Type 1 diabetes, cognitive ability and incidence of cardiovascular disease and death over 60 years of follow-up time in men.

AIMS: There are few cohorts of type 1 diabetes that follow individuals over more than half a century in terms of health outcomes. The aim of this study was to examine associations between type 1 diabetes, diagnosed before age 18, and long-term morbidity and mortality, and to investigate whether cognitive ability plays a role in long-term morbidity and mortality risk. METHODS: In a Swedish cohort, 120 men with type 1 diabetes and 469 without type 1 diabetes were followed between 18 and 77 years of age as regards morbidity and mortality outcomes, and impact of cognitive ability at military conscription for the outcomes. In Cox regression analyses and Kaplan-Meier analyses with log-rank tests, associations between diabetes and cognitive ability respectively, and outcomes (mortality, cardiovascular morbidity and diabetes complications) were investigated. RESULTS: Men with type 1 diabetes suffered from dramatically higher mortality (HR 4.62, 95% CI: 3.56-5.60), cardiovascular mortality (HR 5.60, 95% CI: 3.27-9.57), and cardiovascular events (HR 3.97, 95% CI: 2.79-5.64) compared to men without diabetes. Higher cognitive ability at military conscription was associated with lower mortality in men without diabetes, but was not associated with any outcome in men with diabetes. CONCLUSIONS: In this historical cohort study with 60 years of follow-up time and a less effective treatment of diabetes than today, mortality rates and cardiovascular outcomes were high for men with type 1 diabetes. Morbidity or mortality did not differ between those that had low to normal or high cognitive ability among men with type 1 diabetes.

Elder abuse and life-course victimization in hospitalized older adults in Sweden: prevalence and associations with mental ill-health.

BACKGROUND: The prevalence of elder abuse has only rarely been investigated in Sweden and never in a hospital setting. Therefore, the aims of this study were to: 1) Estimate the prevalence of elder abuse and life-course victimization among hospitalized older adults in Sweden, 2) Explore factors associated with elder abuse in the same sample, and 3) Explore the associations between life-course victimization and mental ill-health. METHODS: The study was conducted at a university hospital in Sweden. Adults over the age of 65 years admitted to a medical or geriatric acute care ward during spring 2018 were consecutively recruited. The participant rate was 44% (n = 135/306). Participants were assessed via a face-to-face interview about their experiences of elder abuse and abuse earlier in life. Mental ill-health was measured using a self-administered depression assessment (Patient Health Questionnaire-9), along with information about medications and diagnoses retrieved from medical records. RESULTS: Altogether, 40.7% (n = 55) of the participants reported some form of abusive experience during their life course. The prevalence of elder abuse was 17.8% (n = 24), and 58% (n = 14) of elder abuse victims also reported victimization earlier in life. Being abused before the age of 65 was the only background factor associated with elder abuse (OR = 5.4; 95% CI 1.9-15.7). Reporting abusive experiences both before and after the age of 65 was associated with current anti-depressant medication (OR = 6.6; 95% CI 1.1-39.2), a PHQ-9 result of 10 or more (OR = 10.4; 95% CI 2.1-51.0), and nine or more symptom diagnoses (OR = 4.0, 95% CI 1.0-16.1). Being abused only before or after the age of 65 was not significantly associated with any mental ill-health outcome measure. CONCLUSIONS: Elder abuse and victimization earlier in life are highly prevalent among hospitalized older patients, and our findings underline the importance of a life-course perspective both in research on elder abuse and in clinical practice. Identifying and caring for older adults who have been subjected to abuse should be a priority in health care.

Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia.

OBJECTIVE: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies. METHODS: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), ß-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009-2015). RESULTS: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03-1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10-1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07-3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87-1.90] for Aß42 and 1.35 [95% CI = 0.86-2.13] for Aß42 /p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies. INTERPRETATION: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2020;87:52-62.

Mortality in patients with behavioural and psychological symptoms of dementia: a registry-based study.

OBJECTIVES: Behavioural and psychological symptoms of dementia (BPSD) are common in patients with dementia. In the elderly population, comorbidities frequently coexist with dementia and mortality in dementia is high. The aim of this study was to investigate the impact of BPSD on mortality in severe dementia. METHODS: This study of 11,448 individuals was based on linked information from the Swedish BPSD registry, the National Patient Register and the Cause of Death register. BPSD was assessed with the Neuropsychiatric Inventory (NPI). Cox proportional hazards regressions were performed for survival analysis. To study different degrees of BPSD, data was categorized into groups: no (NPI, 0 points), mild (NPI, 1-3 points on ≥1 item), moderate (NPI, 4-8 points on ≥1 item) and severe (NPI, 9-12 points on ≥1 item) BPSD based on the highest score on any of the BPSD assessed (NPI items). RESULTS: The presence of moderate or severe BPSD was associated with a stepwise increased risk of mortality (hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.08-1.60 and HR 1.74; 95% CI 1.44-2.12, respectively) compared with individuals with no BPSD. In addition, there was an association between total NPI score and mortality (HR 1.01; 95% CI 1.007-1.010). The results remained significant after multivariable adjustment for age, sex, dementia diagnosis, medication, previous myocardial infarction, hip fracture and stroke. CONCLUSIONS: The results show a stepwise increase in mortality risk with increased BPSD, highlighting the importance of adequate management of BPSD to reduce mortality in dementia.

Facilitators and barriers associated with the implementation of a Swedish psychosocial dementia care programme in Japan: a secondary analysis of qualitative and quantitative data.

BACKGROUND: A psychosocial dementia care programme for challenging behaviour (DEMBASE® ) was developed in collaboration with a Swedish BPSD-registry team for in-home care services use in Japan. The programme consisted of a web-based tool for the continued assessment of challenging behaviours and interdisciplinary discussion meetings. Effectiveness of the adapted programme was verified through a cluster-randomised controlled trial. The Tokyo Metropolitan Government provided municipal funding to introduce the programme into daily practice beginning in April 2018. OBJECTIVES: To investigate both facilitators and barriers associated with programme implementation. DESIGN: A secondary analysis of qualitative and quantitative data. SETTINGS: Data were collected in naturalistic long-term care settings from April 2018 to March 2019. PARTICIPANTS: A total of 138 professionals and 157 people with dementia participated in the programme. METHODS: Challenging behaviour in persons with dementia was assessed by professionals using a total Neuropsychiatric Inventory score. Data on expected facilitators and barriers were extracted for qualitative analysis from a debriefing meeting between professionals. RESULTS: Of the 157 persons with dementia, 81 (51.6%) received follow-up behavioural evaluations by March 2019. The average level of challenging behaviour was significantly reduced for 81 persons from baseline to their most recent follow-up evaluations. Facilitators included 'programme available for care managers', 'visualised feedback on professionals' work', 'affordable for providers and professionals' and 'media coverage'. Barriers included 'professionals from different organisations', 'unpaid work', 'operation requirement for municipalities' and 'conflict with daily benefit-oriented framework'. CONCLUSIONS: A follow-up evaluation was not fully achieved. Further strategies to address barriers may include the development of a benefit-rewarding scheme for interdisciplinary discussion meetings, an e-learning system capable of substituting training course portions and a cross-municipality training course.

Validation of REAGERA-S: a new self-administered instrument to identify elder abuse and lifetime experiences of abuse in hospitalized older adults.

This study aimed to develop and validate REAGERA-S, a self-administered instrument to identify elder abuse as well as lifetime experiences of abuse in older adults. REAGERA-S consists of nine questions concerning physical, emotional, sexual, financial abuse and neglect. Participants were recruited among patients (≥ 65 years) admitted to acute in-hospital care (n = 179). Exclusion criteria were insufficient physical, cognitive, or language capacity to complete the instrument. A semi-structured interview conducted by a physician was used as a gold standard against which to assess the REAGERA-S. The final version was answered by 95 older adults, of whom 71 were interviewed. Sensitivity for lifetime experiences of abuse was 71.9% and specificity 92.3%. For elder abuse, sensitivity was 87.5% and specificity was 92.3%. REAGERA-S performed well in validation and can be recommended for use in hospitals to identify elder abuse as well as life-time experience of abuse among older adults.

CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics.

OBJECTIVE: To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer's disease-related amyloid ß (Aß) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. METHODS: The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson's disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer's disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPß), Aß species (Aß38, Aß40 and Aß42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1). RESULTS: Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aß40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aß40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers. CONCLUSIONS: The combination of the CSF biomarkers T-tau, Aß40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.

Pre-diabetes and diabetes are independently associated with adverse cognitive test results: a cross-sectional, population-based study.

BACKGROUND: Diabetes is a risk factor for cognitive impairment, but whether there is also a link between pre-diabetes and cognitive dysfunction is not yet fully established. The aim of this observational study was to investigate associations between pre-diabetes/diabetes and cognitive test results, and also between glucose levels measured during the Oral Glucose Tolerance Test (OGTT) and cognitive outcomes. METHODS: During 2007-2012, in all 2994 people (mean age 72 years), residing in Malmö, Sweden, underwent a clinical examination including the OGTT, cardiovascular measurements including carotid-femoral pulse wave velocity (c-f PWV) and two cognitive tests, the Mini Mental State Examination (MMSE), measuring global cognitive function, and A Quick Test of Cognitive Speed (AQT), measuring processing speed and executive functioning. Regression analyses were performed to investigate associations between: (a) categories of normal or impaired glucose metabolism, and (b) OGTT measurements, respectively, as exposure variables and cognitive test results as outcomes. Adjustments were made for demographics, lifestyle factors and cardiovascular risk factors. RESULTS: Participants with pre-diabetes and diabetes scored slightly worse cognitive test results compared to the control group. Results of participants with a long disease duration of diabetes since the baseline examination 13 years earlier were poorer (mean AQT test time 17.8 s slower than controls, p < 0.001). Linear associations were found between fasting and 2-h glucose and cognitive outcomes in the whole population, but also in a sub-analysis including only individuals without diabetes (for 2-h glucose and MMSE results: B = - 2.961, p = 0.005). Associations were stronger for older or less physically active individuals. When adjusting for cardiovascular risk factors, most correlations were non-significant. CONCLUSIONS: Pre-diabetes and diabetes are associated with minor deficits in global cognitive function, processing speed and executive functioning. Long-standing diabetes is associated with bigger deficits. There appears to be a continuous inverse correlation between glucose levels and cognitive test results, also for people without diabetes. Associations are stronger in older and less physically active individuals. Cardiovascular factors are important mediating factors in the pathway between diabetes and cognitive dysfunction.

Psychosocial behaviour management programme for home-dwelling people with dementia: A cluster-randomized controlled trial.

Little is known about the effectiveness of a psychosocial behaviour management programme on home-dwelling people with dementia. We developed a Behaviour Analytics & Support Enhancement (BASE) programme for care managers and professional caregivers of home care services in Japan. We investigated the effects of BASE on challenging behaviour of home-dwelling people with dementia. METHODS: A cluster-randomized controlled trial was conducted with home care providers from 3 different districts in Tokyo. Each provider recruited persons with dementia aged 65 years or older to receive home care in the BASE programme in August 2016. An online monitoring and assessment system was introduced to the intervention group for repeated measures of challenging behaviour with a total score of the Neuropsychiatric Inventory. Care professionals in both the intervention and control groups evaluated challenging behaviour of persons with dementia at baseline (September 2016) and follow-up (February 2017). RESULTS: A majority of persons with dementia had Alzheimer disease (59.3%). One-hundred and forty-one persons with dementia were included in the intervention group and 142 in the control group. Multilevel modelling revealed a significant reduction in challenging behaviour in the intervention group after 6 months (mean score, 18.3 to 11.2) compared with that of the control group (11.6 to 10.8; P < .05). CONCLUSION: The implementation of the BASE programme resulted in a reduction of challenging behaviour of home-dwelling people with dementia. Future research should examine the long-term effects of behaviour management programmes on behaviour, nursing home placement, and hospital admission of home-dwelling people with dementia.

Dementia behaviour management programme at home: impact of a palliative care approach on care managers and professional caregivers of home care services.

OBJECTIVES: Care managers and professional caregivers of home care services are sometimes unaware of the psychosocial approaches to the challenging behaviour of dementia. Therefore, we developed a Behaviour Analytics & Support Enhancement (BASE) programme. We investigated the effects of the programme on the attitudes towards dementia care among professionals. METHOD: Forty-six participants in Japan received training in August 2016. The ongoing monitoring and assessment system was introduced to the participants for repeated measures of challenging behaviour. A 1-day follow-up meeting for debriefing was also performed after two months. A baseline and follow-up questionnaire survey was administered to the participating caregivers using a Japanese version of the Approaches to Dementia Questionnaire (ADQ) and the Zarit Burden Interview (ZBI). RESULTS: A significant improvement was observed in the total ADQ score among the participating caregivers from baseline to follow-up assessment. There was no significant difference between the baseline and follow-up assessment in the ZBI scores. In the follow-up meeting, several participants reported challenges and suggested solutions in facilitating a discussion on an action plan among professionals from various organizations. CONCLUSION: The implementation of the programme resulted in enhanced attitudes towards dementia care among the participants without an increased burden of care. Future studies should examine the programme's effectiveness on the challenging behaviour of persons with dementia.

Apolipoprotein E genotypes and longevity across dementia disorders.

INTRODUCTION: The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied. METHODS: We used a data set on 2858 subjects (1098 AD, 260 vascular dementia [VaD], 145 mixed AD and VaD, 90 other dementia diagnoses, and 1265 controls) to examine the association of APOE polymorphisms with clinical dementia diagnoses, biomarker profiles, and longevity. RESULTS: The ε4 allele was associated with reduced longevity as ε4 versus ε3 homozygotes lived on average 2.6 years shorter (P = .006). In AD, ε4 carriers lived 1.0 years shorter than noncarriers (P = .028). The ε4 allele was more prevalent in AD, mixed AD and VaD, and VaD patients compared to controls, but not in other dementia disorders. DISCUSSION: The APOE ε4 allele is influential in AD but might also be of importance in VaD and in mixed AD and VaD, diseases in which concomitant AD pathology is common.

The interactive effect of demographic and clinical factors on hippocampal volume: A multicohort study on 1958 cognitively normal individuals.

Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.

N-Terminal Prosomatostatin and Risk of Vascular Dementia.

BACKGROUND: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults. METHODS: In the prospective population-based Malmö Preventive Project, 5,347 study participants (mean age: 69 ± 6years; 70% men) provided plasma for the determination of NT-proSST concentration. Of these, 373 participants (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) during a follow-up period of 4.6 ± 1.3 years. The association of NT-proSST with the risk of dementia and its subtypes was studied using multivariable-adjusted Cox regression models controlling for age, gender, body mass index, systolic blood pressure, antihypertensive treatment, smoking, diabetes, lipid levels and prevalent stroke. RESULTS: Higher levels of NT-proSST were significantly associated with an increased risk of vascular dementia (hazard ratio [HR] per 1 SD: 1.29; 95% CI 1.05-1.59; p = 0.016), whereas no association was observed with Alzheimer's disease (HR per 1 SD: 0.99; 95% CI 0.81-1.20; p = 0.91), all-cause dementia (HR per 1 SD: 1.04; 95% CI 0.94-1.16; p = 0.44), and mixed dementia (HR per 1 SD: 0.98; 95% CI 0.79-1.21; p = 0.84). Levels of NT-proSST above 563 pmol/L (highest quartile) conferred distinctly increased risk of vascular dementia (HR 1.66; 95% CI 1.05-2.63; p = 0.029) compared with lower values. CONCLUSIONS: Higher levels of circulating N-terminal-prosomatostatin are associated with increased incidence of vascular dementia. Our findings might be of importance for the understanding of dementia development in older adults.

