Beyond mild cognitive impairment: vascular cognitive impairment, no dementia (VCIND)

Identifying the causes of dementia is important in the search for effective preventative and treatment strategies. The concept of mild cognitive impairment (MCI), as prodromal dementia, has been useful but remains controversial since in population-based studies it appears to be a limited predictor of progression to dementia. Recognising the relative contribution of neurodegenerative and vascular causes, as well as their interrelationship, may enhance predictive accuracy. The concept of vascular cognitive impairment (VCI) has been introduced to describe the spectrum of cognitive change related to vascular causes from early cognitive decline to dementia. A recent review of this concept highlighted the need for diagnostic criteria that encompass the full range of the VCI construct. However, very little is known regarding the mildest stage of VCI, generally termed 'vascular cognitive impairment, no dementia' (VCIND). Whether mild cognitive change in the context of neurodegenerative pathologies is distinct from that in the context of cerebrovascular diseases is not known. This is key to the definition of VCIND and whether it is possible to identify this state. Distinguishing between vascular (that is, VCIND) and non-vascular (that is, MCI) cognitive disorders and determining how well each might predict dementia may not be possible due to the overlap in pathologies observed in the older population. Here, we review the concept of VCIND in an effort to identify recent developments and areas of controversy in nosology and the application of VCIND for screening individuals at increased risk of dementia secondary to vascular disease and its risk factors

Two-decade change in prevalence of cognitive impairment in the UK.

Identification of individuals at high risk of dementia has usually focused attention on the clinical concept of mild cognitive impairment (MCI), which captures an intermediate state between normal cognitive ageing and dementia. In many countries age specific risk of dementia has declined, but whether this is also the case for subclinical cognitive impairment is unknown. This has important implications for prevention, planning and policy. Here we describe subclinical cognitive impairment and mild dementia prevalence changes, in the UK, over 2 decades. The Cognitive Function and Ageing Studies have examined the full spectrum of cognition, from normal to dementia, in representative populations of people aged ≥ 65 years in the UK over the last 2 decades 7635 participants were interviewed in CFAS I in Cambridgeshire, Newcastle, and Nottingham in 1991, with 1457 being diagnostically assessed. In the same geographical areas, the CFAS II investigators interviewed 7796 individuals in 2011. Using established criteria, the population was categorised into seven groups: no cognitive impairment, Mild cognitive Impairment (defined using consensus criteria), other cognitive impairment no dementia without functional impairment, OCIND with functional impairment, cognitive impairment (MMSE < 24 and no functional impairment), mild dementia (MMSE < 24 with functional impairment, not captured by CFAS dementia criteria), and CFAS dementia criteria. Multinomial logistic regression, adjusted for age and sex, was used to estimate the prevalence of impairment in both studies. Results were standardized to the age-sex specific UK and global population. There is a clear increase in the prevalence of other cognitive Impairment no Dementia (without functional impairment), with the purer MCI remaining stable. In the UK, mild dementia is estimated to fall from 520,704 cases (5.7%, 95% CI 3.8, 8.1) in 1991 to 315,142 (3.0%, 95% CI 2.4, 3.8) in 2011, cognitive impairment, has fallen from 1,225,984 (13.5%, 95% CI 10.1, 17.5) to 654,436 (6.3%, 95% CI 5.4, 7.3) cases. Using additional categories which reflect the continuum of cognitive decline and impairment in populations we see that the mildest dementia declines, but that there is stability in estimates of those who meet MCI criteria. Increases were found in the Other Cognitive Impairment no Dementia group. The decline observed in severe impairment thus seems to have resulted in larger proportions of the population in milder forms, seen alongside physical illnesses

Health-related quality of life in the Cambridge City over-75s Cohort (CC75C): development of a dementia-specific scale and descriptive analyses.

BACKGROUND: The assessment of Health Related Quality of Life (HRQL) is important in people with dementia as it could influence their care and support plan. Many studies on dementia do not specifically set out to measure dementia-specific HRQL but do include related items. The aim of this study is to explore the distribution of HRQL by functional and socio-demographic variables in a population-based setting. METHODS: Domains of DEMQOL's conceptual framework were mapped in the Cambridge City over 75's Cohort (CC75C) Study. HRQL was estimated in 110 participants aged 80+ years with a confirmed diagnosis of dementia with mild/moderate severity. Acceptability (missing values and normality of the total score), internal consistency (Cronbach's alpha), convergent, discriminant and known group differences validity (Spearman correlations, Wilcoxon Mann-Whitney and Kruskal-Wallis tests) were assessed. The distribution of HRQL by socio-demographic and functional descriptors was explored. RESULTS: The HRQL score ranged from 0 to 16 and showed an internal consistency Alpha of 0.74. Validity of the instrument was found to be acceptable. Men had higher HRQL than women. Marital status had a greater effect on HRQL for men than it did for women. The HRQL of those with good self-reported health was higher than those with fair/poor self-reported health. HRQL was not associated with dementia severity. CONCLUSIONS: To our knowledge this is the first study to examine the distribution of dementia-specific HRQL in a population sample of the very old. We have mapped an existing conceptual framework of dementia specific HRQL onto an existing study and demonstrated the feasibility of this approach. Findings in this study suggest that whereas there is big emphasis in dementia severity, characteristics such as gender should be taken into account when assessing and implementing programmes to improve HRQL

Effects of Subjective Memory Complaints (SMCs) and Social Capital on Self-Rated Health (SRH) in a Semirural Malaysian Population

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420Subjective memory complaints (SMCs) and social capital were known to be related to self-rated health (SRH). Despite this, no studies have examined the potential interaction of SMC and social capital on SRH. Using data from a cross-sectional health survey of men and women aged 56 years and above (n = 6,421), we examined how SMCs and social capital explained SRH in a population of community-dwelling older adults in a semirural area in Malaysia. We also evaluated whether SRH’s relationship with SMCs is moderated by social capital. The association of SMC and social capital with poor SRH was investigated using multivariable logistic regression. Social capital (OR = 0.86, 95% CI = 0.82–0.89), mild SMC (OR = 1.70, 95% CI = 1.50–1.94), and moderate SMC (OR = 1.90, 95% CI = 1.63–2.20) were found to be associated with poor SRH after adjustment for sociodemographic factors and depression in the initial regression model. SMC was found to have partial interaction effects with social capital which was included in the subsequent regression model. Unlike individuals with no SMC and mild SMC, those who reported moderate SMC did not show decreasing probabilities of poor SRH despite increasing levels of social capital. Nevertheless, this analysis suggests that social capital and SMC are independent predictors of poor SRH. Further research needs to be targeted at improving the understanding on how social capital and SMC moderate and interact with the perception of health in older adults.https://doi.org/10.1155/2019/915180

Protocol of a feasibility study for cognitive assessment of an ageing cohort within the Southeast Asia Community Observatory (SEACO), Malaysia

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420Introduction There is a growing proportion of population aged 65 years and older in low-income and middle-income countries. In Malaysia, this proportion is predicted to increase from 5.1% in 2010 to more than 15.4% by 2050. Cognitive ageing and dementia are global health priorities. However, risk factors and disease associations in a multiethnic, middle-income country like Malaysia may not be consistent with those reported in other world regions. Knowing the burden of cognitive impairment and its risk factors in Malaysia is necessary for the development of management strategies and would provide valuable information for other transitional economies. Methods and analysis This is a community-based feasibility study focused on the assessment of cognition, embedded in the longitudinal study of health and demographic surveillance site of the South East Asia Community Observatory (SEACO), in Malaysia. In total, 200 adults aged ≥50 years are selected for an in-depth health and cognitive assessment including the Mini Mental State Examination, the Montreal Cognitive Assessment, blood pressure, anthropometry, gait speed, hand grip strength, Depression Anxiety Stress Score and dried blood spots. Discussion and conclusions The results will inform the feasibility, response rates and operational challenges for establishing an ageing study focused on cognitive function in similar middle-income country settings. Knowing the burden of cognitive impairment and dementia and risk factors for disease will inform local health priorities and management, and place these within the context of increasing life expectancy. Ethics and dissemination The study protocol is approved by the Monash University Human Research Ethics Committee. Informed consent is obtained from all the participants. The project's analysed data and findings will be made available through publications and conference presentations and a data sharing archive. Reports on key findings will be made available as community briefs on the SEACO websitehttp://dx.doi.org/10.1136/bmjopen-2016-0136357pubpub

Recurrent delirium over 12 months predicts dementia: results of the Delirium and Cognitive Impact in Dementia (DECIDE) study.

