Women and dementia – not forgotten

Objectives

To inform our understanding of gender, sex and dementia for women's health and highlight both current and emerging issues. The purpose of this article is to provide policy makers with an improved understanding of the sex-specific and gender dimensions that exist to help formulate more effective and targeted health and social care policies.

Methods

The findings, from which this article is formed, were reported in the form of an evidence review which included both qualitative and quantitative studies from academic, clinical, research and grey literature. The issue of dementia was approached through the prism of sex and gender, in an attempt to understand the complex interaction between biologically and socially constructed roles.

Findings

There continues to be a pressing need to raise awareness of the impact of discrimination, exclusion and stigma associated with dementia and the impact for women in particular.While the ‘feminisation of ageing’ is a widely recognised trend, hitherto a comprehensive approach to the impact of dementia on women remains largely unexplored with regards to research and policy impact. Women face a ‘triple jeopardy’ as a result of the associated stigma attached to their age, gender and decline in cognitive functions.The need for further research of the sex and gender specific risk factors for dementia is highlighted alongside the need for greater evidence on diagnosis, treatment and response.The findings also expose the gender specific nature of unpaid care and the associated consequences for women as a result.

Conclusions

Based on analysis of the available data and assisted by the gender lens tool, the findings presented in this article posit that women across many parts of the world are and will continue to disproportionately bear the burden of dementia, with particular regard to either living with dementia and/or caring for family members with dementia.     

Are patients with dementia treated as well as patients without dementia for hypertension,diabetes, and hyperlipidaemia?

Background

Patients suffering from dementia are at risk of being treated differently by GPs from patients without it. Explanations for this could be stigmatisation, treatment with a palliative approach, and the result of the disease process.

Aim

To ascertain whether patients with dementia are treated differently, the index diseases of hypertension, diabetes, and hyperlipidaemia were used to measure care.

Design of study

Retrospective matched control study.

Setting

German general practice.

Method

Sixteen GP practices recruited all their patients with dementia and at least one of the index diseases. Patients without dementia but only the index diseases were matched for age, sex, index disease, and practice, resulting in 216 pairs of patients with and without dementia. From the files, blood pressure, blood sugar/glycated haemoglobin, cholesterol, the dates of measurement, the number of doctor–patient contacts, and the prescribed medication to treat the three conditions under scrutiny were documented. For analysis, t-tests and χ²-tests were used.

Results

No differences were found in treatment outcomes between the two patients groups, except one significant difference: one of the two documented systolic blood pressure values is lower in the dementia group. Furthermore, patients with dementia more often do not receive any medication or are treated with low-priced medications for hypertension (nearly significant).

Conclusion

GPs do not seem to treat patients with dementia differently. The use of lower-priced antihypertensive medication could be the only indication for some kind of difference in approach.     

Incidence of dementia: does gender make a difference?

Several studies suggested that women are at higher risk of dementia than men. However, that was based on rather limited data. We investigated possible gender differences in the incidence of dementia, Alzheimer's disease and vascular dementia, in the Rotterdam Study, a large population based prospective cohort study in the Netherlands of 7,046 persons aged 55 years and older, free of dementia at baseline. In 40,441 person-years of follow-up (mean 5.7 years) we identified 395 new cases of dementia (overall incidence: 9.8 per 1,000 person-years). Alzheimer's disease was the most frequent subtype of dementia (293 cases; 7.2 per 1,000). Vascular dementia was diagnosed in 57 participants (1.5 per 1,000). Overall, dementia incidence was similar for men and women (rate ratio women versus men: 1.00, 95% CI: 0.80-1.24). However, after 90 years of age dementia incidence declined in men but not in women (rate ratio 2.61, 95% CI: 1.04-6.56), in particular for Alzheimer's disease (rate ratio 5.79, 95% CI: 1.40-23.90). The overall incidence of vascular dementia was lower in women than in men (rate ratio 0.57, 95% CI: 0.34-0.97). This large population-based study suggests no gender differences in the incidence of dementia up to high age. After 90 years of age the incidence of Alzheimer's disease is higher for women than for men. The incidence of vascular dementia is higher for men than for women in all age groups.     

The epidemiologic study of dementia: a life-long quest?

