Alzheimer's disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual's sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology.
- MeSH
- Alzheimer Disease * diagnosis epidemiology MeSH
- Amyloid beta-Peptides MeSH
- Biomarkers MeSH
- Clinical Trials as Topic MeSH
- Cognition * MeSH
- Cognition Disorders * MeSH
- Humans MeSH
- Neurology MeSH
- Sex Characteristics MeSH
- tau Proteins MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: The association between mortality risk and use of antidepressants in people with dementia is unknown. OBJECTIVE: To describe the use of antidepressants in people with different dementia diagnoses and to explore mortality risk associated with use of antidepressants 3 years before a dementia diagnosis. METHODS: Study population included 20 050 memory clinic patients from the Swedish Dementia Registry (SveDem) diagnosed with incident dementia. Data on antidepressants dispensed at the time of dementia diagnosis and during 3-year period before dementia diagnosis were obtained from the Swedish Prescribed Drug Register. Cox regression models were used. RESULTS: During a median follow-up of 2 years from dementia diagnosis, 25.8% of dementia patients died. A quarter (25.0%) of patients were on antidepressants at the time of dementia diagnosis, while 21.6% used antidepressants at some point during a 3-year period before a dementia diagnosis. Use of antidepressant treatment for 3 consecutive years before a dementia diagnosis was associated with a lower mortality risk for all dementia disorders and in Alzheimer's disease. CONCLUSION: Antidepressant treatment is common among patients with dementia. Use of antidepressants during prodromal stages may reduce mortality in dementia and specifically in Alzheimer's disease.
- MeSH
- Antidepressive Agents therapeutic use MeSH
- Dementia diagnosis drug therapy mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Prospective Studies MeSH
- Registries MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Sweden epidemiology MeSH
It has recently been proposed that heart failure is a risk factor for Alzheimer's disease. Decreased cerebral blood flow and neurohormonal activation due to heart failure may contribute to the dysfunction of the neurovascular unit and cause an energy crisis in neurons. This leads to the impaired clearance of amyloid beta and hyperphosphorylation of tau protein, resulting in the formation of amyloid beta plaques and neurofibrillary tangles. In this article, we will summarize the current understanding of the relationship between heart failure and Alzheimer's disease based on epidemiological studies, brain imaging research, pathological findings and the use of animal models. The importance of atherosclerosis, myocardial infarction, atrial fibrillation, blood pressure and valve disease as well as the effect of relevant medications will be discussed.
- MeSH
- Alzheimer Disease epidemiology MeSH
- Atrial Fibrillation epidemiology MeSH
- Hypertension physiopathology MeSH
- Myocardial Infarction epidemiology MeSH
- Intracranial Arteriosclerosis epidemiology MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Cerebrovascular Circulation MeSH
- Risk Factors MeSH
- Heart Failure epidemiology physiopathology MeSH
- Sleep Apnea Syndromes epidemiology MeSH
- Stroke Volume MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
This review comprehensively examines the current knowledge on the relationship between body mass index (BMI) and dementia. The association between BMI and cognition is complex: in younger adults, higher BMIs are associated with impaired cognition. Overweight and obesity in middle age are linked to increased future dementia risk in old age. However, when examined in old age, higher BMIs are associated with better cognition and decreased mortality. Little is known about the optimal BMI for well-being and survival in populations already suffering from dementia. Lifetime trends in weight, rather than single measures, might predict prognosis better and help untangle these apparent contradictions. Thus, the need arises to properly monitor BMI trends in affected dementia patients. Registries can include BMI, improving the management of dementia patients throughout the whole course of the disease. The role of central obesity and systemic inflammation on brain pathology and cognitive decline are discussed in this review. Understanding the life-course changes in BMI and their influence on dementia risk, cognitive prognosis and mortality after diagnosis may provide new insights into the underlying pathophysiology of dementia and shape possible intervention and treatment strategies.
- MeSH
- Dementia diagnosis epidemiology MeSH
- Body Mass Index * MeSH
- Cognition physiology MeSH
- Humans MeSH
- Nutritional Status MeSH
- Obesity complications metabolism MeSH
- Risk Factors MeSH
- Sex Factors MeSH
- Aging physiology MeSH
- Body Weight MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH