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

Author

Payton, Nicola M., Marseglia, Anna, Grande, Giulia, Fratiglioni, Laura, Kivipelto, Miia, Bäckman, Lars, Laukka, Erika J., Payton, Nicola M., Marseglia, Anna, Grande, Giulia, Fratiglioni, Laura, Kivipelto, Miia, Bäckman, Lars, and Laukka, Erika J.

Abstract

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.

Published
2022
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55. Cardiometabolic multimorbidity accelerates cognitive decline and dementia progression

Author

Dove, Abigail, Marseglia, Anna, Shang, Ying, Grande, Giulia, Vetrano, Davide Liborio, Laukka, Erika J., Fratiglioni, Laura, Xu, Weili, Dove, Abigail, Marseglia, Anna, Shang, Ying, Grande, Giulia, Vetrano, Davide Liborio, Laukka, Erika J., Fratiglioni, Laura, and Xu, Weili

Abstract

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.

Published
2022
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56. Association Between Late-Life Weight Change and Dementia : A Population-based Cohort Study

Author

Guo, Jie, Marseglia, Anna, Shang, Ying, Dove, Abigail, Grande, Giulia, Fratiglioni, Laura, Xu, Weili, Guo, Jie, Marseglia, Anna, Shang, Ying, Dove, Abigail, Grande, Giulia, Fratiglioni, Laura, and Xu, Weili

Abstract

Background: The impact of late-life weight changes on incident dementia is unclear. We aimed to investigate the associations of body mass index (BMI) and weight changes with dementia and to explore the role of APOE ɛ4 in these associations. Methods: A total of 1 673 dementia-free participants aged ≥60 and older were followed for an initial 6 years to detect changes in BMI/weight and then for an additional 6 years to detect incident dementia. BMI change ([BMIfirst 6-year follow-up - BMIbaseline]/BMIbaseline) was categorized as stable (≤5%), and moderate (5%-10%) or large (>10%) gain or loss. Weight change (weightfirst 6-year follow-up - weightbaseline) was categorized as stable (≤2.5 kg), and moderate (2.5-7.5 kg) or large (>7.5 kg) gain or loss. Dementia was diagnosed following standard criteria. Data were analyzed using Cox regression models. Results: Over the second 6-year follow-up period, 102 incident dementia cases were identified. Compared with stable BMI, the hazard ratios (95% CI) of dementia were 2.61 (1.09-5.54) and 2.93 (1.72-4.91) for BMI gain or loss >10%, respectively. The risk of dementia was higher among APOE ɛ4 carriers experiencing a large BMI gain (9.93 [3.49-24.6]) or loss (6.66 [2.83-14.4]) than APOE ɛ4 noncarriers with stable BMI. Similar results were observed for weight change and dementia associations. Conclusions: BMI and weight changes showed U-shaped associations with dementia risk. Large bodyweight gain and loss alike are associated with an almost 3-fold higher risk of dementia, which may be amplified by APOE ɛ4.

Published
2022
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57. Migraine, Cognitive Decline, and Dementia in Older Adults : A Population-Based Study

Author

Liang, Yajun, Gao, Ya, Wang, Rui, Grande, Giulia, Monastero, Roberto, Dong, Yanhong, Jiang, Xin, Lv, Peiyuan, Qiu, Chengxuan, Liang, Yajun, Gao, Ya, Wang, Rui, Grande, Giulia, Monastero, Roberto, Dong, Yanhong, Jiang, Xin, Lv, Peiyuan, and Qiu, Chengxuan

Abstract

Background: The potential impact of migraine on cognitive aging among older adults remains controversial.Objective:To examine the relationship of migraine and subtypes with cognitive decline and dementia in an older Swedish population. Methods: This population-based study included 3,069 participants (age ≥ 60 years) from the Swedish National study on Aging and Care in Kungsholmen, Stockholm. Baseline examination was conducted in 2001–2004, and participants were followed every 3 or 6 years until 2013–2016. Data were collected through face-to-face interviews, clinical examinations, laboratory tests, and linkage with registers. Global cognitive function was measured with the Mini-Mental State Examination (MMSE). Dementia was diagnosed according to the DSM-IV criteria. Migraine and subtypes were defined following the international classification system. Data were analyzed using logistic regression, Cox regression, and linear mixed-effects models. Results: At baseline, 305 participants were defined with non-migraine headache and 352 with migraine. The cross-sectional analysis showed that the multivariable-adjusted odds ratio (95% confidence interval) of prevalent dementia was 0.49 (0.20–1.21) for migraine and 0.66 (0.26–1.66) for migraine without aura. The longitudinal analysis showed that the multivariable-adjusted hazard ratios of incident dementia associated with migraine and subtypes ranged 0.68–0.89 (p > 0.05). Furthermore, migraine and subtypes were not significantly associated with either baseline MMSE score or MMSE changes during follow-ups (p > 0.05). The nonsignificant associations did not vary substantially by age, APOE ɛ4 allele, cerebrovascular disease, and antimigraine treatment (p for interactions > 0.05). Conclusion: This study shows no evidence supporting the associations of migraine and its subtypes with cognitive decline and dementia among older adults.

Published
2022
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58. Primary care costs due to prodromal Alzheimer disease : a real-world study in patients with a 10-year or longer medical history

Author

Vetrano, Davide L., Grande, Giulia, Mazzoleni, Francesco, Lovato, Valeria, Cricelli, Claudio, Lapi, Francesco, Vetrano, Davide L., Grande, Giulia, Mazzoleni, Francesco, Lovato, Valeria, Cricelli, Claudio, and Lapi, Francesco

Abstract

Background: The aim of this study was to estimate primary care costs of prodromal signs/symptoms of Alzheimer disease (AD), during a 10-year or longer period preceding AD diagnosis, in relation to costs cumulated in the general population for the same reasons. Methods: Nested case-control study involving 1889 AD cases and 18,890 controls aged 60+ from the Italian primary care Health Search Database (HSD). AD incident cases were through the International Classification of Diseases, 9th edition. Costs related to drugs, diagnostic tests and specialist referrals triggered by prodromal AD signs and/or symptoms were quantified and compared with costs cumulated by non-AD counterparts. Results: During the pre-diagnosis 10-year or longer period, prodromal signs and symptoms trigger diagnostic and therapeutic costs 55% higher than those cumulated in general population for the same clinical reasons. After accounting for patients' comorbidity and regional differences, the mean cost related to diagnostic and therapeutic procedures, and those related to specialist referrals, amounted to 854.1 euro(SD: 630.6 euro) in AD incident cases vs. 527.3 euro(SD: 446.2) cumulated in patients not developing AD. Conclusion: Prodromal AD manifestations are associated with primary care costs that resulted higher than those cumulated in the general population aged 60+. It remains to be elucidated if earlier dementia diagnoses would be associated with reduced costs triggered by the same clinical signs and symptoms.

