary therapeutic interventions, to ensure this patient population is cared for in an evidence-based therapeutic environment. The Scottish Government’s publication3 (2018) “Transforming Specialist Dementia Hospital Care” should help raise the profile of this “overlooked” inpatient population.

3https://www.gov.scot/publications/transforming-specialist-dementia-hospital-care/

Background: Agitation is common in nursing home residents with dementia and is associated with high burden for the residents, their relatives and their caregivers. These consequences increase if symptoms of agitation are severe. Although it is assumed that agitation and quality of life are related, knowledge about severe agitation and its relation to single dimensions of quality of life is limited.

Objective: To examine the relationship between the severity of agitation and social isolation as a dimension of quality of life in people with dementia living in German nursing homes.

Methods: An explorative secondary data analysis of data from an observational study with 1947 residents from 66 German nursing homes was conducted. Agitation was defined as a construct of the items agitation/aggression, irritability and disinhibition of the Neuropsychiatric-Inventory Questionnaire (NPI-Q). Social isolation, as one of the dimensions of quality of life, was measured with a subscale of the short version of the QUALIDEM-instrument. First, a matching procedure was carried out to choose two groups with similar baseline characteristics, one with residents with severe agitation and one with residents with mild or no agitation. Second, a linear regression model and Mann-Whitney U tests were calculated to determine differences in the dimension of social isolation and its single items.

Results: A significant relationship was found between the severity of agitation and the dimension of social isolation (-1.92 (CI 95%: -2.41, -1.43)). Besides the finding in the total score of the dimension of social isolation, significant differences were found in all three items defining this dimension (calls out; openly rejects contact with others; is rejected by other residents). In particular, the item ‘is rejected by other residents’ was often rated as applicable for people with dementia with severe agitation.

Conclusion: Severe agitation is associated with lower values of quality of life in the dimension of social isolation and its defining items. In daily practice and in research, more attention should be paid to severe agitation. Furthermore, interventions that aim to influence both the severity of agitation and the quality of life should have a stronger focus on causes of social isolation.

In Hong Kong, people aged 65 years or more was approximately 17.7% of the total population which is identified as “super-aged” city. The prevalence of dementia in Hong Kong aged 70 years or older had risen from 6.1% to 9.3% between 1998 and 2008. However, only 11% of people with dementia are diagnosed and receive medical follow-up. Although people live longer than they once did, their increased longevity can be a mixed blessing, both for themselves and for their societies. How people perceive dementia and interpret people with dementia will be one of the key elements to develop the 21st century’s dementia care culture in the Chinese society.

A qualitative research in understanding how people with dementia perceive themselves always requires interpreting how others in their daily lives perceive them was conducted. Twenty in-depth interviews and two focus groups between people with dementia and the care staff in the residential care homes in Hong Kong were done. Indeed, if someone in your daily life perceives you differently from how you perceive yourself, then how do you make sense of the discrepancy? People with dementia tend to struggle with understanding not only situations occurring around them but also who they are, especially when others’ reactions to them are unexpected.

Interpretivism and thematic analysis was applied whereas the difference between real and perceived selves was found. The findings included (1) Doubt About One’s Trustworthiness; (2) Doubt About One’s Value; (3) Doubt About One’s Capability. From their perspective, residents with dementia were trustworthy, but the care staff ignored their requests and prerogatives nonetheless. They also interpreted that they were valuable, but the staff overlooked their needs and did not show them any respect, either. Beyond that, they thought that they were capable, but the staff did not recognise their abilities and disregarded their input in decision-making. Puzzled about whether they should accept or reject the staff’s responses in interpreting who they were, the residents with dementia experienced heightened confusion about their circumstances. This research become one of the directions to explore the implementation of person-centred care in the Hong Kong’s residential care homes.

INTRODUCTION: Primary care visits of persons with dementia involve different types of communication, bringing together the patient, the family carer and the general practitioner (GP). A particular challenge is the necessary involvement of a third person (the carer) in patient-doctor encounters (or the patient in carer-doctor encounters, as dementia advances). These triad dynamics should be better understood, as health outcomes are expected to result from or be mediated by them.