Based on many experimental and observational studies we now understand that neurodegenerative brain changes begin by middle age. Characteristics of the risk factors for these brain changes may also change with age. A review is conducted of studies that report on the association of mid-life risk factors to late cognitive impairment and dementia. Issues related to the interpretation of the data are discussed. The studies suggest that mid-life cardiovascular risk factors, and in particular elevated levels of blood pressure, increase the risk for late-life cognitive impairment and dementia. Our understanding the contribution of cardiovascular risk factors to late age brain disease has been helped tremendously by prospective studies with long follow-up. To better understand which risk factors lead to disease initiation, progression and prognosis, a life course approach to the epidemiologic study of dementia is needed.     

Amyloid β concentrations in older people with Down syndrome and dementia

People with Down syndrome develop Alzheimer's disease with an early age of onset. Plasma amyloid beta (Aβ) levels were measured in individuals with Down syndrome who were over the age of 40. No associations between age and Aβ1–40 and Aβ1–42 concentrations were found and nor were Aβ1–40 and Aβ1–42 levels found to vary between those with Alzheimer's-type dementia and those without dementia. The APOE genotype was not found to have an impact upon Aβ1–40 or Aβ1–42 concentrations. These data suggest that other factors play important roles in determining the onset and progression of dementia in the Down syndrome population.     

Apolipoprotein ɛ4 and neuropsychological performance in Alzheimer's disease and vascular dementia

The apolipoprotein (APOE) ?4 allele is a genetic risk factor for the development of Alzheimer's disease (AD). It has also been associated with vascular dementia (VaD) in some but not all studies. Previous studies have examined the role of APOE in predicting performance on cognitive tests in both demented and non-demented populations. In cognitively intact individuals, statistically significant group differences between APOE ?4 carriers and non-carriers have been demonstrated for several cognitive domains. In AD studies of the impact of APOE ?4 on cognition have been conflicting while no previous study has assessed cognition and impact of APOE ?4 in VaD. In this study we investigated the impact of APOE ?4 on performance in neuropsychological tests including information processing speed in patients with mild-moderate AD and VaD. We incorporated both computerized and pen and paper tests to ensure a sensitive method of assessing cognition. 109 patients participated in the study (VaD = 41, AD = 68). Neurocognitive performance of 44 ?4 present AD patients was compared to 24 ?4absent patients and performance of 23 ?4 present VaD patients was compared to 18 ?4 absent patients. There was evidence that APOE ?4 conferred a risk of poorer cognitive functioning in both patient groups. In the AD group presence of ?4 conferred a negative impact on some measures of speed of information processing and immediate recall while in the VaD group ?4 present patients had evidence of poorer accuracy on tasks such as choice reaction time and spatial working memory. In AD and VaD groups ?4 present patients showed impairment in selective attention. These findings provide further support of the negative impact of the ?4 allele in cognition.     

Is apolipoprotein E4 an important risk factor for vascular dementia?

Despite the fact that vascular dementia (VaD) represents the seconding leading cause of dementia in the USA, behind only Alzheimer’s disease (AD), there remains a lack of consensus on the pathological criteria required for diagnosis of this disease. A number of clinical diagnostic criteria exist but are poorly validated and inconsistently applied. It is clear that vascular risk factors play an important role in the etiology of VaD, including hypertension, stroke, diabetes, and atherosclerosis. Vascular risk factors may increase the risk for VaD by promoting inflammation, cerebral vascular disease, white matter lesions, and hippocampal sclerosis. Because vascular risk factors seem to impart a high degree of risk for conferring VaD, it seems logical that the apolipoprotein E (APOE) status of individuals may be important. APOE plays a critical role in transporting cholesterol in and out of the CNS and in AD it is known that harboring the APOE allele increases the risk of AD perhaps due to the improper functioning of this protein. The purpose of this review is to examine the important pathological features and risk factors for VaD and to provide a critical assessment of the current literature regarding whether or not apoE4 also confers disease risk in VaD. The preponderance of data suggests that harboring one or both APOE4 alleles elevates the risk for VaD, but not to the same extent as found in AD.     