Published
2022
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59. Environmental Air Pollution and Olfactory Decline in Aging

Author

Ekström, Ingrid, Rizzuto, Debora, Grande, Giulia, Bellander, Tom, Laukka, Erika J., Ekström, Ingrid, Rizzuto, Debora, Grande, Giulia, Bellander, Tom, and Laukka, Erika J.

Abstract

BACKGROUND: Olfactory impairment is increasingly common with older age, which may be in part explained by cumulative effects of exposure to inhaled toxins. However, population-based studies investigating the relationship between air pollution and olfactory ability are scarce. OBJECTIVES: We aimed to investigate associations between exposure to common air pollutants and longitudinal change in odor identification. METHODS: Our study of 2,468 participants (mean age = 72.3 y; 61.1% female), of which 1,774 participants (mean age = 70.5 y; 61.9% female) had at least two olfactory assessments over 12 y of follow-up from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), Stockholm, Sweden. Participants were free from cognitive impairment and neurodegenerative disease at baseline. Odor identification ability was assessed with Sniffin' Sticks. Change in olfactory performance was estimated with linear mixed models. Exposure to two major airborne pollutants [particulate matter with aerodynamic diameter <= 2.5 mu m (PM2.5) and nitrogen oxides (NOx)] for the 5 y preceding baseline was assessed using spatiotemporal dispersion models for outdoor levels at residential addresses. RESULTS: Participants showed significant decline in odor identification ability for each year in the study {f3 = - 0.20 [95% confidence interval (CI): -0.22, 0.18; p < 0.001]}. After adjustment for all covariates, residents of third [f3= - 0.09 (95% CI: -0.14, -0.04; p < 0.001)] and fourth [f3 = - 0.07 (95% CI: -0.12, -0.02; p = 0.005)] exposure quartiles of PM2.5 had faster rates of olfactory decline than residents from the first quartile. Similar results were observed for the third [f3= - 0.05 (95% CI: -0.10, -0.01; p = 0.029)] and fourth [f3= - 0.07 (95% CI: -0.11, -0.02; p = 0.006) quartiles of NOx]. DISCUSSION: Our results suggest an association between air pollution exposure and subsequent olfactory decline. We speculate that cumulative effects of airborne pollutants on the

Published
2022
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60. Air pollution as a risk factor for Cognitive Impairment no Dementia (CIND) and its progression to dementia : A longitudinal study

Author

Wu, Jing, Grande, Giulia, Stafoggia, Massimo, Ljungman, Petter, Laukka, Erika J., Eneroth, Kristina, Bellander, Tom, Rizzuto, Debora, Wu, Jing, Grande, Giulia, Stafoggia, Massimo, Ljungman, Petter, Laukka, Erika J., Eneroth, Kristina, Bellander, Tom, and Rizzuto, Debora

Abstract

Background and aim: Accumulation of evidence has raised concern regarding the harmful effect of air pollution on cognitive function, but results are diverging. We aimed to investigate the longitudinal association of long-term exposure to air pollutants and cognitive impairment and its further progression to dementia in older adults residing in an urban area. Methods: Data were obtained from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Cognitive impairment, no dementia (CIND) was assessed by a comprehensive neuropsychological battery (scoring >= 1.5 standard deviations below age-specific means in >= 1 cognitive domain). We assessed long-term residential exposure to particulate matters (PM2.5 and PM10) and nitrogen oxides (NOx) with dispersion modeling. The association with CIND was estimated using Cox proportional hazards models with 3-year moving average air pollution exposure. We further estimated the effect of long-term air pollution exposure on the progression of CIND to dementia using Cox proportional hazards models. Results: Among 1987 cognitively intact participants, 301 individuals developed CIND during the 12-year followup. A 1-mu g/m(3) increment in PM2.5 exposure was associated with a 75% increased risk of incident CIND (HR = 1.75, 95 %CI: 1.54, 1.99). Weaker associations were found for PM10 (HR for 1-mu g/m(3) = 1.08, 95 %CI: 1.03-1.14) and NOx (HR for 10 mu g/m(3) = 1.18, 95 %CI: 1.04-1.33). Among those with CIND at baseline (n = 607), 118 participants developed dementia during follow-up. Results also show that exposure to air pollution was a risk factor for the conversion from CIND to dementia (PM2.5: HR for 1-mu g/m(3) = 1.90, 95 %CI: 1.48-2.43; PM10 : HR for 1-mu g/m(3) = 1.14, 95 %CI: 1.03-1.26; and NOR: HR for 10 mu g/m(3) = 1.34, 95 %CI: 1.07-1.69). Conclusion: We found evidence of an association between long-term exposure to ambient air pollutants and incidence of CIND. Of special interest is that air pollution also

Published
2022
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61. Impact of Pneumonia on Cognitive Aging : A Longitudinal Propensity-Matched Cohort Study

Author

Hendel, Merle K., Rizzuto, Debora, Grande, Giulia, Calderón-Larrañaga, Amaia, Laukka, Erika J., Fratiglioni, Laura, Vetrano, Davide L., Hendel, Merle K., Rizzuto, Debora, Grande, Giulia, Calderón-Larrañaga, Amaia, Laukka, Erika J., Fratiglioni, Laura, and Vetrano, Davide L.

Abstract

Background: Acute clinical events, such as pneumonia, may impact physical functionality but their effect on cognition and the possible duration of this effect remains to be quantified. This study investigated the impact of pneumonia on cognitive trajectories and dementia development in older people. Methods: Data were obtained from 60+ years old individuals, who were assessed from 2001 to 2018 in the population-based SNAC-K study (Sweden). Participants were eligible if they were not institutionalized, had no dementia, and did not experience pneumonia 5 years prior to baseline (N = 2 063). A propensity score was derived to match 1:3 participants hospitalized with a diagnosis of pneumonia (N = 178), to nonexposed participants (N = 534). Mixed linear models were used to model cognitive decline. The hazard of dementia, clinically diagnosed by physicians following Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, was estimated using Cox regression models. Results: We found a transient impact of pneumonia on cognitive decline in the first 2.5 years (B = −0.94, 95% confidence interval [CI] −1.75, −0.15). The hazard ratio (HR) for dementia was not statistically significantly increased in pneumonia participants (HR = 1.17, 95%CI 0.82, 1.66). Conclusions: The transient impact of pneumonia on cognitive function suggests an increased need of health care for patients after a pneumonia-related hospitalization and reinforces the relevance of pneumonia prevention.

Published
2022
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62. Pulse, Shunt and Storage: Hydrological Contraction Shapes Processing and Export of Particulate Organic Matter in River Networks

Author

Catalán, Núria, del Campo, Rubén, Talluto, Matthew, Mendoza-Lera, Clara, Grande, Giulia, Bernal, Susana, Von Schiller, D., Singer, Gabriel, Bertuzzo, E., Catalán, Núria, del Campo, Rubén, Talluto, Matthew, Mendoza-Lera, Clara, Grande, Giulia, Bernal, Susana, Von Schiller, D., Singer, Gabriel, and Bertuzzo, E.

Abstract

Streams and rivers act as landscape-scale bioreactors processing large quantities of terrestrial particulate organic matter (POM). This function is linked to their flow regime, which governs residence times, shapes organic matter reactivity and controls the amount of carbon (C) exported to the atmosphere and coastal oceans. Climate change impacts flow regimes by increasing both flash floods and droughts. Here, we used a modelling approach to explore the consequences of lateral hydrological contraction, that is, the reduction of the wet portion of the streambed, for POM decomposition and transport at the river network scale. Our model integrates seasonal leaf litter input as generator of POM, transient storage of POM on wet and dry streambed portions with associated decomposition and ensuing changes in reactivity, and transport dynamics through a dendritic river network. Simulations showed that the amount of POM exported from the river network and its average reactivity increased with lateral hydrological contraction, due to the combination of (1) low processing of POM while stored on dry streambeds, and (2) large shunting during flashy events. The sensitivity analysis further supported that high lateral hydrological contraction leads to higher export of higher reactivity POM, regardless of transport coefficient values, average reactivity of fresh leaf litter and differences between POM reactivity under wet and dry conditions. Our study incorporates storage in dry streambed areas into the pulse-shunt concept (Raymond and others in Ecology 97(1):5–16, 2016. https://doi.org/10.1890/ 14-1684.1), providing a mechanistic framework and testable predictions about leaf litter storage, transport and decomposition in fluvial networks.

Published
2022

67. Cognitive, Genetic, Brain Volume, and Diffusion Tensor Imaging Markers as Early Indicators of Dementia

Author

Müller, Theresa, Payton, Nicola M., Kalpouzos, Grégoria, Jessen, Frank, Grande, Giulia, Bäckman, Lars, and Laukka, Erika J.

Subjects
cognition, Male, Aging, psychology [Dementia], methods [Diffusion Tensor Imaging], Apolipoproteins E, genetics [Dementia], psychology [Aging], magnetic resonance imaging, Humans, ddc:610, diagnostic imaging [Dementia], diagnostic imaging [Brain], Aged, Aged, 80 and over, physiology [Cognition], preclinical dementia, Brain, Organ Size, Middle Aged, diffusion tensor imaging, Early Diagnosis, genetics [Aging], genetics [Apolipoproteins E], Dementia, Female, white matter, APOE, Research Article
Abstract

Background: Although associated with dementia and cognitive impairment, microstructural white matter integrity is a rarely used marker of preclinical dementia. Objective: We aimed to evaluate the individual and combined effects of multiple markers, with special focus on microstructural white matter integrity, in detecting individuals with increased dementia risk. Methods: A dementia-free subsample (n = 212, mean age = 71.33 years) included in the population-based Swedish National Study on Aging and Care (SNAC-K) underwent magnetic resonance imaging (T1-weighted, fluid-attenuated inversion recovery, diffusion tensor imaging), neuropsychological testing (perceptual speed, episodic memory, semantic memory, letter and category fluency), and genotyping (APOE). Incident dementia was assessed during six years of follow-up. Results: A global model (global cognition, APOE, total brain tissue volume: AUC = 0.920) rendered the highest predictive value for future dementia. Of the models based on specific markers, white matter integrity of the forceps major tract was included in the most predictive model, in combination with perceptual speed and hippocampal volume (AUC = 0.911). Conclusion: Assessment of microstructural white matter integrity may improve the early detection of dementia, although the added benefit in this study was relatively small.

Published
2020

68. Cardiometabolic multimorbidity accelerates cognitive decline and dementia progression.

Author

Dove, Abigail, Marseglia, Anna, Shang, Ying, Grande, Giulia, Vetrano, Davide Liborio, Laukka, Erika J, Fratiglioni, Laura, and Xu, Weili

Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2023
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69. Trajectories of cognitive decline and dementia development: A 12‐year longitudinal study.

Author

Payton, Nicola M., Marseglia, Anna, Grande, Giulia, Fratiglioni, Laura, Kivipelto, Miia, Bäckman, Lars, and Laukka, Erika J.

Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2023
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70. Brain Changes and Fast Cognitive and Motor Decline in Older Adults.

Author

Grande, Giulia, Vetrano, Davide Liborio, Kalpouzos, Grégoria, Welmer, Anna-Karin, Laukka, Erika J, Marseglia, Anna, Fratiglioni, Laura, and Rizzuto, Debora

Subjects
*COGNITION disorders, *OLDER people, *DIFFUSION tensor imaging, *WALKING speed, *WHITE matter (Nerve tissue), *MINI-Mental State Examination
Abstract

Background To identify brain magnetic resonance imaging (MRI) signatures characterizing people with different patterns of decline in cognition and motor function. Methods In the Swedish National Study on Aging and Care in Kungsholmen, Stockholm, 385 participants had available repeated brain MRI examinations, where markers of brain volumes and white matter integrity were assessed. The speed of cognitive and motor decline was estimated as the rate of a Mini-Mental State Examination and gait speed decline over 12 years (linear mixed models), and further dichotomized into the upper (25% fastest rate of decline) versus the lower quartiles. Participants were grouped in slow/no decliners (reference), isolated motor decliners, isolated cognitive decliners, and cognitive and motor decliners. We estimated the associations between changes in brain markers (linear mixed models) and baseline diffusion tensor imaging measures (linear regression model) and the 4 decline patterns. Results Individuals with concurrent cognitive and motor decline (n  = 51) experienced the greatest loss in the total brain (β: −12.3; 95% confidence interval [CI]: −18.2; −6.38) and hippocampal (β: −0.25; 95% CI: −0.34; −0.16) volumes, the steepest accumulation of white matter hyperintensities (β: 1.61; 95% CI: 0.54; 2.68), and the greatest ventricular enlargement (β: 2.07; 95% CI: 0.67; 3.47). Compared to the reference, those only experiencing cognitive decline presented with steeper hippocampal volume loss, whereas those exhibiting only motor decline displayed a greater white matter hyperintensities burden. Lower microstructural white matter integrity was associated with concurrent cognitive and motor decline. Conclusion Concurrent cognitive and motor decline is accompanied by rapidly evolving and complex brain pathology involving both gray and white matter. Isolated cognitive and motor declines seem to exhibit brain damage with different qualitative features. [ABSTRACT FROM AUTHOR]

Published
2023
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71. Association Between Late-Life Weight Change and Dementia: A Population-based Cohort Study.