OBJECTIVE: Our aim is to explore triadic dynamics in Portuguese primary care consultations with persons with dementia, their family carers and GPs.

METHODS: This is the first part of an ongoing project (Dementia in Primary Care: the Patient, the Carer and the Doctor in the Medical Encounter - Bayer Investigation Grant | NOVAsaúde Ageing 2018). Consultations with persons with dementia, their carers and GPs (purposive sampling) are audio-recorded, transcribed verbatim and thematically analysed. We report the analysis of interactions of the first six consultations, using NVIVO® software.

RESULTS: The most frequent type of interaction was between GPs and carers, followed by interactions involving the whole triad. The patients who had more recent relationships with their GPs tended to participate less, irrespective of the stage of dementia. Carers were the ones most often initiating triadic interactions, and GPs the ones most often terminating them by directly addressing the patients. Doctor-carers interactions were very sparse in some consultations.

DISCUSSION AND CONCLUSION: These preliminary findings suggest that doctor-patient interactions may be limited in a number of GPs’ consultations, seemingly compromising patient-centred approaches. Nevertheless, even when GPs were involved in triadic interactions they often tried to address the patient directly. We are looking forward to complete this part of the project: to our knowledge, there is practically no evidence from live-recorded primary care consultations about these triadic dynamics.

Background & Aims: We aimed to determine neural correlates of olfactory detection and identification and analyze associations between cognitive function and olfactory identification or detection in very mild amnestic patients.

Methods: We recruited 70 patients with chief complaints of memory impairment diagnosed as amnestic mild cognitive impairment (MCI) or Alzheimer’s disease (AD) with a clinical dementia rating of 0.5. Olfactory detection and identification were assessed using T&T olfactometry. A voxel-wise correlation analysis of gray matter volume and olfactometry scores was performed. We also analyzed correlations between neuropsychological results and olfactometry scores.

Results: A significant negative correlation was observed between detection scores and nucleus accumbens and left parahippocampal gyrus volumes and between identification scores and orbitofrontal, right frontal, and right anterior temporal cortex volumes (p<0.001). No significant correlation existed between detection and cognitive assessment scores. Identification score was significantly correlated with the Alzheimer’s Disease Assessment Scale-Cognitive Part word recall score (r=0.305, p=0.01).

Conclusions: Olfactory detection and identification dysfunction were attributable to impairments in different regions in MCI and very early AD; the former was attributed to the olfactory circuit, while the latter to neocortices. The dysfunction of identification of olfactory information was associated with episodic memory in those patients.

Objective: Compare burden of disease among patients with dementia-related psychosis (DRP), dementia without psychosis (dementia only), and dementia-related agitation/aggression (DAA) in long-term care (LTC) facilities.

Background: Patients with dementia often experience neuropsychiatric symptoms (NPS), including psychosis and agitation/aggression. Real-world data on the comorbidity profile of DRP and DAA patients are limited.

Design/Methods: Dementia patients were identified from a US LTC database based on ?2 dementia diagnosis codes or 1 dementia diagnosis code and antidementia therapy prescription during 1 Jan 2013 to 30 May 2017. Patients were categorized into DRP (?2 psychosis or 1 psychosis diagnosis code and prescription of antipsychotic therapy and no history of agitation/aggression diagnosis), dementia only (no psychosis or agitation/aggression diagnosis and no history of antipsychotic therapy [dementia only]), and DAA (?2 diagnosis codes of agitation/aggression and no history of psychosis diagnosis or antipsychotic therapy) groups (index date). Comorbidities and concomitant therapies were defined during 12 months prior to index date.

