Smoking and Obesity as Risk Factors in Frontotemporal Dementia and Alzheimer’s Disease: The HUNT Study

Background: Few studies have assessed smoking and obesity together as risk factors for frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Objective: To study smoking and obesity as risk factors for FTD and AD. Methods: Ninety patients with FTD and 654 patients with AD were compared with 116 cognitively healthy elderly individuals in a longitudinal design with 15–31 years between measurements of risk factors before the dementia diagnosis. Results: There were no associations between smoking and FTD (p = 0.218; odds ratio [OR]: 0.990; 95% confidence interval [CI]: 0.975–1.006). There were significant associations between obesity and FTD (p = 0.049; OR: 2.629; 95% CI: 1.003–6.894). There were significant associations between both smoking (p = 0.014; OR: 0.987; 95% CI: 0.977–0.997) and obesity (p = 0.015; OR: 2.679; 95% CI: 1.211–5.928) and AD. Conclusion: Our findings suggest that obesity is a shared risk factor for FTD and AD, while smoking plays various roles as a risk factor for FTD and AD.

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Anxiety and Depression as Risk Factors in Frontotemporal Dementia and Alzheimer’s Disease: The HUNT Study

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000493973 ◽

2018 ◽

Vol 8 (3) ◽

pp. 414-425 ◽

Cited By ~ 2

Author(s):

Hege Rasmussen ◽

Tor Atle Rosness ◽

Ole Bosnes ◽

Øyvind Salvesen ◽

Marlen Knutli ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Depression Scale ◽

Health Study ◽

Anxiety And Depression ◽

Increased Risk ◽

Hunt Study ◽

Independent Risk Factors

Background: The roles of both anxiety and depression as risk factors for frontotemporal dementia (FTD) and Alzheimer’s disease (AD) have not been previously investigated together. Objective: To study anxiety and depression as independent risk factors for FTD and AD. Methods: Eighty-four patients with FTD and 556 patients with AD were compared with 117 cognitively healthy (CH), elderly individuals. Both cases and controls were participants in the second Health Study of Nord-Trøndelag (HUNT2) from 1995 to 1997, in which depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS). Results: Significant associations were found between anxiety and FTD and between depression and AD. A significantly increased risk of developing FTD was observed in patients who had reported anxiety on the HADS (p = 0.017) (odds ratio [OR]: 2.947, 95% confidence interval [CI]: 1.209–7.158) and a significantly increased risk of developing AD was observed in patients who had reported depression on the HADS (p = 0.016) (OR: 4.389, 95% CI: 1.311–14.690). Conclusion: Our study findings suggest that anxiety and depression may play different roles as risk factors for FTD and AD.

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Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2020-000759 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000759

Author(s):

Daniel Higbee ◽

Raquel Granell ◽

Esther Walton ◽

Roxanna Korologou-Linden ◽

George Davey Smith ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lung Function ◽

Causal Relationship ◽

Mendelian Randomisation ◽

P Value ◽

Unmeasured Confounding ◽

Increased Risk ◽

Shared Risk

RationaleLarge retrospective case-control studies have reported an association between chronic obstructive pulmonary disease (COPD), reduced lung function and an increased risk of Alzheimer’s disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors. Conventional observational epidemiology suffers from unmeasured confounding and reverse causation. Additional analyses addressing causality are required.ObjectivesTo examine a causal relationship between COPD, lung function and Alzheimer’s disease.MethodsUsing two-sample Mendelian randomisation, we used single nucleotide polymorphisms (SNPs) identified in a genome wide association study (GWAS) for lung function as instrumental variables (exposure). Additionally, we used SNPs discovered in a GWAS for COPD in those with moderate to very severe obstruction. The effect of these SNPs on Alzheimer’s disease (outcome) was taken from a GWAS based on a sample of 24 807 patients and 55 058 controls.ResultsWe found minimal evidence for an effect of either lung function (OR: 1.02 per SD; 95% CI 0.91 to 1.13; p value 0.68) or liability for COPD on Alzheimer’s disease (OR: 0.97 per SD; 95% CI 0.92 to 1.03; p value 0.40).ConclusionNeither reduced lung function nor liability COPD are likely to be causally associated with an increased risk of Alzheimer’s, any observed association is likely due to unmeasured confounding. Scientific attention and health prevention policy may be better focused on overlapping risk factors, rather than attempts to reduce risk of Alzheimer’s disease by targeting impaired lung function or COPD directly.

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Vascular and mixed dementias

10.1093/med/9780199644957.003.0034 ◽

2013 ◽

Cited By ~ 1

Author(s):

Robert Stewart

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Controlled Trial ◽

Diagnostic System ◽

Research Area ◽

Risk Factor Control ◽

Randomised Controlled ◽

Trial Evidence

Vascular disease is the most important environmental risk factor for dementia but this research area has been hampered by inadequate outcome definitions – in particular, a diagnostic system that attempts to separate overlapping and probably interacting pathologies. There is now substantial evidence that the well-recognised risk factors for cardiovascular disease and stroke are also risk factors for dementia, including Alzheimer’s disease. However, these risk factors frequently act over several decades, meaning that the chances of definitive randomised controlled trial evidence for risk-modifying interventions are slim. This should not obscure the wide opportunity for delaying or preventing dementia through risk factor control and uncontroversial healthy lifestyles. Care should also be taken that comorbid cerebrovascular disease is not considered as excluding a diagnosis of Alzheimer’s disease, particularly now that this determines treatment eligibility.