BACKGROUND: Delirium is common, distressing and associated with poor outcomes. Previous studies investigating the impact of delirium on cognitive outcomes have been limited by incomplete ascertainment of baseline cognition or lack of prospective delirium assessments. This study quantified the association between delirium and cognitive function over time by prospectively ascertaining delirium in a cohort aged ≥ 65 years in whom baseline cognition had previously been established. METHODS: For 12 months, we assessed participants from the Cognitive Function and Ageing Study II-Newcastle for delirium daily during hospital admissions. At 1-year, we assessed cognitive decline and dementia in those with and without delirium. We evaluated the effect of delirium (including its duration and number of episodes) on cognitive function over time, independently of baseline cognition and illness severity. RESULTS: Eighty two of 205 participants recruited developed delirium in hospital (40%). One-year outcome data were available for 173 participants: 18 had a new dementia diagnosis, 38 had died. Delirium was associated with cognitive decline (-1.8 Mini-Mental State Examination points [95% CI -3.5 to -0.2]) and an increased risk of new dementia diagnosis at follow up (OR 8.8 [95% CI 1.9-41.4]). More than one episode and more days with delirium (>5 days) were associated with worse cognitive outcomes. CONCLUSIONS: Delirium increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition, with more episodes associated with worse cognitive outcomes. Given that delirium has been shown to be preventable in some cases, we propose that delirium is a potentially modifiable risk factor for dementia

A comparison of health expectancies over two decades in England: results of the Cognitive Function and Ageing Study I and II.

BACKGROUND: Whether rises in life expectancy are increases in good-quality years is of profound importance worldwide, with population ageing. We investigate how various health expectancies have changed in England between 1991 and 2011, with identical study design and methods in each decade. METHODS: Baseline data from the Cognitive Function and Ageing Studies in populations aged 65 years or older in three geographically defined centres in England (Cambridgeshire, Newcastle, and Nottingham) provided prevalence estimates for three health measures: self-perceived health (defined as excellent-good, fair, or poor); cognitive impairment (defined as moderate-severe, mild, or none, as assessed by Mini-Mental State Examination score); and disability in activities of daily living (defined as none, mild, or moderate-severe). Health expectancies for the three regions combined were calculated by the Sullivan method, which applies the age-specific and sex-specific prevalence of the health measure to a standard life table for the same period. FINDINGS: Between 1991 and 2011, gains in life expectancy at age 65 years (4·5 years for men and 3·6 years for women) were accompanied by equivalent gains in years free of any cognitive impairment (4·2 years [95% CI 4·2-4·3] for men and 4·4 years [4·3-4·5] for women) and decreased years with mild or moderate-severe cognitive impairment. Gains were also identified in years in excellent or good self-perceived health (3·8 years [95% CI 3·5-4·1] for men and 3·1 years [2·7-3·4] for women). Gains in disability-free years were much smaller than those in excellent-good self-perceived health or those free from cognitive impairment, especially for women (0·5 years [0·2-0·9] compared with 2·6 years [2·3-2·9] for men), mostly because of increased mild disability. INTERPRETATION: During the past two decades in England, we report an absolute compression (ie, reduction) of cognitive impairment, a relative compression of self-perceived health (ie, proportion of life spent healthy is increasing), and dynamic equilibrium of disability (ie, less severe disability is increasing but more severe disability is not). Reasons for these patterns are unknown but might include increasing obesity during previous decades. Our findings have wide-ranging implications for health services and for extension of working life. FUNDING: UK Medical Research Council

Apolipoprotein ɛ4 is associated with increased risk of fall- and fracture-related hospitalisation: the Perth Longitudinal Study of Ageing Women

Apolipoprotein ɛ4 (APOE ɛ4) may be a genetic risk factor for reduced bone mineral density (BMD) and muscle function, which could have implications for fall and fracture risk. We examined the association between APOE ɛ4 status and long-term fall- and fracture-related hospitalisation risk in older women. 1276 community-dwelling women from the Perth Longitudinal Study of Ageing Women (mean age ± SD = 75.2 ± 2.7 years) were included. At baseline, women underwent APOE genotyping and detailed phenotyping for covariates including prevalent falls and fractures, as well as health and lifestyle factors. The association between APOE ɛ4 with fall-, any fracture-, and hip fracture-related hospitalisations, obtained over 14.5 years from linked health records, were examined using multivariable-adjusted Cox-proportional hazard models. Over 14.5 years, 507 (39.7%) women experienced a fall-related hospitalisation, 360 (28.2%) women experienced a fracture-related hospitalisation, including 143 (11.2%) attributed to a hip fracture. In multivariable-adjusted models, compared to non-carriers, APOE ɛ4 carriers (n=297, 23.3%) had greater risk for a fall- (HR 1.48 95%CI 1.22-1.81), fracture- (HR 1.28, 95%CI 1.01-1.63) or hip fracture-related hospitalisation (HR 1.83 95%CI 1.29-2.61). The estimates remained similar when specific fall and fracture risk factors (fear of falling, plasma 25-hydroxyvitamin D, grip strength, timed-up-and-go, hip BMD, vitamin K status, prevalent diabetes, HbA1c, cholesterol, abbreviated mental test score) were added to the multivariable model. In conclusion, APOE ɛ4 is a potential risk factor for fall- and fracture-related hospitalisation in community-dwelling older women. Screening for APOE ɛ4 could provide clinicians an opportunity to direct higher risk individuals to appropriate intervention strategies

