scholarly journals Antiherpetic drugs: a potential way to prevent Alzheimer’s disease?

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Morgane Linard ◽  
Julien Bezin ◽  
Emilie Hucteau ◽  
Pierre Joly ◽  
Isabelle Garrigue ◽  
...  

Abstract Background Considering the growing body of evidence suggesting a potential implication of herpesviruses in the development of dementia, several authors have questioned a protective effect of antiherpetic drugs (AHDs) which may represent a new means of prevention, well tolerated and easily accessible. Subsequently, several epidemiological studies have shown a reduction in the risk of dementia in subjects treated with AHDs, but the biological plausibility of this association and the impact of potential methodological biases need to be discussed in more depth. Methods Using a French medico-administrative database, we assessed the association between the intake of systemic AHDs and the incidence of (i) dementia, (ii) Alzheimer’s disease (AD), and (iii) vascular dementia in 68,291 subjects over 65 who were followed between 2009 and 2017. Regarding potential methodological biases, Cox models were adjusted for numerous potential confounding factors (including proxies of sociodemographic status, comorbidities, and use of healthcare) and sensitivity analyses were performed in an attempt to limit the risk of indication and reverse causality biases. Results 9.7% of subjects (n=6642) had at least one intake of systemic AHD, and 8883 incident cases of dementia were identified. Intake of at least one systemic AHD during follow-up was significantly associated with a decreased risk of AD (aHR 0.85 95% confidence interval [0.75–0.96], p=0.009) and, to a lesser extent with respect to p values, to both dementia from any cause and vascular dementia. The association with AD remained significant in sensitivity analyses. The number of subjects with a regular intake was low and prevented us from studying its association with dementia. Conclusions Taking at least one systemic AHD during follow-up was significantly associated with a 15% reduced risk of developing AD, even after taking into account several potential methodological biases. Nevertheless, the low frequency of subjects with a regular intake questions the biological plausibility of this association and highlights the limits of epidemiological data to evaluate a potential protective effect of a regular treatment by systemic AHDs on the incidence of dementia

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Oskar Hansson ◽  
Martina Svensson ◽  
Anna-Märta Gustavsson ◽  
Emelie Andersson ◽  
Yiyi Yang ◽  
...  

Abstract Background Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer’s disease (AD) differently in two large study populations with different designs. Methods Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5–15 years). Next, we studied the association between self-reported physical activity, stated twice 5 years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18 years of follow-up (median 15, IQR 14–17 years). Finally, we used a mouse model of AD and studied brain levels of amyloid-β, synaptic proteins, and cognitive function following 6 months of voluntary wheel running. Results Vasaloppet skiers (median age 36.0 years [IQR 29.0–46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52–0.75) and VaD (adjusted HR 0.49, 95% CI 0.33–0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16–0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5 years [IQR 51.0–63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent of APOE-ε4 genotype. In AD mice, voluntary running did not improve memory, amyloid-β, or synaptic proteins. Conclusions Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.


2020 ◽  
pp. 1-13
Author(s):  
Karolina Minta ◽  
Gunnar Brinkmalm ◽  
Erik Portelius ◽  
Per Johansson ◽  
Johan Svensson ◽  
...  