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Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2013.08.011 ◽

2014 ◽

Vol 35 (2) ◽

pp. 444.e1-444.e4 ◽

Cited By ~ 66

Author(s):

Agustín Ruiz ◽

Oriol Dols-Icardo ◽

María J. Bullido ◽

Pau Pastor ◽

Eloy Rodríguez-Rodríguez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Frontotemporal Dementia

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P1-105: Behavioral variant of Alzheimer's disease in an old woman mimicking frontotemporal dementia: Diagnosis contribution of CSF biomarkers

Alzheimer s & Dementia ◽

10.1016/j.jalz.2011.05.384 ◽

2011 ◽

Vol 7 ◽

pp. S143-S144

Author(s):

Pauline Lapalus ◽

Claire Paquet ◽

Jacques Hugon ◽

Julien Dumurgier ◽

Jean Pierre Guichard ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Csf Biomarkers ◽

Dementia Diagnosis

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Risk factors and global cognitive status related to brain arteriolosclerosis in elderly individuals

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15621574 ◽

2016 ◽

Vol 37 (1) ◽

pp. 201-216 ◽

Cited By ~ 32

Author(s):

Eseosa T Ighodaro ◽

Erin L Abner ◽

David W Fardo ◽

Ai-Ling Lin ◽

Yuriko Katsumata ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Flow ◽

Risk Factor ◽

Cerebral Blood Flow ◽

Cognitive Status ◽

Data Set ◽

Convenience Sample ◽

Risk Genotype

Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative data sets. Previous studies showed evidence of distinct neurodegenerative disease outcomes and clinical-pathological correlations in the “oldest-old” compared to younger cohorts. Therefore, using the National Alzheimer's Coordinating Center data set, we analyzed clinical and neuropathological data from two groups according to ages at death: < 80 years ( n = 1008) and ≥80 years ( n = 1382). In both age groups, severe brain arteriolosclerosis was associated with worse performances on global cognition tests. Hypertension (but not diabetes) was a brain arteriolosclerosis risk factor in the younger group. In the ≥ 80 years age at death group, an ABCC9 gene variant (rs704180), previously associated with aging-related hippocampal sclerosis, was also associated with brain arteriolosclerosis. A post-hoc arterial spin labeling neuroimaging experiment indicated that ABCC9 genotype is associated with cerebral blood flow impairment; in a convenience sample from Alzheimer's Disease Neuroimaging Initiative ( n = 15, homozygous individuals), non-risk genotype carriers showed higher global cerebral blood flow compared to risk genotype carriers. We conclude that brain arteriolosclerosis is associated with altered cognitive status and a novel vascular genetic risk factor.

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OVERSIMPLIFICATION OF DEMENTIA RISK REDUCTION MESSAGING IS A THREAT TO KNOWLEDGE TRANSLATION IN DEMENTIA PREVENTION RESEARCH

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2017.27 ◽

2017 ◽

pp. 1-3

Author(s):

K.J. Anstey ◽

R. Peters

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Knowledge Translation ◽

Risk Reduction ◽

Assessment Tools ◽

Prevention Research ◽

Dementia Risk ◽

Dementia Prevention

The evidence for specific risk factors for Alzheimer’s disease, vascular dementia and all cause dementia is increasing rapidly in quantity and quality. This has enabled the compilation of risk assessment tools for Alzheimer’s disease (1), and their validation (2). It has also supported the promulgation of public health messaging about dementia risk reduction or dementia prevention. In general these developments are strong advances in the field of dementia prevention. However, the oversimplification of the findings and possible over-or mis-interpretation of their meaning, poses risks to accurate and effective knowledge translation in this field. Lack of balance in the interpretation of evidence on risk factors for dementia may lead to trials of interventions for dementia prevention that are ineffective. This will waste resources and create pessimism about dementia prevention research. Two potential problems that may occur when translating evidence from observational research into prescriptions for prevention are identified here. The first is the generalisation of specific findings about risk factors either to multiple types of dementia or to multiple populations, when the evidence is in fact relevant to specific populations or outcomes. The second is the inference that reversal of a risk factor will lead to prevention, without knowledge of the threshold at which a factor becomes a ‘risk’, or evidence that reversal of the risk factor also reverses neuropathological processes instigated or caused by the risk factor.