A possible cause of Alzheimer’s dementia – Industrial soy foods

Alzheimer’s data indicate that at present, approximately one new case of this form of dementia is identified in the USA every 68 s and that by 2050 the incidence will be about every 33 s, with projections from the Alzheimer Association (USA) indicating that nearly 25% of Americans will be affected by Alzheimer’s dementia by 2031. Despite the numerous advances in medical science and neurological research, the causes are still unknown and the incidence is not decreasing or levelling out. Most research on the causes of Alzheimer’s dementia indicates the possible roles of viruses, obesity, physical inactivity, diabetes, psychological depression, high blood pressure, frequent inflammation, environmental or domestic chemicals and toxins, or inescapable genetic factors. Alzheimer’s, being the degeneration of parts of the neural pathways in the brain, may indeed involve neuro-toxic compounds that can bypass the blood–brain barrier. Therefore, it is necessary to examine what is prolific in the environment and, in particular, the food supply. One of the many suggestions in the literature is the ingestion of food items derived from unfermented soybean products; the anti-thyroid, anti-nutrient, and endocrine disruption properties of soy can have a deleterious effect in many individuals. Among the many theories and different factors that may be involved in dementiae, soy consumption may be a significant contributor to Alzheimer’s dementia, and it cannot be excluded as a possible contributing cause. Our hypothesis argues that consumption of soy food products may contribute to the increasing incidence of Alzheimer’s dementia and other dementiae.     

Is ApoE gene a risk factor for vascular dementia in Han Chinese?

We have compared the apolipoprotein E (ApoE) genotypes of Han Chinese with late-onset sporadic Alzheimer's disease (LOAD, n=191), and vascular dementia (VaD, n=124) to controls (n=218) with a similar age distribution. The frequency of ApoE epsilon4 allele in the LOAD group was significantly higher than that in the control group (30.1% versus 10.55%, p<10-7). The risk rate of LOAD was 3.5 times higher for carriers with at least one ApoE epsilon4 allele than for non-epsilon4 bearing controls. ApoE epsilon4 allele was also significantly associated with vascular dementia (OR=1.75, p=0.026). Our findings support previous reports of a positive association between ApoE epsilon4 and both Alzheimer's disease and vascular dementia in Han Chinese.     

How can elderly apolipoprotein E ε4 carriers remain free from dementia?

Apolipoprotein E (APOE) ε4 is a major risk factor for Alzheimer's disease (AD) and dementia, but not all ε4 carriers develop dementia. We sought to identify factors that may play a role in modifying the risk of dementia due to ε4. A cognitively intact cohort (n = 932, age ≥ 75) was followed for 9 years to detect incident dementia cases. At baseline, information on education, leisure activities, and vascular risk factors was collected, and APOE was genotyped. During the follow-up, 324 subjects developed dementia, including 247 AD cases. The hazard ratio (HR, 95% confidence interval [95% CI]) of dementia related to the ε4 was 1.39 (1.11–1.76), while the risk was reduced when ε4 carriers had high education, no vascular risk factors, or high score of leisure activities. Among ε4 carriers, the multiadjusted HRs of dementia that were associated with high education, high level of leisure activities, and absence of vascular risk factors were 0.59 (0.40–0.87), 0.49 (0.29–0.85), and 0.61 (0.41–0.90), respectively. The ε4 carriers with these factors had about 1.2 years delayed time to dementia onset compared with those without these factors. High education, active leisure activities, or maintaining vascular health seems to reduce the risk of dementia related to APOE ε4. The ε4 carriers with these characteristics appear to have similar dementia-free survival time to non-ε4 carriers.     

Improving actigraphic sleep estimates in insomnia and dementia: how many nights?

In order to investigate how the duration of actigraphic recordings affects the reliability of actigraphic estimates of sleep and 24-h activity rhythm variables, two to 3 weeks of actigraphy were recorded, from which pairs of variables derived from two periods of increasing length (1-10 days) were compared. Two groups were studied: (1) 10 subjects suffering from primary insomnia; and (2) 12 demented elderly subjects living semi-independently in group care facilities of homes for the elderly. Actigraphic estimates of primary measures of sleep (duration and efficiency) and of the 24-h activity pattern (interdaily stability, intradaily variability and amplitude) were calculated on variable lengths of the actigraphic recordings. The average absolute difference of two estimates decreased - and reliability increased - strongly with an increasing number of days analysed. An acceptable reliability of the interdaily stability estimate required more than 7 days of recording. It can be concluded that a valuable improvement in the reliability of actigraphic sleep estimates can be obtained by simply increasing the number of recording nights. The results support the importance of day-to-day variability in insomnia and dementia that has already been previously noted by others, and even suggest the presence of 'week-to-week' variability. This variability may have been involved in the equivocal results of treatment studies in insomnia and dementia where outcome measures were based on a limited number of nights. Such studies could profit from extension of the recording duration to, e.g. 2 weeks, and from the inclusion of variability measures as measures of clinical interest.     

Do alcohol and cocaine abuse alter the course of HIV-associated dementia complex?

Although psychoactive drugs are commonly used by AIDS patients, it is unclear whether commonly abused drugs, such as cocaine and ethanol, affect the course of HIV-associated dementia (HADC). Epidemiological studies have resulted in conflicting conclusions as to what role, if any, abused drugs play in HADC. In this review we discuss the clinical and pathological evidence that cocaine and ethanol might exacerbate the detrimental effects of HIV infection on the brain. We also review studies of cocaine and ethanol effects on various components of the immune system both in the presence and absence of retroviral infection. Data from these studies indicate that cocaine and ethanol have profound effects on the immune system that, in many respects, are enhanced by retroviral infection. We conclude that abused drugs likely affect the course of HADC but that proof awaits an examination of their interactive effects in an appropriate in vivo system of retroviral encephalitis.     

Exercise-induced brain-derived neurotrophic factor expression: Therapeutic implications for Alzheimer’s dementia

Emerging evidence indicates that moderate intensity aerobic exercise is positively correlated with cognitive function and memory. However, the exact mechanisms underlying such improvements remain unclear. Recent research in animal models allows proposition of a pathway in which brain-derived neurotrophic factor (BDNF) is a key mediator. This perspective draws upon evidence from animal and human studies to highlight such a mechanism whereby exercise drives synthesis and accumulation of neuroactive metabolites such as myokines and ketone bodies in the periphery and in the hippocampus to enhance BDNF expression. BDNF is a neurotrophin with well-established properties of promoting neuronal survival and synaptic integrity, while its influence on energy transduction may provide the crucial link between inherent vascular and metabolic benefits of exercise with enhanced brain function. Indeed, BDNF mRNA and protein is robustly elevated in rats following periods of voluntary exercise. This was also correlated with improved spatial memory, while such benefits were abolished upon inhibition of BDNF signaling. Similarly, both BDNF and cardiovascular fitness arising from aerobic exercise have been positively associated with hippocampal volume and function in humans. We postulate that exercise will attenuate cortical atrophy and synaptic loss inherent to neurodegenerative disorders - many of which also exhibit aberrant down-regulation of BDNF. Thus, the proposed link between BDNF, exercise and cognition may have critical therapeutic implications for the prevention and amelioration of memory loss and cognitive impairment in Alzheimer’s disease and associated dementias.     

Life span and synapses: will there be a primary senile dementia?

In the course of normal aging from about age 20 to 100, the population density of neocortical synapses declines toward, but not reaching, the level found in Alzheimer disease. A deficiency of synapses at birth or due to inadequate childhood education would theoretically cause the synaptic slope to reach the Alzheimer level early. The normal slope would cross into that dementia range at about age 130, resulting in true primary senile dementia without regard to the presence of plaques and tangles.     

Lost for words or loss of memories? Autobiographical memory in semantic dementia

Recent reports have suggested that patients with semantic dementia show a loss of early (remote) auto-biographical memories with pronounced sparing of recent memories (Graham & Hodges, 1997; Snowden, Griffiths, & Neary, 1996), i.e., a 'reversed' temporal gradient or 'Ribot effect'. At first sight, these findings suggest that the deficits in 'semantic' dementia go beyond the semantic domain, involving aspects of autobiographical (episodic) memory. It has also been proposed that there is a 'step-like' function with personal memories preserved for 18 months to 2 years in the immediate past. This view is consistent with the theory that the hippocampal complex/medial temporal lobe (relatively intact in semantic dementia) plays a time-limited role in the acquisition and storage of memories, while the temporal neocortex (damaged in semantic dementia) is required for long-term storage and retrieval. In this study we ask whether (a) previous tests have underestimated the integrity of remote memory in semantic dementia as a result of not allowing for these patients' comprehension and language production difficulties, and (b) whether a recency effect, if obtained, is genuinely step-like or more graded. We used a cued autobiographical memory interview with semantic dementia patient, IH, to examine the effect of providing increasingly specific lexical cues to probe salient events throughout his lifespan. Results demonstrated that the provision of specific cues enabled IH to access and express memories from his childhood and early adulthood as well as from more recent times. There was a gentle recency effect only for intermediate levels of cueing, indicating that recent memories were easier to retrieve and/or express in the absence of specific cues, but this effect was graded, with no evidence of a step-like cut-off at 18 months or 2 years before testing. In brief, our findings are consistent with the view that the deficits in semantic dementia are predominantly or exclusively semantic, rather than involving the storage of autobiographical memories per se.