Association of cognitive reserve with transitions across cognitive states and death in older adults: A 15-year follow-up study.

INTRODUCTION: We investigated the association of cognitive reserve (CR) with transitions across cognitive states and death. METHODS: This population-based cohort study included 2631 participants (age ≥60 years) who were dementia-free at baseline and regularly examined up to 15 years. Data were analyzed using the Markov multistate models. RESULTS: Each 1-point increase in the composite CR score (range: -4.25 to 3.46) was significantly associated with lower risks of transition from normal cognition to cognitive impairment, no dementia (CIND) (multivariable-adjusted hazards ratio = 0.78; 95% confidence interval = 0.72-0.85) and death (0.85; 0.79-0.93), and from CIND to death (0.82; 0.73-0.91), but not from CIND to normal cognition or dementia. A greater composite CR score was associated with a lower risk of transition from CIND to death in people aged 60-72 but not in those aged ≥ 78 years. DISCUSSION: CR contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. HIGHLIGHTS: We use Markov multistate model to examine the association between cognitive reserve and transitions across cognitive states and death. A great cognitive reserve contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. A great cognitive reserve is associated with a lower risk of transition from cognitive impairment, no dementia to death in people at the early stage of old age, but not in those at the late stage of old age.

Blood biomarkers of Alzheimer's disease in the community: Variation by chronic diseases and inflammatory status.

INTRODUCTION: We explored the variations of blood biomarkers of Alzheimer's disease (AD) by chronic diseases and systemic inflammation. METHODS: We explored the association of AD blood biomarkers with chronic diseases and systemic inflammation (interleukin-6 [IL-6]), in 2366 dementia-free participants of the Swedish National Study on Aging and Care-in Kungsholmen, using quantile regression models. RESULTS: A greater number of co-occurring chronic diseases was associated with higher concentrations of phosphorylated-tau 181 (p-tau181), total-tau (t-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) (p < 0.01). Anemia, kidney, cerebrovascular, and heart diseases were associated with variations in the levels of AD blood biomarkers. Participants in the highest (vs. lowest) interleukin-6 (IL-6) tertile had higher NfL concentration. Systemic inflammation amplified the associations between several chronic diseases and p-tau181, t-tau, NfL, and GFAP. DISCUSSION: In the community, the concentration of AD blood biomarkers varies in relation to medical conditions and systemic inflammation. Recognizing these influences is crucial for the accurate interpretation and clinical implementation of blood biomarkers. HIGHLIGHTS: Participants with a complex clinical profile (i.e., multiple co-occurring diseases or specific disease combinations) display elevated levels of AD blood-biomarkers. Anemia, heart, cerebrovascular, and kidney diseases are associated with variations is the levels of AD blood biomarkers in cognitively intact older adults. Systemic inflammation amplifies the association between several chronic diseases and AD blood biomarkers.

Association of mild and complex multimorbidity with structural brain changes in older adults: A population-based study.

INTRODUCTION: We quantified the association of mild (ie, involving one or two body systems) and complex (ie, involving ≥3 systems) multimorbidity with structural brain changes in older adults. METHODS: We included 390 dementia-free participants aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen who underwent brain magnetic resonance imaging at baseline and after 3 and/or 6 years. Using linear mixed models, we estimated the association between multimorbidity and changes in total brain tissue, ventricular, hippocampal, and white matter hyperintensities volumes. RESULTS: Compared to non-multimorbid participants, those with complex multimorbidity showed the steepest reduction in total brain (ß*time -0.03, 95% CI -0.05, -0.01) and hippocampal (ß*time -0.05, 95% CI -0.08, -0.03) volumes, the greatest ventricular enlargement (ß*time 0.03, 95% CI 0.01, 0.05), and the fastest white matter hyperintensities accumulation (ß*time 0.04, 95% CI 0.01, 0.07). DISCUSSION: Multimorbidity, particularly when involving multiple body systems, is associated with accelerated structural brain changes, involving both neurodegeneration and vascular pathology. HIGHLIGHTS: Multimorbidity accelerates structural brain changes in cognitively intact older adults These brain changes encompass both neurodegeneration and cerebrovascular pathology The complexity of multimorbidity is associated with the rate of brain changes' progression.

The age-dependent association of Life's Simple 7 with transitions across cognitive states after age 60.

BACKGROUND: Life's Simple 7 (LS7) aims to promote ideal cardiovascular health (CVH). Its association with different cognitive states in the older old is unclear. OBJECTIVES: To assess the associations of LS7 with transitions across normal cognition, cognitive impairment, no dementia (CIND), and dementia and evaluate cognitive impairment-free years of life by LS7-defined CVH levels in older adults. METHODS: This cohort study included 2746 participants from the Swedish National Study on Aging and Care in Kungsholmen, regularly examined over 15 years. Total LS7 scores were created and dichotomized into worse and better CVH categories. The associations of LS7 total scores and CVH categories with cognitive states were assessed with multistate models in the whole sample and in younger old (<78 years) and older old adults (≥78 years) separately. Cognitive impairment-free life years by CVH categories were then predicted. RESULTS: A 1-point increment in the LS7 total score was associated with lower dementia risk in younger old adults (hazard ratio: 0.87 [0.78-0.97]) but not in older old adults (1.04 [0.97-1.13]). Better CVH was also associated with a lower risk of transition from normal cognition to CIND (0.76 [0.61-0.95]) and from normal cognition to dementia (0.42 [0.21-0.82]) in younger old adults. In younger old adults, those with better CVH were predicted to have two-to-three more cognitive impairment-free life years than those with worse CVH. CONCLUSION: Maintaining LS7-defined ideal CVH seems relevant in younger old adults but not in older old adults when considering the potential protective effects against cognitive impairment.

Multimorbidity patterns and 18-year transitions from normal cognition to dementia and death: A population-based study.

BACKGROUND: Several chronic diseases accelerate cognitive decline; however, it is still unknown how different patterns of multimorbidity influence individuals' trajectories across the cognitive continuum. OBJECTIVES: We aimed to investigate the impact of multimorbidity and of specific multimorbidity patterns on the transitions across cognitive stages (normal cognition, cognitive impairment, no dementia [CIND], dementia) and death. METHODS: We included 3122 dementia-free individuals from the Swedish National study on Aging and Care in Kungsholmen. Using fuzzy c-means cluster analysis, multimorbid participants were classified into mutually exclusive groups characterized by commonly coexisting chronic diseases. Participants were followed up to 18 years to detect incident CIND, dementia, or death. Transition hazard ratios (HRs), life expectancies, and time spent in different cognitive stages were estimated using multistate Markov models. RESULTS: At baseline, five multimorbidity patterns were identified: neuropsychiatric, cardiovascular, sensory impairment/cancer, respiratory/metabolic/musculoskeletal, and unspecific. Compared to the unspecific pattern, the neuropsychiatric and sensory impairment/cancer ones showed reduced hazards of reverting from CIND to normal cognition (HR 0.53, 95% CI 0.33-0.85 and HR 0.60, 95% CI 0.39-0.91). Participants in the cardiovascular pattern exhibited an increased hazard of progression from CIND to dementia (HR 1.70, 95% CI 1.15-2.52) and for all transitions to death. Subjects with the neuropsychiatric and cardiovascular patterns showed reduced life expectancy at age 75, with an anticipation of CIND (up to 1.6 and 2.2 years, respectively) and dementia onset (up to 1.8 and 3.3 years, respectively). CONCLUSIONS: Multimorbidity patterns differentially steer individual trajectories across the cognitive continuum of older adults and may be used as a risk stratification tool.

Markers of olfactory dysfunction and progression to dementia: A 12-year population-based study.

INTRODUCTION: We evaluated markers of olfactory dysfunction (OD) for estimating hazard of dementia in older adults. METHODS: Mild (hyposmia) and severe (anosmia) OD was classified in a population-based study of dementia-free persons (SNAC-K; n = 2473; mean age = 70 years) using the Sniffin sticks odor identification task. Combined variables were created for objective and subjective OD and for OD and APOE status. Hazard of dementia across 12 years was estimated with Cox regression. RESULTS: OD was associated with increased hazard of dementia (2.01; 95% confidence interval [CI] 1.60-2.52), with the strongest association for anosmia (2.92; 95% CI 2.14-3.98). Results remained consistent after adjusting for potential confounders and across age and sex subgroups. APOE ε4 carriers with anosmia had the highest hazard of dementia (ε4: 6.95; 95% CI 4.16-11.62; ε4/ε4: 19.84; 95% CI 6.17-63.78). DISCUSSION: OD is associated with increased risk of dementia, especially severe impairment in combination with genetic risk of Alzheimer's disease.

Association of ischemic heart disease with long-term risk of cognitive decline and dementia: A cohort study.

INTRODUCTION: The independent and joint effect of ischemic heart disease (IHD) and coexisting atrial fibrillation (AF) and heart failure (HF) on dementia risk is largely unknown. METHODS: This population-based cohort study included 2568 dementia-free participants (age ≥60 years) in SNAC-K, who were regularly examined from 2001-2004 through 2013-2016. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. Global cognitive function was assessed using a global cognitive composite z-score derived from five cognitive domains. Data were analyzed using Cox, Fine-Gray, and linear mixed-effects models. RESULTS: Overall, IHD at baseline was associated with multivariable-adjusted hazard ratio (HR) of 1.39 (95% confidence interval = 1.06-1.82) for dementia and multivariable-adjusted ß-coefficient of -0.02 (-0.03 to -0.01) for annual changes in global cognitive z-score, independent of AF, HF, and cerebrovascular disease. Coexisting AF or HF did not add further risk to dementia and cognitive decline. DISCUSSION: IHD is independently associated with dementia and cognitive decline in older adults, whereas coexisting AF/HF is not associated with an increased risk. HIGHLIGHTS: Is a history of ischemic heart disease (IHD) associated with a risk for dementia? How do coexisting heart diseases affect this association? IHD was an independent risk factor for dementia in older adults. This association was independent of coexisting heart and cerebrovascular diseases. The coexistence of heart diseases did not confer additional risk for dementia.

A glycan epitope correlates with tau in serum and predicts progression to Alzheimer's disease in combination with APOE4 allele status.

INTRODUCTION: There is an urgent need for novel blood biomarkers for the detection of Alzheimer's disease (AD). We previously showed that levels of the bisecting N-acetylglucosamine glycan epitope was elevated in cerebrospinal fluid in AD. However, its diagnostic value in blood is unknown. METHODS: We analyzed blood levels of bisecting N-acetylglucosamine and total tau in a retrospective cohort of 233 individuals. Progression to AD was compared between the groups using Cox regression. The predictive value of the biomarkers was determined by logistic regression. RESULTS: Bisecting N-acetylglucosamine correlated with tau levels (p < 0.0001). Individuals with an intermediate tau/bisecting N-acetylglucosamine ratio had elevated AD risk (hazard ratio = 2.06, 95% confidence interval [CI]: 1.18-3.6). Moreover, a combined model including tau/bisecting N-acetylglucosamine ratio, apolipoprotein E (APOE) ε4 status, and Mini-Mental State Examination score predicted future AD (area under the curve = 0.81, 95% CI: 0.68-0.93). DISCUSSION: Bisecting N-acetylglucosamine in combination with tau is a valuable blood biomarker for predicting AD.

Mild cognitive impairment among rural-dwelling older adults in China: A community-based study.