Results: There were 26,002 dementia residents: DRP (n=11,921; 46%); dementia only (n=11,432; 44%); DAA (n=2649; 10%). DRP patients were younger (mean age 80.8 years) than dementia only (84.3 years) or DAA (83.8 years). DRP patients were sicker overall versus dementia only: anemia (32% vs 29%); anxiety (55% vs 33%); bladder disorders (19% vs 13%); depression (75% vs 58%); hypertension (43% vs 33%); diabetes (43% vs 38%); insomnia disorders (32% vs 19%); (all P<0.05). More DAA patients had anxiety (43%), depression (66%), hypertension (43%), and insomnia disorders (26%) than dementia only (all P<0.05). Most DRP patients (94.3%) received off-label treatment for DRP; approximately one third (31.6%) of DAA patients received off-label treatment for DRP.

Conclusions: This study, the first of its type to use a US LTC database, demonstrated a significant comorbidity burden associated with DRP or DAA compared with dementia only, which should be considered when using off-label treatments. These data highlight the need for safe and effective treatments for dementia NPS.

Study Sponsored By: ACADIA Pharmaceuticals Inc.

There is limited understanding of which factors most influence take-up of DRR behaviour in the general population. This evidence gap may limit the effectiveness of DRR implementation and, hence, impede translation of increasing evidence for DRR1 into real-world public health benefits.

Reviews of quantitative studies have identified poor knowledge and persistence of myths about ageing2,3 as important. However, these findings are limited by the scope of included questionnaires.

Qualitative literature reporting the perspectives of the general public offers an opportunity to increase this understanding. Qualitative studies can examine poorly understood phenomena in greater depth and with fewer a priori assumptions. Qualitative evidence synthesis (QES) is increasingly recognised as valuable, particularly in relation to complex interventions like DRR.

We will present a QES regarding the perspectives of dementia- free members of the general public towards DRR. Searches indicate that no QES for this topic currently exists.

Systematic searches of Medline, PsycINFO, Embase and CINAHL for studies published since 1995 that have used qualitative methods to explore DRR perspectives in the general public were undertaken, supplemented by hand searches of included studies’ reference lists. Following independent screening by two reviewers, 41 publications based on 37 individual studies meeting inclusion criteria have been identified.

Data will be analysed using thematic synthesis, as outlined by Thomas and Harden (2008)4 and recommended for QES regarding complex health interventions5. ‘Line-by-line’ inductive coding and development of descriptive themes across studies will produce a summary of the perspectives of the general public for DRR. A conceptual framework explaining the relationships between key themes and considering the implications for implementation will be proposed.

The Critical Appraisal Skills Programme (CASP) tool will be used to appraise included studies. Rather than imposing an arbitrary quality cut-off point for inclusion, sensitivity analyses will be used to examine the influence of lower quality studies on review findings. Finally, the Confidence in the Evidence from Qualitative Reviews (CERQual) approach will facilitate assessment of confidence in review findings to aid future use. Data extraction is ongoing.

Findings from this synthesis will support better targeted quantitative examination of DRR implementation determinants and more strategic intervention design.

1. 1. World Health Organisation. Risk reduction of cognitive decline and dementia: WHO guidelines. World Health Organisation. 2019. Geneva. Licence CC BY-NC-SA 3.0 IGO

2. 2. Cahill, S., Pierce, M., Werner, P., Darley, A., Bobersky, A. A systematic review of the public’s knowledge and understanding of Alzheimer’s disease and dementia. Alz Dis Assoc Disord. 2015; 29:255-275

3. 3. Cations, M., Radisic, G., Crotty, M., Laver, K.E. What does the general public understand about prevention and treatment of dementia? A systematic review of population-based surveys. PLoS One. 2018, 13(4):e0196085

4. 4. Thomas, J. and Harden, A. (2008). Methods for the thematic synthesis of qualitative research in systematic reviews, BMC Medical Research Methodology. 2008 July; 8:45. doi 10.1186/1471-2288-8-45

5. 5. Noyes, J., Booth, A., Cargo, M., et al. (2018). Cochrane Qualitative and Implementation Methods Group guidance series – paper 1: introduction. J of Clin Epidemiol. 2018; 97:35-38