Longitudinal and postural changes of blood pressure predict dementia: the Malmö Preventive Project.

The role of blood pressure (BP) changes in dementia is debatable. We aimed to analyse how resting and postural BP changes relate to incident dementia over a long-term follow-up. In the prospective population-based Malmö Preventive Project, 18,240 study participants (mean age: 45 ± 7 years, 63% male) were examined between 1974 and 1992 with resting and standing BP measurement, and re-examined between 2002 and 2006 at mean age of 68 ± 6 years with resting BP. A total of 428 participants (2.3%) were diagnosed with dementia through Dec 31, 2009. The association of resting and postural BP changes with risk of dementia was studied using multivariable-adjusted Cox regression models controlling for traditional risk factors. Diastolic BP (DBP) decrease on standing indicated higher risk of dementia [Hazard ratio (HR) per 10 mmHg: 1.22; 95% confidence interval (CI) 1.01-1.44, p = 0.036], which was mainly driven by increased risk in normotensive individuals. Higher systolic (SBP) and diastolic BP at re-examination was associated with lower risk of dementia (HR per 10 mmHg: 0.94; 95% CI 0.89-0.99, p = 0.011; and 0.87; 0.78-0.96, p = 0.006, respectively). Extreme decrease in SBP/DBP between baseline and re-examination (4th quartile; -7 ± 12/-15 ± 7 mmHg, respectively) indicated higher risk of dementia (HR 1.46; 95% CI 1.11-1.93, p = 0.008, and 1.54; 95% CI 1.14-2.08, p = 0.005; respectively) compared with reference group characterised by pronounced BP increase over the same period (1st quartile; +44 ± 13/+15 ± 7 mmHg). Diastolic BP decrease on standing in the middle age, decline in BP between middle-and advanced age, and lower BP in advanced age are independent risk factors of developing dementia.

Cerebrospinal fluid tau and amyloid-ß1-42 in patients with dementia.

Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-ß1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-ß1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-ß1-42 and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-ß1-42 and amyloid-ß1-42:phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-ß1-42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-ß1-42 was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with Lewy bodies and Parkinson's disease dementia groups 53%, 34%, 67% and 53% of the subjects, respectively had abnormal amyloid-ß1-42 levels, 41%, 41%, 28% and 28% had abnormal total tau levels, and 29%, 28%, 25% and 19% had abnormal phosphorylated tau levels. Cerebrospinal fluid biomarkers were strongly associated with specific clinical dementia diagnoses with Alzheimer's disease and frontotemporal dementia showing the greatest difference in biomarker levels. In addition, cerebrospinal fluid amyloid-ß1-42, total tau, phosphorylated tau and the amyloid-ß1-42:phosphorylated tau ratio all correlated with poor cognitive performance in Alzheimer's disease, as did cerebrospinal fluid amyloid-ß1-42 in Parkinson's disease dementia and vascular dementia. The results support the use of cerebrospinal fluid biomarkers to differentiate between dementias in clinical practice, and to estimate disease severity.

Benchmarking biomarker-based criteria for Alzheimer's disease: Data from the Swedish Dementia Registry, SveDem.