Background: Brevican and neurocan are central nervous system-specific extracellular matrix proteoglycans. They are degraded by extracellular enzymes, such as metalloproteinases. However, their degradation profile is largely unexplored in cerebrospinal fluid (CSF). Objective: The study aim was to quantify proteolytic peptides derived from brevican and neurocan in human CSF of patients with Alzheimer’s disease (AD) and vascular dementia (VaD) compared with controls. Methods: The first cohort consisted of 75 individuals including 25 patients with AD, 7 with mild cognitive impairment (MCI) diagnosed with AD upon follow-up, 10 patients with VaD or MCI diagnosed with VaD upon follow-up, and 33 healthy controls and cognitively stable MCI patients. In the second cohort, 31 individuals were included (5 AD patients, 14 VaD patients and 12 healthy controls). Twenty proteolytic peptides derived from brevican (n = 9) and neurocan (n = 11) were quantified using high-resolution parallel reaction monitoring mass spectrometry. Results: In the first cohort, the majority of CSF concentrations of brevican and neurocan peptides were significantly decreased inVaDas compared withADpatients (AUC = 0.83.0.93, p≤0.05) and as compared with the control group (AUC = 0.79.0.87, p ≤ 0.05). In the second cohort, CSF concentrations of two brevican peptides (B87, B156) were significantly decreased in VaD compared with AD (AUC = 0.86.0.91, p ≤ 0.05) and to controls (AUC = 0.80.0.82, p ≤ 0.05), while other brevican and neurocan peptides showed a clear trend to be decreased in VaD compared with AD (AUC = 0.64.80, p > 0.05). No peptides differed between AD and controls. Conclusion: Brevican and neurocan peptides are potential diagnostic biomarkers for VaD, with ability to separate VaD from AD.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Chris B. Guure ◽  
Noor A. Ibrahim ◽  
Mohd B. Adam ◽  
Salmiah Md Said

The association of physical activity with dementia and its subtypes has remained controversial in the literature and has continued to be a subject of debate among researchers. A systematic review and meta-analysis of longitudinal studies on the relationship between physical activity and the risk of cognitive decline, all-cause dementia, Alzheimer’s disease, and vascular dementia among nondemented subjects are considered. A comprehensive literature search in all available databases was conducted up until April 2016. Well-defined inclusion and exclusion criteria were developed with focus on prospective studies ≥ 12 months. The overall sample from all studies is 117410 with the highest follow-up of 28 years. The analyses are performed with both Bayesian parametric and nonparametric models. Our analysis reveals a protective effect for high physical activity on all-cause dementia, odds ratio of 0.79, 95% CI (0.69, 0.88), a higher and better protective effect for Alzheimer’s disease, odds ratio of 0.62, 95% CI (0.49, 0.75), cognitive decline odds ratio of 0.67, 95% CI (0.55, 0.78), and a nonprotective effect for vascular dementia of 0.92, 95% CI (0.62, 1.30). Our findings suggest that physical activity is more protective against Alzheimer’s disease than it is for all-cause dementia, vascular dementia, and cognitive decline.


2018 ◽  
Vol 33 (6) ◽  
pp. 385-393 ◽  
Author(s):  
Jakub Kazmierski ◽  
Chaido Messini-Zachou ◽  
Mara Gkioka ◽  
Magda Tsolaki

Cholinesterase inhibitors (ChEIs) are the mainstays of symptomatic treatment of Alzheimer’s disease (AD); however, their efficacy is limited, and their use was associated with deaths in some groups of patients. The aim of the current study was to assess the impact of the long-term use of ChEIs on mortality in patients with AD. This observational, longitudinal study included 1171 adult patients with a diagnosis of AD treated with donepezil or rivastigmine. Each patient was observed for 24 months or until death. The cognitive and functional assessments, the use of ChEIs, memantine, antipsychotics, antidepressants, and anxiolytics were recorded. The total number of deaths at the end of the observational period was 99 (8.45%). The patients who had received rivastigmine treatment were at an increased risk of death in the follow-up period. The higher risk of death in the rivastigmine group remained significant in multivariate Cox regression models.


2018 ◽  
Vol 213 (5) ◽  
pp. 654-660 ◽  
Author(s):  
Eva Becker ◽  
Claudia Lorena Orellana Rios ◽  
Claas Lahmann ◽  
Gerta Rücker ◽  
Joachim Bauer ◽  
...  