BACKGROUND: Epidemiological studies of mild cognitive impairment (MCI) and subtypes of MCI have rarely focused on rural residents in China. METHODS: This population-based study included 5068 participants (age ≥60 years) who were living in rural communities. We defined MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) following the Petersen's criteria that integrated neuropsychological assessments with in-person clinical evaluations. RESULTS: The overall prevalence of MCI, aMCI, and naMCI was 26.48%, 22.30%, and 4.18%, respectively. The prevalence of MCI increased with age. The adjusted odds ratio (OR) of MCI was 0.71 (95% confidence interval [CI] 0.61 to 0.82) for primary school (vs. illiteracy), 0.30 (0.24 to 0.39) for middle school or above, 1.35 (1.09 to 1.67) for being farmers, 0.65 (0.54 to 0.78) for alcohol consumption, 1.43 (1.20 to 1.70) for stroke history, and 1.14 (0.95 to 1.36) for any apolipoprotein E (APOE) ε4 allele (vs ε3/ε3). CONCLUSIONS: MCI affects over one-fourth of rural older adults in China. Overall MCI was associated with demographic factors, non-alcohol consumption, and stroke, but not with APOE genotype and cardiometabolic factors.

Development and internal validation of a prognostic model for 15-year risk of Alzheimer dementia in primary care patients.

BACKGROUND: The exploitation of routinely collected clinical health information is warranted to optimize the case detection and diagnostic workout of Alzheimer's disease (AD). We aimed to derive an AD prediction score based on routinely collected primary care data. METHODS: We built a cohort selecting 199,978 primary care patients 60 + part of the Health Search Database between January 2002 and 2009, followed up until 2019 to detect incident AD cases. The cohort was randomly divided into a derivation and validation sub-cohort. To identify AD and non-AD cases, we applied a clinical algorithm that involved two clinicians. According to a nested case-control design, AD cases were matched with up to 10 controls based on age, sex, calendar period, and follow-up duration. Using the derivation sub-cohort, 32 potential AD predictors (sociodemographic, clinical, drug-related, etc.) were tested in a logistic regression and selected to build a prediction model. The predictive performance of this model was tested on the validation sub-cohort by mean of explained variation, calibration, and discrimination measurements. RESULTS: We identified 3223 AD cases. The presence of memory disorders, hallucinations, anxiety, and depression and the use of NSAIDs were associated with future AD. The combination of the predictors allowed the production of a predictive score that showed an explained variation (pseudo-R2) for AD occurrence of 13.4%, good calibration parameters, and an area under the curve of 0.73 (95% CI: 0.71-0.75). In accordance with this model, 7% of patients presented with a high-risk score for developing AD over 15 years. CONCLUSION: An automated risk score for AD based on routinely collected clinical data is a promising tool for the early case detection and timely management of patients by the general practitioners.

Trajectories of cognitive decline and dementia development: A 12-year longitudinal study.

INTRODUCTION: Mapping the preclinical dementia phase is important for early detection and evaluation of interventions. We assessed the trajectories of cognitive decline in preclinical dementia over 12 years and investigated whether being a fast decliner across 6 years is associated with increased risk of dementia the following 6 years. METHODS: Rates of cognitive decline were determined using mixed-effects models for 1646 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) cohort. Cox regression was used to assess the future likelihood of dementia for fast decliners (declining ≥1.5 standard deviations [SDs] faster than the age-specific rates). RESULTS: Participants in a preclinical phase of dementia showed increased rates of decline in all cognitive tests compared to the no-dementia group, particularly closer (0-6 years) to diagnosis. Participants declining fast in three or more cognitive tests 12-6 years before diagnosis demonstrated a high risk of dementia 6 years later (hazard ratio [HR] 3.90, 95% confidence interval [CI] 2.28-6.69). DISCUSSION: Being a fast decliner is linked to increased risk of future dementia.

Association of resting heart rate with cognitive decline and dementia in older adults: A population-based cohort study.

INTRODUCTION: Resting heart rate (RHR) predicts future risk for cardiovascular disease (CVD). However, longitudinal studies investigating the relationship of RHR with cognitive decline are scarce. METHODS: This population-based cohort study included 2147 participants (age≥60) in SNAC-K who were free of dementia and regularly followed from 2001-2004 to 2013-2016. RHR was assessed with electrocardiogram. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders 4th Revision criteria. Global cognitive function was assessed using Mini-Mental State Examination (MMSE). Data were analyzed using Cox and linear mixed-effects models. RESULTS: RHR≥80 (vs. 60-69) bpm was associated with a multi-adjusted hazard ratio of 1.55 (95% confidence interval 1.06-2.27) for dementia. The association remained significant after excluding participants with prevalent and incident CVDs. Similarly, RHR≥80 bpm was associated with a multi-adjusted ß-coefficient of -0.13 (-0.21 to -0.04) for MMSE score. DISCUSSION: Higher RHR is associated with increased risk for dementia and faster cognitive decline independent of CVDs in a general population of elderly people.