Author

Guo, Jie, Marseglia, Anna, Shang, Ying, Dove, Abigail, Grande, Giulia, Fratiglioni, Laura, and Xu, Weili

Subjects
DEMENTIA, BODY mass index, COHORT analysis, DISEASE risk factors, APOLIPOPROTEIN E
Abstract

Background The impact of late-life weight changes on incident dementia is unclear. We aimed to investigate the associations of body mass index (BMI) and weight changes with dementia and to explore the role of APOE ɛ4 in these associations. Methods A total of 1 673 dementia-free participants aged ≥60 and older were followed for an initial 6 years to detect changes in BMI/weight and then for an additional 6 years to detect incident dementia. BMI change ([BMIfirst 6-year follow-up − BMIbaseline]/BMIbaseline) was categorized as stable (≤5%), and moderate (5%–10%) or large (>10%) gain or loss. Weight change (weightfirst 6-year follow-up − weightbaseline) was categorized as stable (≤2.5 kg), and moderate (2.5–7.5 kg) or large (>7.5 kg) gain or loss. Dementia was diagnosed following standard criteria. Data were analyzed using Cox regression models. Results Over the second 6-year follow-up period, 102 incident dementia cases were identified. Compared with stable BMI, the hazard ratios (95% CI) of dementia were 2.61 (1.09−5.54) and 2.93 (1.72−4.91) for BMI gain or loss >10%, respectively. The risk of dementia was higher among APOE ɛ4 carriers experiencing a large BMI gain (9.93 [3.49−24.6]) or loss (6.66 [2.83−14.4]) than APOE ɛ4 noncarriers with stable BMI. Similar results were observed for weight change and dementia associations. Conclusions BMI and weight changes showed U-shaped associations with dementia risk. Large bodyweight gain and loss alike are associated with an almost 3-fold higher risk of dementia, which may be amplified by APOE ɛ4. [ABSTRACT FROM AUTHOR]

Published
2023
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72. Mild cognitive impairment among rural‐dwelling older adults in China: A community‐based study

Author

Cong, Lin, primary, Ren, Yifei, additional, Wang, Yongxiang, additional, Hou, Tingting, additional, Dong, Yi, additional, Han, Xiaojuan, additional, Yin, Ling, additional, Zhang, Qinghua, additional, Feng, Jianli, additional, Wang, Lidan, additional, Tang, Shi, additional, Grande, Giulia, additional, Laukka, Erika J., additional, Du, Yifeng, additional, and Qiu, Chengxuan, additional

Published
2022
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78. Cognitive and physical markers of prodromal dementia: A 12‐year‐long population study

Author

Grande, Giulia, Rizzuto, Debora, Vetrano, Davide L., Marseglia, Anna, Vanacore, Nicola, Laukka, Erika J., Welmer, Anna‐Karin, and Fratiglioni, Laura

Subjects
Male, Sweden, Featured Articles, Prodromal Symptoms, Walking, Featured Article, walking speed, Neuropsychological Tests, Healthy Volunteers, clinical markers, mental disorders, Humans, Dementia, Female, Longitudinal Studies, Cognition Disorders, human activities, cognitive impairment, population‐based study, Aged
Abstract

Introduction The aim is to test whether adding a simple physical test such as walking speed (WS) to the neuropsychological assessment increases the predictive ability to detect dementia. Methods The 2546 dementia‐free people from the SNAC‐K study were grouped into four profiles: (1) healthy profile; (2) isolated cognitive impairment, no dementia (CIND, scoring 1.5 standard deviation below age‐specific means on ≥1 cognitive domains); (3) isolated slow WS (

Published
2020

85. From Normal Cognition to Cognitive Impairment and Dementia: Impact of Orthostatic Hypotension

Author

Xia, Xin, Wang, Rui, Vetrano, Davide L., Grande, Giulia, Laukka, Erika J., Ding, Mozhu, Fratiglioni, Laura, and Qiu, Chengxuan

Subjects
Aged, 80 and over, Male, hypotension, population, Original Articles, Middle Aged, Neuropsychological Tests, orthostatic, Hypotension, Orthostatic, Cognition, cohort studies, Cognitive Aging, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Humans, Cognitive Dysfunction, Dementia, Female, Orthostatic Hypotension, Aged
Abstract

Supplemental Digital Content is available in the text., The role of orthostatic hypotension (OH) in the continuum of cognitive aging remains to be clarified. We sought to investigate the associations of OH with dementia, cognitive impairment, no dementia (CIND), and CIND progression to dementia in older adults while considering orthostatic symptoms. This population-based cohort study included 2532 baseline (2001–2004) dementia-free participants (age ≥60 years; 62.6% women) in the SNAC-K (Swedish National Study on Aging and Care in Kungsholmen) who were regularly examined over 12 years. We further divided the participants into a baseline CIND-free cohort and a CIND cohort. OH was defined as a decrease by ≥20/10 mm Hg in systolic/diastolic blood pressure upon standing and further divided into asymptomatic and symptomatic OH. Dementia was diagnosed following the international criteria. CIND was defined as scoring ≥1.5 SDs below age group-specific means in ≥1 cognitive domain. Data were analyzed with flexible parametric survival models, controlling for confounding factors. Of the 2532 participants, 615 were defined with OH at baseline, and 322 were diagnosed with dementia during the entire follow-up period. OH was associated with an adjusted hazard ratio of 1.40 for dementia (95% CI, 1.10–1.76), 1.15 (0.94–1.40) for CIND, and 1.54 (1.05–2.25) for CIND progression to dementia. The associations of dementia and CIND progression to dementia with asymptomatic OH were similar to overall OH, whereas symptomatic OH was only associated with CIND progression to dementia. Our study suggests that OH, even asymptomatic OH, is associated with increased risk of dementia and accelerated progression from CIND to dementia in older adults.

Published
2021

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

Author

Imahori, Yume, Vetrano, Davide L., Xia, Xin, Grande, Giulia, Ljungman, Petter, Fratiglioni, Laura, and Qiu, Chengxuan

Abstract

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 β‐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. [ABSTRACT FROM AUTHOR]

Published
2022
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88. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

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de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernández, I, Montrreal, L, Antúnez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, González-Perez, A, Calero, M, Franco-Macías, E, Macías, J, Blesa, R, Cervera-Carles, L, Menéndez-González, M, Frank-García, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, García-Madrona, S, García-González, P, Alarcón-Martín, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Pérez-Cordón, A, Benussi, A, Rábano, A, Padovani, A, Squassina, A, de Mendonça, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gómez, A, Martín Montes, A, Sanabria, Á, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Ståhlbom, A, Tybjærg-Hansen, A, Hartmann, A, Spottke, A, Corbatón-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martínez Rodríguez, C, Muñoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grünblatt, E, Dardiotis, E, Düzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Küçükali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbæk, G, Ortega, G, Chêne, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fließbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Löwenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sánchez-Arjona, M, Dalmasso, M, Martínez-Larrad, M, Arcaro, M, Nöthen, M, Fernández-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossù, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hägg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, Del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Kehoe, P, Garcia-Ribas, G, Sánchez-Juan, P, Pastor, P, Pérez-Tur, J, Piñol-Ripoll, G, Lopez de Munain, A, García-Alberca, J, Bullido, M, Álvarez, V, Lleó, A, Real, L, Mir, P, Medina, M, Scheltens, P, Holstege, H, Marquié, M, Sáez, M, Carracedo, Á, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sánchez-Valle, R, Serrano-Ríos, M, Orellana, A, Tárraga, L, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, Clarimón, J, Boada, M, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, Ruiz, A, de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E, Pedersen, Nancy L, Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M, Bis, Joshua C, Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C, Lemstra, Afina W, Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A L, Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anas, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L, Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M, Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G, Kunkle, Brian W, Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B, Chillotti, Caterina, Reynolds, Chandra A, Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L, Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K, Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L, Vogelgsang, Jonathan, Pineda, Juan A, Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A, Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M Arfan, Deniz-Naranjo, M Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A, Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M, Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J, Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H, Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T, Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M, Seidu, Nazib M, Banaj, Nerisa, Armstrong, Nicola J, Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Hoffmann, Per, Holmans, Peter A, Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N, Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, Del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A L, Andreoni, Simona, Ferrarese, Carlo, Sala Gessica, Zoia, Chiara Paola, Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J, Álvarez, Victoria, Lleó, Alberto, Real, Luis M, Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D, Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M, Mather, Karen A, Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A, Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M, Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J, Ruiz, Agustín, de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernández, I, Montrreal, L, Antúnez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, González-Perez, A, Calero, M, Franco-Macías, E, Macías, J, Blesa, R, Cervera-Carles, L, Menéndez-González, M, Frank-García, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, García-Madrona, S, García-González, P, Alarcón-Martín, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Pérez-Cordón, A, Benussi, A, Rábano, A, Padovani, A, Squassina, A, de Mendonça, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gómez, A, Martín Montes, A, Sanabria, Á, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Ståhlbom, A, Tybjærg-Hansen, A, Hartmann, A, Spottke, A, Corbatón-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martínez Rodríguez, C, Muñoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grünblatt, E, Dardiotis, E, Düzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Küçükali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbæk, G, Ortega, G, Chêne, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fließbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Löwenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sánchez-Arjona, M, Dalmasso, M, Martínez-Larrad, M, Arcaro, M, Nöthen, M, Fernández-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossù, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hägg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, Del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Kehoe, P, Garcia-Ribas, G, Sánchez-Juan, P, Pastor, P, Pérez-Tur, J, Piñol-Ripoll, G, Lopez de Munain, A, García-Alberca, J, Bullido, M, Álvarez, V, Lleó, A, Real, L, Mir, P, Medina, M, Scheltens, P, Holstege, H, Marquié, M, Sáez, M, Carracedo, Á, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sánchez-Valle, R, Serrano-Ríos, M, Orellana, A, Tárraga, L, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, Clarimón, J, Boada, M, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, Ruiz, A, de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E, Pedersen, Nancy L, Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M, Bis, Joshua C, Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C, Lemstra, Afina W, Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A L, Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anas, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L, Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M, Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G, Kunkle, Brian W, Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B, Chillotti, Caterina, Reynolds, Chandra A, Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L, Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K, Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L, Vogelgsang, Jonathan, Pineda, Juan A, Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A, Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M Arfan, Deniz-Naranjo, M Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A, Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M, Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J, Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H, Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T, Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M, Seidu, Nazib M, Banaj, Nerisa, Armstrong, Nicola J, Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Hoffmann, Per, Holmans, Peter A, Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N, Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, Del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A L, Andreoni, Simona, Ferrarese, Carlo, Sala Gessica, Zoia, Chiara Paola, Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J, Álvarez, Victoria, Lleó, Alberto, Real, Luis M, Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D, Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M, Mather, Karen A, Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A, Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M, Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J, and Ruiz, Agustín

Abstract

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

Published
2021

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

Author

Grande, Giulia, Marengoni, Alessandra, Vetrano, Davide L., Roso-Llorach, Albert, Rizzuto, Debora, Zucchelli, Alberto, Qiu, Chengxuan, Fratiglioni, Laura, Calderón-Larrañaga, Amaia, Grande, Giulia, Marengoni, Alessandra, Vetrano, Davide L., Roso-Llorach, Albert, Rizzuto, Debora, Zucchelli, Alberto, Qiu, Chengxuan, Fratiglioni, Laura, and Calderón-Larrañaga, Amaia

Abstract

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 epsilon 4 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 epsilon 4, and inflammation may further increase the risk. Identifying such high-risk groups might allow tailored interventions for dementia prevention.

Published
2021
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90. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Author

Itziar de Rojas, Itziar, Grande, Giulia, Papenberg, Göran, van der Lee, Sven J., Ruiz, Agustín, Itziar de Rojas, Itziar, Grande, Giulia, Papenberg, Göran, van der Lee, Sven J., and Ruiz, Agustín

Abstract

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n=409,435 and validation size n=58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE 4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease. Known genetic loci account for only a fraction of the genetic contribution to Alzheimer's disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer's disease polygenic risk score.

Published
2021
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91. Health Trajectories in Swedish Centenarians

Author

Vetrano, Davide L., Grande, Giulia, Marengoni, Alessandra, Calderón-Larrañaga, Amaia, Rizzuto, Debora, Vetrano, Davide L., Grande, Giulia, Marengoni, Alessandra, Calderón-Larrañaga, Amaia, and Rizzuto, Debora

Abstract

Background: Longitudinal studies describing centenarians' health trajectories are currently lacking. We compared health trajectories of older adults becoming centenarians and their shorter-living counterparts in terms of chronic diseases, disability, and cognitive decline. Methods: We identified 3,573 individuals participating in the Kungsholmen Project and the Swedish National Study on Aging and Care in Kungsholmen who lived <100 years and 222 who survived to their 100th birthday. Trajectories of chronic diseases, disability (impaired activities of daily living), and cognitive status were obtained via linear mixed models over 13 years. Results: Centenarians had fewer chronic diseases than noncentenarians. Before age 85, centenarians showed slower health changes. In centenarians, multimorbidity, disability, and cognitive impairment occurred 4 to 9 years later than in noncentenarians. After age 85, the speed of accumulation of chronic diseases, disabilities, and cognitive decline accelerated in centenarians. At age 100, 39% of the centenarians were cognitively intact and 55% had escaped disability. Only 5% were free of multimorbidity at age 100. When compared with their shorter lived counterparts, in terms of years spent in poor health, centenarians experienced more years with multimorbidity (9.4 vs 6.8 years; p <.001), disability (4.3 vs 3.1 years; p =.005), and cognitive impairment (6.3 vs 4.3 years; p <.001). Conclusions: Older people who become centenarians present a delay in the onset of morbidity, but spend more years in this condition compared to their shorter lived peers. The observation of older adults' health trajectories might help to forecast healthier aging, and plan future medical and social care delivery.