BackgroundThe aetiology of dementia is not yet fully understood. Stress can have a damaging effect on brain health. The prognostic effect of anxiety is still unclear regarding Alzheimer's disease as well as vascular dementia.AimsTo explore the association between anxiety and future dementia.MethodMedline, PsycINFO, CINAHL, Web of Science and ALOIS were searched for publications up to 12 January 2018. Longitudinal studies with a follow-up of at least 2 years were included, if the trait or state anxiety had been assessed at baseline. Studies with cognitive impairment at baseline were not included. We used a random effects model to calculate the pooled time to Alzheimer's disease and incidence of vascular dementia.ResultsAnxiety predicts risk of Alzheimer's disease (n = 26 193 out of seven studies, hazard ratio1.53, 95% CI 1.16–2.01, P < 0.01) and vascular dementia (n = 4916 out of two studies, odds ratio1.88, 95% CI 1.05–3.36, P < 0.01). The pooled hazard ratio regarding risk of Alzheimer's disease was still significant when excluding studies with critical risk of bias (n = 14 110 out of six studies, hazard ratio 1.35, 95% CI 1.08–1.70, P < 0.01).ConclusionsAnxiety is a risk factor for both types of dementia. The temporal and functional relation between anxiety and dementia needs investigation in future studies. The protective value of treating anxiety should be explored further.Declaration of interestNone.


2012 ◽  
Vol 25 (1) ◽  
pp. 167-168 ◽  
Author(s):  
Christine E. Gould ◽  
Sherry A. Beaudreau ◽  
Huma Salman

Individuals with diabetes mellitus have a 1.39 times increased risk of Alzheimer's disease, a 2.38 times increased risk of vascular dementia, and a faster rate of cognitive decline compared to individuals without diabetes (Lu et al., 2009). In a study, over a 9-year follow-up diabetes was associated with accelerated progression from mild cognitive impairment (MCI) to dementia, but was not associated with progression from no impairment to MCI (Xu et al., 2010). Many previous studies on cognitive impairment and diabetes are limited by the use of cognitive screens to diagnose and assess cognitive impairment. A few studies diagnosing cognitive impairment with comprehensive neuropsychological batteries provide mixed results. For instance, Luchinger et al. (2007) found that diabetes was correlated with the presence of MCI, whereas diabetes was not associated with the presence of dementia versus no dementia in the Aging, Demographics, and Memory Study ADAMS; (Llewellyn et al., 2010).


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Norio Sugawara ◽  
Norio Yasui-Furukori ◽  
Kazutaka Shimoda

Abstract Background Depopulation accompanied by population aging is a major public health concern in Japan. Although adequate allocation of mental healthcare resources is needed, there have been few studies on the impact of population change on the supply–demand balance for mental illness in Japan. The aim of this study is to predict psychiatrists' distribution for patients with mental illness via a utilization-based approach. Methods We set patients with schizophrenia, mood disorders, vascular dementia or Alzheimer’s disease as study subjects and conducted analyses for 2015, 2025, 2035, and 2045 across all prefectures. Moreover, we evaluated the regional maldistribution of demand and supply by calculating the number of psychiatrists per patient, Gini coefficients (GC), and Herfindahl–Hirschman Index (HHI). Results The mean number of psychiatrists per patient for patients with schizophrenia, mood disorders, vascular dementia, and Alzheimer’s disease in 2025, 2035, and 2045 was significantly lower than in 2015. For all of the abovementioned diseases, both the GC and HHI will increase until 2045. Conclusion If psychiatrists are allocated at the current population-to-psychiatrist ratio, the shortage of psychiatrists will continue to worsen in the future. To overcome this inequity, policy makers should make plans to shift responsibilities from psychiatrists to other mental health workers and to ensure the adequate geographical allocation of healthcare resources.


2018 ◽  
Vol 30 (7) ◽  
pp. 947-956 ◽  
Author(s):  
Aleksi Hamina ◽  
Piia Lavikainen ◽  
Antti Tanskanen ◽  
Anna-Maija Tolppanen ◽  
Jari Tiihonen ◽  
...  