Among the preventable complications of diseases that require urgent effective health literacy programs in sub-Saharan Africa, crosstalk between diabetes and dementia stands out for women's health. Type 2 diabetes mellitus (DM2) in midlife is a recognised risk factor for dementia. This crosstalk is more significant in persons of African ancestry. Globally, the prevalence of DM will increase dramatically in the next few years with 75% of cases living in low-to-middle-income countries. Some major risk factors for DM2 accelerates the development of dementia in Africa-Americans, thus leading to higher prevalence of dementia compared to Caucasians. It is known that 58% of the global 46.8 million dementia subjects lives in economically developing countries. This proportion may reach 63% and 68% in 12 and 32 years' time, respectively. Females are 1.5 times likely to develop dementia, but sub-Saharan Africa women have a disproportionately two-to-eight fold increased dementia risk. In the eye of this storm is Nigeria which is home to the highest number of diabetics in Africa. Diabetes prevalence in the country is rising parallel to increased incidence of obesity, hypertension and rising population age. The socioeconomic impact of increasing prevalence of DM2 and dementia will be unsustainable for Nigeria healthcare system, given the experiences in developed economies. This study analyses the current situation of women's health in Nigeria, and explore future policy directions. The complex interplay of factors involved in the DM2-dementia crosstalk in Nigerian women include those due to biological processes (metabolic syndrome, vascular damage, inflammation, oxidative stress, insulin resistance and anaemia), nutritional habits and sedentary lifestyles. Other factors that predisposes Nigerian diabetic women to dementia are, restricted resources, lack of visibility and poor health management. They add up to increase the burden of disease in the Nigerian woman, irrespective of age. We advise urgent implementation of heath policies and actions that will increase ratio of mental health professionals / number of patients, especially in rural areas and the establishment of proactive primary healthcare centres. Importantly, interventions targeting adolescents and adult women, and others specific to mother- child interactions, are strongly needed in Nigeria and the sub-region for mitigating dementia in women.

Alzheimer’s disease (AD) is associated with brain oxidative stress, inflammation, and cerebrovascular disease. Structural and functional abnormalities in cerebral microvasculature have been described in both patients and animals models. New tools and biomarkers for the detection of the disease are still emerging, such as Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for non-invasive measurements of cerebral blood blow (CBF) whose alteration may be involved in AD-pathogenesis. Nevertheless, more studies in the field are needed since both hypoperfusion and hyperperfusion in different brain areas are reported and can be involved in different brain functions. Recently, we reported in our colony of 3xTg-AD mice modeling Alzheimer’s disease a higher number of β-amyloid plaques in the hippocampus and entorhinal cortex in middle-aged females and extensive regions of hypoxia which were not seen in males. In the present study, we evaluated CBF in five different brain regions (hippocampus, cortex, striatum, caudate putamen and amygdala) in older male and female surviving until very advanced-stages of disease and as compared with age-matched counterparts with normal aging. AD-phenotype was evaluated by a comprehensive screening of three main functional impairments: physical (frailty), BPSD-like and cognitive deficits. CBF was measured using MRI-ASL and meaningful correlations between AD-phenotype and CBF were performed to better understand the relation between the level of perfusion and frailty, the BPSD-like behaviors and cognitive impairments. The results indicated sex- and brain region-associated changes in CBF. Among all, 3xTg-AD female mice survivors had increased CBF in cortex and hippocampus as compared with their wildtype counterparts. Here, we also report, for the first time, asymmetry between left -right hemispheres in the female’s cortex, in the hippocampus of control males and 3xTg-AD females, as well as in the striatum of control females. Cortex was the area that better correlated with behavior, with asymmetry being associated with worse memory performance. Moreover, hemisphere CBF asymmetry in limbic system was related with copying-with-stress strategies and associated locomotor activity in anxiety tests. The present study suggests a potential compensatory hemodynamic mechanism in end-of-life dementia which is sex- and brain region dependent and can be target for pharmacological and non-pharmacological interventions.