Cardiometabolic multimorbidity accelerates cognitive decline and dementia progression.

INTRODUCTION: Cardiometabolic diseases (CMDs) have been individually associated with adverse cognitive outcomes, but their combined effect has not been investigated. METHODS: A total of 2577 dementia-free participants 60 years of age or older were followed for 12 years to observe changes in cognitive function and to detect incident cognitive impairment, no dementia (CIND) and dementia. CMDs (including type 2 diabetes, heart disease, and stroke) were assessed at baseline through medical records and clinical examinations. Cardiometabolic multimorbidity was defined as the presence of two or more CMDs. Data were analyzed using multi-adjusted linear mixed-effects models, Cox regression, and Laplace regression. RESULTS: CMD multimorbidity was associated with cognitive decline, CIND (hazard ratio [HR] 1.73; 95% confidence interval CI 1.23 to 2.44), and its progression to dementia (HR 1.86; 95% CI 1.17 to 2.97). CMD multimorbidity accelerated the onset of CIND by 2.3 years and dementia by 1.8 years. CONCLUSIONS: CMD multimorbidity accelerates cognitive decline and increases the risk of both CIND and its conversion to dementia. HIGHLIGHTS: We explored the combined impact of cardiometabolic diseases (CMDs) on cognition. An increasing number of CMDs dose-dependently accelerated cognitive decline. CMD multimorbidity increased the risk of both cognitive impairment and dementia. Co-morbid CMDs could be ideal targets for interventions to protect cognitive health.

The impact of diabetes on cognitive impairment and its progression to dementia.

INTRODUCTION: Diabetes is a well-established risk factor for dementia, but its impact on the prodromal phase of dementia is unclear. METHODS: Cohorts of older adults who were cognitively healthy (n = 1840) or had cognitive impairment-no dementia (CIND; n = 682) were followed over 12 years to detect incident CIND and dementia, respectively. RESULTS: Poorly controlled diabetes (glycated hemoglobin [HbA1c] ≥7.5%; reference = normoglycemia) was associated with double the risk of CIND (Cox regression multi-adjusted hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.13-3.58) and triple the risk CIND progressing to dementia (HR 2.87, 95% CI 1.20-6.85). Co-morbid diabetes and heart disease doubled the risk of incident CIND and dementia, although neither disease conferred a significant risk of either outcome alone. Elevated systemic inflammation contributed to the diabetes-associated increased dementia risk. CONCLUSIONS: Diabetes characterized by poor glycemic control or cardiovascular complications is related to a greater risk of the development and progression of cognitive impairment. Inflammation may play a role in these relationships.

Multimorbidity burden and dementia risk in older adults: The role of inflammation and genetics.

INTRODUCTION: We investigate dementia risk in older adults with different disease patterns and explore the role of inflammation and apolipoprotein E (APOE) genotype. METHODS: A total of 2,478 dementia-free participants with two or more chronic diseases (ie, multimorbidity) part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) were grouped according to their multimorbidity patterns and followed to detect clinical dementia. The potential modifier effect of C-reactive protein (CRP) and apolipoprotein E (APOE) genotype was tested through stratified analyses. RESULTS: People with neuropsychiatric, cardiovascular, and sensory impairment/cancer multimorbidity had increased hazards for dementia compared to the unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13-2.42; 1.61, 95% CI 1.17-2.29; 1.32, 95% CI 1.10-1.71, respectively). Despite the lack of statistically significant interaction, high CRP increased dementia risk within these patterns, and being APOE ε4 carriers heightened dementia risk for neuropsychiatric and cardiovascular multimorbidity. DISCUSSION: Individuals with neuropsychiatric, cardiovascular, and sensory impairment/cancer patterns are at increased risk for dementia and APOE ε4, and inflammation may further increase the risk. Identifying such high-risk groups might allow tailored interventions for dementia prevention.