INTRODUCTION: New research guidelines for the diagnosis of Alzheimer's disease (AD) include biomarker evidence of amyloid-ß (Aß) and tau pathology. The aim of this study was to investigate what proportion of AD patients diagnosed in clinical routine in Sweden that had an AD-indicative cerebrospinal fluid (CSF) biomarker profile. METHODS: By cross-referencing a laboratory database with the Swedish Dementia Registry (SveDem), 2357 patients with data on CSF Aß and tau biomarkers and a clinical diagnosis of AD with dementia were acquired. RESULTS: Altogether, 77.2% had pathologic Aß42 and total tau or phosphorylated tau in CSF. These results were stable across age groups. Female sex and low mini-mental state examination score increased the likelihood of pathologic biomarkers. DISCUSSION: About a quarter of clinically diagnosed AD patients did not have an AD-indicative CSF biomarker profile. This discrepancy may partly reflect incorrect (false positive) clinical diagnosis or a lack in sensitivity of the biomarker assays.

Changes in cerebrospinal fluid and blood plasma levels of IGF-II and its binding proteins in Alzheimer's disease: an observational study.

BACKGROUND: The Insulin-like Growth Factor (IGF)-related system is implicated in neuroregeneration and cell repair, as well as regulating lifespan. IGF-II, one component of this system, has also been found to affect memory functions in a rat model. In this study we explored changes in the IGF-related system in patients with Alzheimer's disease (AD), including changes in IGF-II levels. METHODS: We measured blood plasma and cerebrospinal fluid (CSF) levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in 72 healthy controls and 92 patients with AD. RESULTS: We found significantly lower blood plasma levels of IGF-II and IGFBP-3 in patients with AD, compared with controls. The levels of IGF-II and IGFBP-2 were significantly elevated in the CSF from patients with AD. We also found correlations between established CSF biomarkers for AD (tau and P-tau) and components of the IGF system. CONCLUSIONS: CSF and blood plasma levels of IGF-II and some of its binding proteins are changed in patients with AD. Further investigation into this area may unravel important clues to the nature of this disease.

Orthostatic Hypotension and Cognitive Function in Individuals 85 Years of Age: A Longitudinal Cohort Study in Sweden.

Orthostatic hypotension (OH) is more common in the elderly and associated with increased mortality. However, its implications for 85-year-olds are not known. In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH. Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality. OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.

Immigration and access to dementia diagnostics and treatment: A nationwide study in Sweden.

•Compared to Swedish-born people, foreign-born people were less likely to receive dementia diagnostic tests.•Being born in Africa or Europe was associated with lower chance of receiving cholinesterase inhibitors.•Asian-born people had higher chance of receiving cholinesterase inhibitors, but were less likely to receive memantine.•Disparities existed in dementia diagnostics and treatment between Swedish-born and foreign-born people, but were not consistent after adjusting for MMSE scores.

Associations of modifiable and non-modifiable risk factors with cognitive functions - a prospective, population-based, 17 years follow-up study of 3,229 individuals.

BACKGROUND: Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. METHODS: Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA1c), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions. RESULTS: The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3-20.8) years. When examining independent effects, APOE ε4 genotype(p < 0.01), and higher HbA1c(p < 0.001), were associated with future low memory function. Higher BMI (p < 0.05), and HbA1c(p < 0.05), lower high-density lipoprotein cholesterol (HDL-C)(p < 0.05)and stroke(p < 0.001) were associated with future low attention/executive function. The strongest factors associated with both better memory and attention/executive functions were higher education and alcohol consumption. Further, significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among ɛ4-carriers(p < 0.05). For attention/executive function, the protective effects of alcohol were greater among ɛ2 or ɛ4-carriers(p < 0.05). Also, attention/executive function was lower among ɛ4-carriers with higher BMI(p < 0.05) and ɛ2-carriers with higher HbA1c-levels(p < 0.05). CONCLUSIONS: Targeting cardiovascular risk factors in mid-life could have greater effect on future attention/executive functions rather than memory, whereas targeting diabetes could be beneficial for multiple cognitive domains. In addition, effects of different risk factors may vary depending on the APOE genotype. The varied cognitive profiles suggest that different mechanisms and brain regions are affected by the individual risk factors. Having detailed knowledge about the specific cognitive effects of different risk factors might be beneficial in preventive health counseling.