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Awareness of putative risk factors for Alzheimer’s disease among elderly Koreans

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2007.00230.x ◽

2008 ◽

Vol 20 (1) ◽

pp. 20-24 ◽

Cited By ~ 4

Author(s):

Moon Ho Park ◽

Sangmee Ahn Jo ◽

Inho Jo ◽

Eunkyung Kim ◽

Eun Kyung Woo ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Economic Status ◽

Public Health Education ◽

Level Of Education ◽

Sociodemographic Data ◽

Older Subjects ◽

Elderly Koreans

Objective:Although there are rapidly growing concerns about the high rates of cognitive dysfunction in Korea, the knowledge of risk factors for Alzheimer’s disease (AD) among the general public in Korea remains to be elucidated.Methods:A total of 2767 randomly selected subjects from the Ansan Geriatric Study were questioned on their knowledge of putative risk factors for AD. Their answers were compared with their sociodemographic data and other variables.Results:The most common stated risk factor was being older (59.6%), followed by head trauma (33.6%) and cerebrovascular disease (30.4%). However, a substandard education, which is a known risk factor, was considered significant by only 9.5% of the subjects. Predictors for a worse knowledge of the risk factors for AD were being older, a lower level of education, lower economic status and the attitude that dementia is not curable.Conclusion:This study revealed that misunderstanding about AD is more prevalent in older subjects and those with a lower level of education, and so public health education on the basic concepts of AD should be targeted at this population.

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Vascular risk burden is a key player in the early progression of Alzheimer's disease

10.1101/2021.12.18.21267994 ◽

2021 ◽

Author(s):

João Pedro Ferrari-Souza ◽

Wagner S. Brum ◽

Lucas A. Hauschild ◽

Lucas U. Da Ros ◽

Pâmela C. L. Ferreira ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Cognitive Decline ◽

Vascular Risk Factor ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Preclinical Alzheimer’S Disease ◽

Risk Factor Burden

Understanding whether vascular risk factors synergistically potentiate Alzheimer's disease progression is important in the context of emerging treatments for preclinical Alzheimer's disease. The existence of a synergistic relationship could suggest that the combination of therapies targeting Alzheimer's disease pathophysiology and vascular risk factors might potentiate treatment outcomes. In the present retrospective cohort study, we tested whether vascular risk factor burden interacts with Alzheimer's disease pathophysiology to accelerate neurodegeneration and cognitive decline in cognitively unimpaired subjects. We evaluated 503 cognitively unimpaired participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Baseline vascular risk factor burden was calculated considering the history of cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, stroke or transient ischemic attack, smoking, atrial fibrillation, and left ventricular hypertrophy. Alzheimer's disease pathophysiology was evaluated using cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ1-42) reflecting brain amyloidosis (A) and tau phosphorylated at threonine 181 (p-tau181) reflecting brain tau pathology (T). Individuals were dichotomized as having an elevated vascular risk factor burden (V+ if having two or more vascular risk factors) and as presenting preclinical Alzheimer's disease [(AT)+ if having abnormal CSF p-tau181 and Aβ1-42 levels]. Neurodegeneration was assessed with plasma neurofilament light (NfL) and global cognition with the modified version of the Preclinical Alzheimer's Cognitive Composite. Linear mixed-effects models revealed that an elevated vascular risk factor burden synergistically interacted with Alzheimer's disease pathophysiology to drive longitudinal increases in plasma NfL levels (β = 5.08, P = 0.016) and cognitive decline (β = -0.43, P = 0.020). Additionally, we observed that vascular risk factor burden was not associated with CSF Aβ1-42 or p-tau181 changes over time. Survival analysis demonstrated that individuals with preclinical Alzheimer's disease and elevated vascular risk factor burden [(AT)+V+] had a significantly greater risk of clinical progression to cognitive impairment (adjusted Hazard Ratio = 3.5, P < 0.001). Our results support the notion that vascular risk factor burden and Alzheimer's disease pathophysiology are independent processes; however, they synergistically lead to neurodegeneration and cognitive decline. These findings can help in providing the blueprints for the combination of vascular risk factor management and Alzheimer's disease pathophysiology treatment in preclinical stages. Moreover, we observed plasma NfL as a robust marker of disease progression that may be used to track therapeutic response in future trials.

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Can SARS-CoV-2 Infection Exacerbate Alzheimer’s Disease? An Overview of Shared Risk Factors and Pathogenetic Mechanisms

Journal of Personalized Medicine ◽

10.3390/jpm12010029 ◽

2022 ◽

Vol 12 (1) ◽

pp. 29

Author(s):

Chiara Villa ◽

Eleonora Rivellini ◽

Marialuisa Lavitrano ◽

Romina Combi

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Public Healthcare ◽

Vulnerable Group ◽

Pathogenetic Mechanisms ◽

Care Access ◽

The Central Nervous System ◽

Common Risk Factors ◽

Shared Risk

The current coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, is affecting every aspect of global society, including public healthcare systems, medical care access, and the economy. Although the respiratory tract is primarily affected by SARS-CoV-2, emerging evidence suggests that the virus may also reach the central nervous system (CNS), leading to several neurological issues. In particular, people with a diagnosis of Alzheimer’s disease (AD) are a vulnerable group at high risk of contracting COVID-19, and develop more severe forms and worse outcomes, including death. Therefore, understanding shared links between COVID-19 and AD could aid the development of therapeutic strategies against both. Herein, we reviewed common risk factors and potential pathogenetic mechanisms that might contribute to the acceleration of neurodegenerative processes in AD patients infected by SARS-CoV-2.

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