Published
2021
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92. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Author

Instituto de Salud Carlos III, Grifols, La Caixa, European Research Council, Pérez-Tur, Jordi [0000-0002-9111-1712], Rojas, Itziar de, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, N. L., Stringa, N., Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Rossi, Giacomina, Tankard, R. M., Wiltfang, J., Giegling, Ina, Seidu, N. M., Dalmasso, Maria Carolina, Benussi, A., Boschi, Silvia, Sáez, María Eugenia, Binetti, Giuliano, Royo, José Luis, Pérez-Tur, Jordi, Spalletta, Gianfranco, Corbaton-Anchuelo, A., Froelich, L., Satizabal, Claudia L., Hagg, S., Ortega, G., Peters, Oliver, Vogelgsang, Jonathan, Serrano-Rios, M., Gil, S., Djurovic, Srdjan, Van Dongen, Jasper, Deramecourt, V., Kalaria, R. N., Wang, L. S., Goldhardt, O., Charbonnier, Camille, Farotti, Lucia, Kornhuber, Johannes, Andreassen, Ole A., Álvarez, Victoria, Herrmann, Martin J., Pasquier, Florence, Calero, Miguel, Holmes, Clive, Haapasalo, Annakaisa, Scherbaum, Norbert, Scheltens, Philip, Caffarra, P., Pineda, Juan A., Del Ser, Teodoro, Hort, Jakub, Espinosa, A., Bullido, María Jesús, Hampel, Harald, Medina, Miguel, Williams, Julie, Sims, Rebecca, Martinez-Larrad, M. T., Riederer, Peter, Esiri, M., Botne Sando, S., Grunblatt, E., Hoffmann, Per, Hiltunen, Mikko, Kern, Silke, Mendoza, Silvia, Kilander, Lena, Jessen, F., Ghidoni, R., Giedraitis, Vilmantas, Molina-Porcel, Laura, Sánchez-Juan, Pascual, Schmid, Matthias, van Duijn, Cornelia M., Antonell, A., Mir, Pablo, Moreno, F., Ferreira, Catarina B., Skrobot, Olivia, Sanchez-Valle, R., Chene, G., Duron, Emmanuelle, Martin Montes, Ángel, Ciccone, Simona, Piñol-Ripoll, Gerard, Ngandu, Tiia, Dardiotis, Efthimios, Scherer, Martin, Arosio, Beatrice, Meggy, A., Sotolongo-Grau, Oscar, Selbaek, Geir, Aarsland, D., Seshadri, Sudha, Bailly, Henri, Sánchez-García, Florentino, Roberto, Natalia, Armstrong, Nicola J., Farrer, Lindsay A., Popp, Julius, Riedel-Heller, Steffi, Fernández-Fuertes, Marta, Scamosci, Michela, Alcolea, Daniel, Rosas Allende, Irene, Marquié, Marta, Benussi, Luisa, Ewers, Michael, Antúnez, Carmen, van Broeckhoven, Christine, Masullo, C., Vyhnalek, Martin, Bossu, Paola, Appollonio, I., Mayeux, R., Lerch, Ondrej, Rábano, Alberto, Quenez, Olivier, Schneider, Anja, Wallon, David, Macías Sánchez, Juan, PGC-ALZ consortia, Yang, Q., Helisalmi, Seppo, Huisman, M., Lambert, Jean-Charles, Kehoe, Patrick G., Heneka, Michael T., DEGESCO consortium, Papenberg, Goran, Lowenmark, M., Frikke-Schmidt, Ruth, Fornage, Myriam, Kunkle, Brian W., Heilmann-Heimbach, Stefanie, Posthuma, Danielle, Tremolizzo, Lucio, Amouyel, Philippe, Franco-Macías, Emilio, Munoz-Fernandez, C., Sorbi, Sandro, Küçükali, Fahri, Dionigi Rossi, P., Huerto Vilas, Raquel, Spallazzi, Marco, Alarcón-Martín, Emilio, Maier, Wolfgang, de Mendonça, Alexandre, The GR@ACE study group, Benaque, Alba, EADB contributors, IGAP (ADGC, CHARGE, EADI, GERAD), van der Lee, Sven J., DeStefano, Anita, Lleó, Alberto, Kosmidis, Mary H., Rongve, A., Nicolas, Gael, Escott-Price, Valentina, Tybjaerg-Hansen, Anne, Chillotti, Caterina, Pastor, Pau, Buiza-Rueda, Dolores, Alegret, Montserrat, Lage, Carmen, Holmans, Peter A., Polak, Thomas, Pastor, Ana Belén, Nöthen, Markus M., García-Ribas, Guillermo, Pijnenburg, Yolande A L, Vidal, Jean-Sebastien, Squassina, Alessio, Kuulasmaa, Teemu, Pericak-Vance, M. A., Pisanu, Claudia, Fliessbach, Klaus, Grimmer, Timo, Galimberti, Daniela, Parnetti, L., López de Munain, Adolfo, Soininen, Hilkka, Carracedo, Ángel, Deckert, Jurgen, Karlsson, I. K., Buerger, Katharina, Clark, Christopher, Cecchetti, Roberta, Fostinelli, Silvia, Deniz-Naranjo, M. C., Engelborghs, S., Álvarez, Ignacio, Sakka, Paraskevi, Thomassen, Jesper Qvist, Ramirez, A., Holstege, Henne, Marshall, Rachel, Haines, Jonathan L., Hulsman, Marc, Kleineidam, Luca, Ferri, E., Pérez-Cordon, Alba, Menéndez-González, Manuel, van der Flier, Wiesje M., Rainero, Innocenzo, Rujescu, D., Wagner, Michael, Corma-Gómez, Anaïs, Lebouvier, T., Ruiz, Agustín, Vandenberghe, Rik, Weinhold, Leonie, Padovani, Alessandro, Diehl-Schmid, Janine, Mead, Simon, Fenoglio, Chiara, Conti, Elisa, Díez-Fairen, Mónica, Fischer, Peter, Abdelnour, Carla, Giaccone, G., González-Pérez, Antonio, Hartmann, Annette M., Hadjigeorgiou, Georgios, Zulaica, M., Sleegers, Kristel, Martínez Rodríguez, Carmen, García-González, Pablo, Rubino, Elisa, Bis, Joshua C., Orellana, Adelina, Zetterberg, Henrik, Schellenberg, Gerard D., Borroni, Barbara, Sanabria, Angela, Fortea, J., Reynolds, C. A., Gelpi, E., Bernal Sánchez-Arjona, María, Boerwinkle, Eric, Mather, K. A., Jian, X., Saltvedt, Ingvild, Frank-García, Ana, Rosende-Roca, Maitee, Kinhult Stahlbom, Anne, Hanon, Olivier, Skoog, Ingmar, Kivipelto, Miia, Lehtisalo, Jenni, García-Alberca, José María, Dufouil, Carole, Bellenguez, Celine, Ingelsson, Martin, Nacmias, B., Spottke, Annika, Ullgren, Abbe, Hausner, Lucrezia, Arias Pastor, Alfonso, Tsolaki, Magda, Seripa, Davide, Naj, A. C., Clarimón, Jordi, Nordestgaard, Borge G., Valero, Sergi, van Schoor, N. M., Scarpini, E., Graff, Caroline, Boada, Mercè, Tagliavini, F., Scarmeas, N., García-Madrona, Sebastián, Yannakoulia, Mary, Banaj, Nerisa, Blennow, Kaj, Duzel, Emrah, Tárraga, Lluís, Lemstra, A. W., Morgan, K., Kok, A. A. L., Bessi, Valentina, Baquero, Miquel, Rodríguez-Rodríguez, Eloy, Cervera-Carles, Laura, Archetti, Silvana, Grande, Giulia, Dichgans, Martin, Arcaro, Marina, Blesa, Rafael, Real, Luis Miguel, Ikram, M. Arfan, Mangialasche, Francesca, Quintela, Inés, Instituto de Salud Carlos III, Grifols, La Caixa, European Research Council, Pérez-Tur, Jordi [0000-0002-9111-1712], Rojas, Itziar de, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, N. L., Stringa, N., Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Rossi, Giacomina, Tankard, R. M., Wiltfang, J., Giegling, Ina, Seidu, N. M., Dalmasso, Maria Carolina, Benussi, A., Boschi, Silvia, Sáez, María Eugenia, Binetti, Giuliano, Royo, José Luis, Pérez-Tur, Jordi, Spalletta, Gianfranco, Corbaton-Anchuelo, A., Froelich, L., Satizabal, Claudia L., Hagg, S., Ortega, G., Peters, Oliver, Vogelgsang, Jonathan, Serrano-Rios, M., Gil, S., Djurovic, Srdjan, Van Dongen, Jasper, Deramecourt, V., Kalaria, R. N., Wang, L. S., Goldhardt, O., Charbonnier, Camille, Farotti, Lucia, Kornhuber, Johannes, Andreassen, Ole A., Álvarez, Victoria, Herrmann, Martin J., Pasquier, Florence, Calero, Miguel, Holmes, Clive, Haapasalo, Annakaisa, Scherbaum, Norbert, Scheltens, Philip, Caffarra, P., Pineda, Juan A., Del Ser, Teodoro, Hort, Jakub, Espinosa, A., Bullido, María Jesús, Hampel, Harald, Medina, Miguel, Williams, Julie, Sims, Rebecca, Martinez-Larrad, M. T., Riederer, Peter, Esiri, M., Botne Sando, S., Grunblatt, E., Hoffmann, Per, Hiltunen, Mikko, Kern, Silke, Mendoza, Silvia, Kilander, Lena, Jessen, F., Ghidoni, R., Giedraitis, Vilmantas, Molina-Porcel, Laura, Sánchez-Juan, Pascual, Schmid, Matthias, van Duijn, Cornelia M., Antonell, A., Mir, Pablo, Moreno, F., Ferreira, Catarina B., Skrobot, Olivia, Sanchez-Valle, R., Chene, G., Duron, Emmanuelle, Martin Montes, Ángel, Ciccone, Simona, Piñol-Ripoll, Gerard, Ngandu, Tiia, Dardiotis, Efthimios, Scherer, Martin, Arosio, Beatrice, Meggy, A., Sotolongo-Grau, Oscar, Selbaek, Geir, Aarsland, D., Seshadri, Sudha, Bailly, Henri, Sánchez-García, Florentino, Roberto, Natalia, Armstrong, Nicola J., Farrer, Lindsay A., Popp, Julius, Riedel-Heller, Steffi, Fernández-Fuertes, Marta, Scamosci, Michela, Alcolea, Daniel, Rosas Allende, Irene, Marquié, Marta, Benussi, Luisa, Ewers, Michael, Antúnez, Carmen, van Broeckhoven, Christine, Masullo, C., Vyhnalek, Martin, Bossu, Paola, Appollonio, I., Mayeux, R., Lerch, Ondrej, Rábano, Alberto, Quenez, Olivier, Schneider, Anja, Wallon, David, Macías Sánchez, Juan, PGC-ALZ consortia, Yang, Q., Helisalmi, Seppo, Huisman, M., Lambert, Jean-Charles, Kehoe, Patrick G., Heneka, Michael T., DEGESCO consortium, Papenberg, Goran, Lowenmark, M., Frikke-Schmidt, Ruth, Fornage, Myriam, Kunkle, Brian W., Heilmann-Heimbach, Stefanie, Posthuma, Danielle, Tremolizzo, Lucio, Amouyel, Philippe, Franco-Macías, Emilio, Munoz-Fernandez, C., Sorbi, Sandro, Küçükali, Fahri, Dionigi Rossi, P., Huerto Vilas, Raquel, Spallazzi, Marco, Alarcón-Martín, Emilio, Maier, Wolfgang, de Mendonça, Alexandre, The GR@ACE study group, Benaque, Alba, EADB contributors, IGAP (ADGC, CHARGE, EADI, GERAD), van der Lee, Sven J., DeStefano, Anita, Lleó, Alberto, Kosmidis, Mary H., Rongve, A., Nicolas, Gael, Escott-Price, Valentina, Tybjaerg-Hansen, Anne, Chillotti, Caterina, Pastor, Pau, Buiza-Rueda, Dolores, Alegret, Montserrat, Lage, Carmen, Holmans, Peter A., Polak, Thomas, Pastor, Ana Belén, Nöthen, Markus M., García-Ribas, Guillermo, Pijnenburg, Yolande A L, Vidal, Jean-Sebastien, Squassina, Alessio, Kuulasmaa, Teemu, Pericak-Vance, M. A., Pisanu, Claudia, Fliessbach, Klaus, Grimmer, Timo, Galimberti, Daniela, Parnetti, L., López de Munain, Adolfo, Soininen, Hilkka, Carracedo, Ángel, Deckert, Jurgen, Karlsson, I. K., Buerger, Katharina, Clark, Christopher, Cecchetti, Roberta, Fostinelli, Silvia, Deniz-Naranjo, M. C., Engelborghs, S., Álvarez, Ignacio, Sakka, Paraskevi, Thomassen, Jesper Qvist, Ramirez, A., Holstege, Henne, Marshall, Rachel, Haines, Jonathan L., Hulsman, Marc, Kleineidam, Luca, Ferri, E., Pérez-Cordon, Alba, Menéndez-González, Manuel, van der Flier, Wiesje M., Rainero, Innocenzo, Rujescu, D., Wagner, Michael, Corma-Gómez, Anaïs, Lebouvier, T., Ruiz, Agustín, Vandenberghe, Rik, Weinhold, Leonie, Padovani, Alessandro, Diehl-Schmid, Janine, Mead, Simon, Fenoglio, Chiara, Conti, Elisa, Díez-Fairen, Mónica, Fischer, Peter, Abdelnour, Carla, Giaccone, G., González-Pérez, Antonio, Hartmann, Annette M., Hadjigeorgiou, Georgios, Zulaica, M., Sleegers, Kristel, Martínez Rodríguez, Carmen, García-González, Pablo, Rubino, Elisa, Bis, Joshua C., Orellana, Adelina, Zetterberg, Henrik, Schellenberg, Gerard D., Borroni, Barbara, Sanabria, Angela, Fortea, J., Reynolds, C. A., Gelpi, E., Bernal Sánchez-Arjona, María, Boerwinkle, Eric, Mather, K. A., Jian, X., Saltvedt, Ingvild, Frank-García, Ana, Rosende-Roca, Maitee, Kinhult Stahlbom, Anne, Hanon, Olivier, Skoog, Ingmar, Kivipelto, Miia, Lehtisalo, Jenni, García-Alberca, José María, Dufouil, Carole, Bellenguez, Celine, Ingelsson, Martin, Nacmias, B., Spottke, Annika, Ullgren, Abbe, Hausner, Lucrezia, Arias Pastor, Alfonso, Tsolaki, Magda, Seripa, Davide, Naj, A. C., Clarimón, Jordi, Nordestgaard, Borge G., Valero, Sergi, van Schoor, N. M., Scarpini, E., Graff, Caroline, Boada, Mercè, Tagliavini, F., Scarmeas, N., García-Madrona, Sebastián, Yannakoulia, Mary, Banaj, Nerisa, Blennow, Kaj, Duzel, Emrah, Tárraga, Lluís, Lemstra, A. W., Morgan, K., Kok, A. A. L., Bessi, Valentina, Baquero, Miquel, Rodríguez-Rodríguez, Eloy, Cervera-Carles, Laura, Archetti, Silvana, Grande, Giulia, Dichgans, Martin, Arcaro, Marina, Blesa, Rafael, Real, Luis Miguel, Ikram, M. Arfan, Mangialasche, Francesca, and Quintela, Inés