Detection and Prediction of Incident Alzheimer Dementia over a 10-Year or Longer Medical History: A Population-Based Study in Primary Care.

BACKGROUND: Despite the crucial role played by general practitioners in the identification and care of people with cognitive impairment, few data are available on how they may improve the early recognition of patients with Alzheimer dementia (AD), especially those with long (i.e., 10 years and longer) medical history. AIMS: To investigate the occurrence and the predictors of AD during a 10-year or longer period prior AD diagnosis in primary care patients aged 60 years or older. MATERIALS AND METHODS: A cohort study with a nested case-control analysis has been conducted. Data were extracted from the Italian Health Search Database (HSD), an Italian database with primary care data. AD cases have been defined in accordance with the International Classification of Diseases, ninth edition (ICD-9-CM) codes and coupled with the use of anti-dementia drugs. Prevalence and incidence rates of AD have been calculated. To test the association between candidate predictors, being identified in a minimum period of 10 years, and incident cases of AD, we used a multivariate conditional logistic regression model. RESULTS: As recorded in the primary care database, AD prevalence among patients aged 60 years or older was 0.8% during 2016, reaching 2.4% among nonagenarians. Overall, 1,889 incident cases of AD have been identified, with an incidence rate as high as 0.09% person-year. Compared with 18,890 matched controls, history of hallucinations, agitation, anxiety, aberrant motor behavior, and memory deficits were positively associated with higher odds of AD (p < 0.001 for all) diagnosis. A previous diagnosis of depression and diabetes and the use of low-dose aspirin and non-steroidal anti-inflammatory drugs were associated with higher odds of AD (p < 0.05 for all). CONCLUSION: Our findings show that, in accordance with primary care records, 1% of patients aged 60 years and older have a diagnosis of AD, with an incident AD diagnosis of 0.1% per year. AD is often under-reported in primary care settings; yet, several predictors identified in this study may support general practitioners to early identify patients at risk of AD.

The impact of delirium on outcomes for older adults hospitalised with COVID-19.

INTRODUCTION: Delirium is a frequent condition in hospitalized older patients and it usually has a negative prognostic value. A direct effect of SARS-COV-2 on the central nervous system (CNS) has been hypothesized. OBJECTIVE: To evaluate the presence of delirium in older patients admitted for a suspected diagnosis of COVID-19 and its impact on in-hospital mortality. SETTING AND SUBJECTS: 91 patients, aged 70-years and older, admitted to an acute geriatric ward in Northern Italy from March 8th to April 17th, 2020. METHODS: COVID-19 cases were confirmed by reverse transcriptase-polymerase chain reaction assay for SARS-Cov-2 RNA from nasal and pharyngeal swabs. Delirium was diagnosed by two geriatricians according to the Diagnostic and Statistical Manual of Mental Disorders V (DMS V) criteria. The number of chronic diseases was calculated among a pre-defined list of 60. The pre-disease Clinical Frailty Scale (CFS) was assessed at hospital admission. RESULTS: Of the total sample, 39 patients died, 49 were discharged and 3 were transferred to ICU. Twenty-five patients (27.5%) had delirium. Seventy-two percent of patients with delirium died during hospitalization compared to 31.8% of those without delirium. In a multivariate logistic regression model adjusted for potential confounders, patients with delirium were four times more likely to die during hospital stay compared to those without delirium (OR = 3.98;95%CI = 1.05-17.28; p = 0.047). CONCLUSIONS: Delirium is common in older patients with COVID-19 and strongly associated with in-hospital mortality. Regardless of causation, either due to a direct effect of SARS-COV-2 on the CNS or to a multifactorial cause, delirium should be interpreted as an alarming prognostic indicator in older people.

Disability trajectories and mortality in older adults with different cognitive and physical profiles.

