The journals of gerontology. Series A, Biological sciences and medical sciences, 2024

Longitudinal patterns of systolic blood pressure, diastolic blood pressure, cardiorespiratory fitness, and their association with dementia risk: The HUNT study

Abstract

Abstract

Background: High blood pressure and poor cardiorespiratory fitness are independent risk factors for dementia. However, few studies have examined if combined longitudinal patterns of these modifiable risk factors are associated with dementia risk.

Methods: In this prospective cohort study, we used data from the population-based HUNT Study, Norway. We applied group-based multidimensional trajectory modeling to identify age-specific multidimensional trajectories of SBP, DBP and estimated cardiorespiratory fitness across three surveys (HUNT1, 1984-86 – HUNT3, 2006-08). Dementia was diagnosed in the HUNT4 70+ substudy in 2017-19. We used multivariate logistic regression to estimate odds ratios (ORs) and risk differences (RDs) of dementia.

Results: In total, 7594 participants (54.9% women) were included, with a mean age of 44.7 (SD 6.3) years at HUNT1. Dementia was diagnosed in 1062 (14.0%) participants. We identified two multidimensional trajectories throughout adulthood within three age groups: one with higher SBP and DBP, and lower estimated cardiorespiratory fitness (the poorer group), and one with lower SBP and DBP, and higher cardiorespiratory fitness (the better group). After adjustment for sex, APOE ε4 status, education, marital status and diabetes, the better group had consistently lower risk of dementia in all age groups with the lowest OR in the middle-aged group of 0.63 (95% CI 0.51, 0.78) with corresponding RD of -0.07 (95% CI -0.10, -0.04).

Conclusions: Having a beneficial multidimensional trajectory of SBP, DBP and cardiorespiratory fitness in adulthood was associated with reduced dementia risk. Aiming for optimal SBP, DBP and estimated cardiorespiratory fitness throughout adulthood may reduce dementia risk.

Forfattere

Maren Lerfald, Heather Allore, Tom I L Nilsen, Rannveig S Eldholm, Nicolas Martinez-Velilla, Geir Selbæk & Linda Ernstsen

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Alzheimer's & Dementia, 2024

Genetic associations with psychosis and affective disturbance in Alzheimer’s disease

Abstract

Introduction: Individuals with Alzheimer’s disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study’s goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes.
Methods:
Genome-wide associationmeta-analysis of 9988 AD participants from six source studies with participants characterized for AD+PAD+A, and a joint phenotype (AD+A+P).
Results:
AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms.AD+Awas positively correlatedwith anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereasAD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations.
Discussion:
AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development.

Forfattere

Inga Margret Antonsdottir, Byron Creese, Lambertus Klei, Mary Ann A. DeMichele-Sweet, Elise A. Weamer, Pablo Garcia-Gonzalez, Marta Marquie, Mercè Boada, Emilio Alarcón-Martín,  Sergi Valero, NIA-LOAD Family Based Study Consortium, Alzheimer’s Disease Genetics Consortium (ADGC), AddNeuroMed Consortium, Yushi Liu, Basavaraj Hooli, Dag Aarsland, Geir Selbaek, Sverre Bergh, Arvid Rongve, Ingvild Saltvedt, Håvard K. Skjellegrind, Bo Engdahl, Ole A. Andreassen, Barbara Borroni, Patrizia Mecocci, Yehani Wedatilake, Richard Mayeux, Tatiana Foroud, Agustín Ruiz, Oscar L. Lopez, M. Ilyas Kamboh, Clive Ballard, Bernie Devlin, Constantine Lyketsos & Robert A. Sweet

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