Abstract

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

Published
2021

93. Physical activity and exercise in dementia: an umbrella review of intervention and observational studies

Author

Demurtas, Jacopo, Schoene, Daniel, Torbahn, Gabriel, Petrovic, Mirko, Maggi, Stefania, Cesari, Matteo, Lamb, Sarah, Marengoni, Alessandra, Soysal, Pınar, Sieber, Cornel, Shenkin, Susan, Schwingshack, Lukas, Grande, Giulia, Smith, Lee, Veronese, Nicola, and SOYSAL, PINAR

Subjects
Alzheimer, Dementia
Abstract

Objectives The aim of this umbrella review was to determine the effect of physical activity/exercise on improving cognitive and noncognitive outcomes in people with MCI (mild cognitive impairment) and dementia. Design Umbrella review of systematic reviews (SR), with or without meta-analyses (MAs), of randomized controlled trials (RCTs) and observational studies. Settings and Participants People with MCI or dementia, confirmed through validated assessment measures. Any form of physical activity/exercise was included. As controls, we included participants not following any prespecified physical activity/exercise intervention or following the same standard protocol with the intervention group. Methods The protocol was registered in PROSPERO (CDR 164197). Major databases were searched until December 31, 2019. The certainty of evidence of statistically significant outcomes was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. SRs' findings, without a formal MA, were reported descriptively. Results Among 1160 articles initially evaluated, 27 SRs (all of RCTs, 9 without MA) for a total of 28,205 participants with MCI/dementia were included. In patients with MCI, mind-body intervention (standardized mean difference [SMD] = 0.36; 95% confidence intervals [CI] 0.20–0.52; low certainty) and mixed physical activity interventions (SMD = 0.30; 95% CI 0.11–0.49; moderate certainty) had a small effect on global cognition, whereas resistance training (SMD = 0.80; 95% CI 0.29–1.31; very low certainty) had a large effect on global cognition. In people affected by dementia, physical activity/exercise was effective in improving global cognition in Alzheimer disease (SMD = 1.10; 95% CI 0.65–1.64; very low certainty) and in all types of dementia (SMD = 0.48; 95% CI 0.22–0.74; low certainty). Finally, physical activity/exercise improved noncognitive outcomes in people with dementia including falls, and neuropsychiatric symptoms. Conclusions and Implications Supported by very low-to-moderate certainty of evidence, physical activity/exercise has a positive effect on several cognitive and noncognitive outcomes in people with MCI and dementia, but RCTs, with low risk of bias/confounding, are still needed to confirm these relationships.

Published
2020

97. The role of Apolipoprotein E epsilon4 in the association between psychosocial working conditions and dementia

Author

Pan, Kuan-Yu, Xu, Weili, Mangialasche, Francesca, Grande, Giulia, Fratiglioni, Laura, Wang, Hui-Xin, Psychiatry, and APH - Mental Health

Subjects
mental disorders
Abstract

In this population-based prospective study, we examined the association of job demand-control combinations with dementia, and explored the roles of Apolipoprotein E epsilon4 (APOE ɛ4) and work duration in this association. A total of 2,579 dementia-free individuals aged 60+ years from Sweden were followed over 12 years. Dementia diagnosis was made by physicians. Lifelong occupational experience was collected, and job demands and control were assessed using a psychosocial job-exposure matrix. Data were analyzed using multivariate Cox proportional hazard models. During the follow-up, 282 people developed dementia. Passive jobs (low control/low demands) were related to a higher risk of dementia compared with active jobs (high control/high demands) among the younger-old (aged ≤72 years), but not among the older-old (aged ≥78 years). Among the younger-old, compared to those with no passive job experience, those with 11+ years in passive jobs had a higher dementia risk. The joint-effect analyses showed that APOE ɛ4 carriers with passive jobs had an even higher risk of dementia compared to APOE ɛ4 non-carriers with active jobs. These findings suggest that passive jobs are related to a higher dementia risk among the younger-old. APOE ɛ4 and long work duration may amplify the impact of passive jobs on dementia.

Published
2020

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

Author

Grande, Giulia, Vetrano, Davide L., Mazzoleni, Francesco, Lovato, Valeria, Pata, Mario, Cricelli, Claudio, Lapi, Francesco, Grande, Giulia, Vetrano, Davide L., Mazzoleni, Francesco, Lovato, Valeria, Pata, Mario, Cricelli, Claudio, and Lapi, Francesco

Abstract

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 p

Published
2020
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99. The impact of delirium on outcomes for older adults hospitalised with COVID--19

Author

Marengoni, Alessandra, Zucchelli, Alberto, Grande, Giulia, Fratiglioni, Laura, Rizzuto, Debora, Marengoni, Alessandra, Zucchelli, Alberto, Grande, Giulia, Fratiglioni, Laura, and Rizzuto, Debora

Abstract

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.

Published
2020
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100. Tracing temporal trends in dementia incidence over 25 years in central Stockholm, Sweden

Author

Ding, Mozhu, Qiu, Chengxuan, Rizzuto, Debora, Grande, Giulia, Fratiglioni, Laura, Ding, Mozhu, Qiu, Chengxuan, Rizzuto, Debora, Grande, Giulia, and Fratiglioni, Laura

Abstract

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.

Published
2020
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