The economic burden of dementia in low- and middle-income countries (LMICs): a systematic review

Introduction More than two-thirds of people with dementia live in low- and middle-income countries (LMICs), resulting in a significant economic burden in these settings. In this systematic review, we consolidate the existing evidence on the cost of dementia in LMICs. Methods Six databases were searched for original research reporting on the costs associated with all-cause dementia or its subtypes in LMICs. The national-level dementia costs inflated to 2019 were expressed as percentages of each country’s gross domestic product (GDP) and summarised as the total mean percentage of GDP. The risk of bias of studies was assessed using the Larg and Moss method. Results We identified 14 095 articles, of which 24 studies met the eligibility criteria. Most studies had a low risk of bias. Of the 138 LMICs, data were available from 122 countries. The total annual absolute per capita cost ranged from US$590.78 for mild dementia to US$25 510.66 for severe dementia. Costs increased with the severity of dementia and the number of comorbidities. The estimated annual total national costs of dementia ranged from US$1.04 million in Vanuatu to US$195 billion in China. The average total national expenditure on dementia estimated as a proportion of GDP in LMICs was 0.45%. Indirect costs, on average, accounted for 58% of the total cost of dementia, while direct costs contributed 42%. Lack of nationally representative samples, variation in cost components, and quantification of indirect cost were the major methodological challenges identified in the existing studies. Conclusion The estimated costs of dementia in LMICs are lower than in high-income countries. Indirect costs contribute the most to the LMIC cost. Early detection of dementia and management of comorbidities is essential for reducing costs. The current costs are likely to be an underestimation due to limited dementia costing studies conducted in LMICs, especially in countries defined as low- income. PROSPERO registration number The protocol was registered in the International Prospective Register of Systematic Reviews database with registration number CRD42020191321.http://dx.doi.org/10.1136/bmjgh-2021-0074097pubpub

Link Between Dietary Sodium Intake, Cognitive Function, and Dementia Risk in Middle-Aged and Older Adults: A Systematic Review

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420Background: A key focus for dementia risk-reduction is the prevention of socio-demographic, lifestyle, and nutritional risk factors. High sodium intake is associated with hypertension and cardiovascular disease (both are linked to dementia), generating numerous recommendations for salt reduction to improve cardiovascular health. Objective: This systematic review aimed to assess, in middle- and older-aged people, the relationship between dietary sodium intake and cognitive outcomes including cognitive function, risk of cognitive decline, or dementia. Methods: Six databases (PubMed, EMBASE, CINAHL, Psych info, Web of Science, and Cochrane Library) were searched from inception to 1 March 2020. Data extraction included information on study design, population characteristics, sodium reduction strategy (trials) or assessment of dietary sodium intake (observational studies), measurement of cognitive function or dementia, and summary of main results. Risk-of-bias assessments were performed using the National Heart, Lung, and Blood Institute (NHLBI) assessment tool. Results: Fifteen studies met the inclusion criteria including one clinical trial, six cohorts, and eight cross-sectional studies. Studies reported mixed associations between sodium levels and cognition. Results from the only clinical trial showed that a lower sodium intake was associated with improved cognition over six months. In analysis restricted to only high-quality studies, three out of four studies found that higher sodium intake was associated with impaired cognitive function. Conclusion: There is some evidence that high salt intake is associated with poor cognition. However, findings are mixed, likely due to poor methodological quality, and heterogeneous dietary, analytical, and cognitive assessment methods and design of the studies. Reduced sodium intake may be a potential target for intervention. High quality prospective studies and clinical trials are needed.https://doi.org/10.3233/JAD-19133976pubpub