BACKGROUND: Cognitive and physical deficits independently raise the risk for negative events in older adults. Less is known about whether their co-occurrence constitutes a distinct risk profile. This study quantifies the association between cognitive impairment, no dementia (CIND), slow walking speed (WS) and their combination and disability and mortality. METHODS: We examined 2546 dementia-free people aged ≥ 60 years, part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) up to 12 years. The following four profiles were created: (1) healthy profile; (2) isolated CIND (scoring 1.5 SD below age-specific means on at least one cognitive domain); (3) isolated slow WS (< 0.8 m/s); (4) CIND+ slow WS. Disability was defined as the sum of impaired activities of daily living and trajectories of disability were derived from mixed-effect linear regression models. Piecewise proportional hazard models were used to estimate mortality rate [hazard ratios (HRs)]. Population attributable risks of death were calculated. RESULTS: Participants with both CIND and slow WS had the worst prognosis, especially in the short-term period. They experienced the steepest increase in disability and five times the mortality rate (HR 5.1; 95% CI 3.5-7.4) of participants free from these conditions. Similar but attenuated results were observed for longer follow-ups. Co-occurring CIND and slow WS accounted for 30% of short-term deaths. CONCLUSIONS: Co-occurring cognitive and physical limitations constitute a distinct risk profile in older people, and account for a large proportion of short-term deaths. Assessing cognitive and physical function could enable early identification of people at high risk for adverse events.

Untangling the relationship between fat distribution, nutritional status and Parkinson's disease severity.

BACKGROUND: Parkinson's disease (PD) is responsible for significant changes in body composition. AIMS: We aimed to test the association between PD severity and fat distribution patterns, and to investigate the potential modifier effect of nutritional status in this association. METHODS: We enrolled 195 PD subjects consecutively admitted to a university geriatric day hospital. All participants underwent comprehensive clinical evaluation, including assessment of total and regional body composition (dual-energy X-ray absorptiometry, DXA), body mass index, nutritional status (Mini-Nutritional Assessment, MNA), motor disease severity (UPDRS III), comorbidities, and pharmacotherapy. RESULTS: The fully adjusted linear regression model showed a negative association between UPDRS III and total body fat in kg and percentage (respectively, B - 0.79; 95% CI - 1.54 to - 0.05 and B - 0.55; 95% CI - 1.04 to - 0.05), percentage android fat (B - 1.07; 95% CI - 1.75 to - 0.39), trunk-leg fat ratio (B - 0.02; 95% CI - 0.04 to - 0.01), trunk-limb fat ratio (B - 0.01; 95% CI - 0.06 to - 0.01) and android-gynoid fat ratio (B - 0.01; 95% CI - 0.03 to - 0.01). After stratification by MNA score, all the parameters of android-like fat distribution resulted negatively associated (p < 0.001 for all) with UPDRS III, but only among subjects with a MNA < 23.5 (risk of malnutrition or malnutrition). CONCLUSION: We found a negative association between severity of motor impairment and total fat mass in PD, more specific with respect to an android pattern of fat distribution. This association seems to be driven by nutritional status, and is significant only among patients at risk of malnutrition or with overt malnutrition.

Tracing temporal trends in dementia incidence over 25 years in central Stockholm, Sweden.

INTRODUCTION: Recent reports from high-income countries have suggested a declining incidence of dementia. METHODS: Trends in dementia incidence over 25 years among people ≥75 years of age were examined using two population-based cohort studies: the Kungsholmen Project (KP, n = 1473, 1987-1998) and the Swedish National study on Aging and Care in Kungsholmen (SNAC-K, n = 1746, 2001-2013). RESULTS: We identified 440 (29.9%) and 388 (22.2%) incident dementia cases in the KP and SNAC-K cohorts, respectively. The incidence of dementia declined by 30% (hazard ratio [HR] = 0.70; 95% confidence interval [CI] 0.61-0.80) during the second decade. Adjustment of education, psychosocial working conditions, lifestyle, and vascular diseases did not substantially change the results (HR = 0.77, 95% CI 0.65-0.90). This decline was observed particularly in women and people with elementary education. DISCUSSION: Our study provides direct evidence of a declining trend in dementia incidence. Improved cognitive reserve and cardiovascular health could partially explain the decline.