ABSTRACTBackground:We analyzed the impact of opioid initiation on the prevalence of antipsychotic and benzodiazepine and related drug (BZDR) use among community-dwelling persons with Alzheimer's disease (AD).Methods:We utilized the register-based Medication use and Alzheimer's disease (MEDALZ) cohort for this study. We included all community-dwelling persons diagnosed with AD during 2010–2011 in Finland initiating opioid use (n = 3,327) and a matched cohort of persons not initiating opioids (n = 3,325). Interrupted time series analyses were conducted to compare the prevalence of antipsychotic and BZDR use in 30-day periods within six months before opioid initiation to 30-day periods six months later.Results:Before opioid initiation, prevalence of antipsychotic use among opioid initiators was 13.3%, 18.3% at opioid initiation, and 17.3% six months later. Prevalences of BZDR use were 27.1% six months prior, 28.9% at opioid initiation, and 26.9% six months later. After opioid initiation, antipsychotic and BZDR use declined by 0.3 percentage points (pps, 95% confidence interval 0.1–0.5) and 0.4 pps (0.2–0.7) per month, respectively, until the end of the follow-up. Compared to persons not initiating opioid use, opioid initiation immediately resulted in an increase in prevalence of 1.9 pps (0.9–2.8) for antipsychotics and of 1.6 pps (0.9–2.2) for BZDR use. However, in total there was a comparative decrease of 0.5 pps (0.3–0.8) per month for antipsychotics and of 0.4 pps (0.2–0.6) for BZDR use until the end of the follow-up.Conclusion:Our results suggest that opioid initiation may reduce antipsychotic and BZDR use among persons with AD.


2012 ◽  
Vol 18 (5) ◽  
pp. 372-380 ◽  
Author(s):  
Hugh Series ◽  
Margaret Esiri

SummaryVascular dementia is associated with a group of diverse pathologies affecting the cerebrovascular circulation and with other dementia pathologies, particularly Alzheimer's disease. It is rather rare on its own. There is a spectrum of severity of cerebrovascular disease ranging from pathology but no cognitive impairment, to mild cognitive impairment to a dementia syndrome (vascular dementia). Where present, cerebrovascular disease can magnify the impact of other pathologies such as Alzheimer's disease. Current criteria for diagnosing vascular dementia are inadequate. Neuroimaging can be very helpful in defining the extent of pathology. Assessment needs to take into account a wide range of issues. Specific evidence-based treatments are limited, but attention should be given to managing risk factors and associated psychiatric problems such as depression.


Author(s):  
Weiyao Yin ◽  
Marie Löf ◽  
Ruoqing Chen ◽  
Christina M. Hultman ◽  
Fang Fang ◽  
...  

Abstract Background Depression imposes immense public health burden, demonstrating an urgent need of the identification of modifiable risk factors. Only a few cohort studies have analyzed the association between Mediterranean dietary pattern (MDP) and depression but with mixed results. We examined the impact of MDP on clinically ascertained depression in a large population-based dataset. Methods In 1991/92, detailed information on diet, using a food frequency questionnaire, and potential confounding factors (body weight, height, educational attainment, smoking, previous diabetes and hypertension, and physical activity) was collected, in a random sample of 49,261 Swedish women aged 29-49. Adherence to MDP was calculated. Clinical depression was extracted from the National Patient Register. Study participants were followed up through 2012. Results During an average follow-up of 20.4 years, 1677 incident cases of depression were diagnosed. We observed a lower risk of depression for medium (score 4-5) and high (6-9) adherence to MDP, compared with low (0-3) adherence (Medium: hazard ratio (HR) = 0.90, 95% confidence interval (CI) = 0.81-1.00; High: HR = 0.82, 95%CI = 0.71-0.94). Per unit increase of adherence, the risk of depression was reduced by 5% (HR = 0.95, 95%CI = 0.92-0.98). The association became stronger when restricting to severe form of depression (HR = 0.51, 95%CI = 0.33-0.76). The HRs were higher from age 50 onward both over the first and the second 10-year follow-up period, compared with before age 50, indicating stronger association with increasing age. Results remained after extensive sensitivity analyses. Conclusion Higher adherence to a Mediterranean diet at middle age was associated with a lower risk of depression later in life among Swedish women.


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