Vascular and mixed dementia

2020 ◽  
pp. 479-494
Author(s):  
Robert Stewart
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Controlled Trial ◽  
Diagnostic System ◽  
Research Area ◽  
Healthy Lifestyles ◽  
Environmental Risk Factor ◽  
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-recognized 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 randomized 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.

Vascular and mixed dementias

2013 ◽  
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.

scholarly journals Dysregulation of Hypothalamic-Pituitary-Adrenal (HPA) Axis in Alzheimer’s Disease and use of Non Selective and Selective Glucocorticoid Receptor Modulators to Improve Cognitive function – Review of Literature

2017 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Hpa Axis ◽  
Memory Loss ◽  
Environmental Risk Factor ◽  
Review Of Literature ◽  
Hypothalamic Pituitary Adrenal ◽  
Potential Therapeutic Role ◽  
Receptor Modulators

Alzheimer's disease (AD) is a relentless neurodegenerative disease affecting more than 36 million people worldwide. Increased evidence suggests stress and its synonymous elevated circulating glucocorticoid levels, due to dysregulation of Hypothalamic-Pituitary-Adrenal (HPA) axis, is an important environmental risk factor for the onset and progression of AD [1]. Here we review recent data on the effect of glucocorticoids on spontaneous activity of HPA axis with particular emphasis on AD, and how modulation of glucocorticoid (GC) levels or GC receptors (GCRs) could potentially mediate disease processes. Early phase of AD is characterized by hippocampal memory (episodic memory) loss and impaired synaptic plasticity [2]. In a study at IPMC in France on mouse model AD, treatment with GCR antagonist, mifepristone (RU486) reduced cerebral B Amyloid (AB), Tau pathologies and cognitive impairment [3]. Pointing to a potential therapeutic role for interventions to underlying HPA axis and GCRs activity.

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

2016 ◽  
Vol 37 (1) ◽  
pp. 201-216 ◽  
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.

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

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.

scholarly journals Hormonal treatment, mild cognitive impairment and Alzheimer's disease

2008 ◽  
Vol 20 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Joanne Ryan ◽  
Jaqueline Scali ◽  
Isabelle Carriere ◽  
Karen Ritchie ◽  
Marie-Laure Ancelin
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Verbal Memory ◽  
Late Onset ◽  
Controlled Trial ◽  
Hormonal Changes

ABSTRACTA plethora of in vitro and in vivo studies have supported the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy (HRT) trials in non-demented postmenopausal women suggest a temporary positive effect (notably on verbal memory), and four meta-analyses converge to suggest a possible protective effect in relation to Alzheimer's disease (reducing risk by 29 to 44%). However, data from the only large randomized controlled trial published to date, the Women's Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using HRT compared to controls. Apart from methodological differences, one key shortcoming of this trial has probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at a time when the neurodegenerative process has already begun and without taking into account individual lifetime exposure to hormone variability. Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia.

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

2008 ◽  
Vol 20 (1) ◽  
pp. 20-24 ◽  
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.

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

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.

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

2019 ◽  
Vol 9 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Hege Rasmussen Eid ◽  
Tor Atle Rosness ◽  
Ole Bosnes ◽  
Øyvind Salvesen ◽  
Marlen Knutli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Frontotemporal Dementia ◽  
Longitudinal Design ◽  
Dementia Diagnosis ◽  
Healthy Elderly ◽  
Hunt Study ◽  
Shared Risk

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.

scholarly journals Is Female Gender a Risk Factor for Alzheimer's Disease?

1999 ◽  
Vol 11 (3) ◽  
pp. 219-222 ◽  
Author(s):  
Gregory Swanwick ◽  
Brian A. Lawlor
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Gender Difference ◽  
Female Gender ◽  
Prevalence Rates ◽  
Survival Times ◽  
Gender Differential ◽  
Crude Prevalence

Despite a growing list of potential new risk factors for Alzheimer's disease (AD), one of the oldest remains controversial. Is female gender a risk factor for AD? It is likely that the greatest influence on the gender differential in crude prevalence rates is the increasing incidence of dementia with age (Paykel et al., 1994) combined with the greater longevity women (Moritz & Ostfeld, 1990). This must be distinguished from the hypothesis that there may also be a gender difference in the age-specific prevalence rates some dementias such as AD. In turn, this could be due to either a higher incidence dementia in women, or to longer survival times in women following diagnosis. What is the evidence for these hypotheses?

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