Factors Associated with Participation in a Multidomain Web-Based Dementia Prevention Trial: Evidence from Maintain Your Brain (MYB).

BACKGROUND: The Maintain Your Brain (MYB) trial aims to prevent cognitive decline and dementia through multidomain, web-based risk-reduction. To facilitate translation, it is important to understand drivers of participation. OBJECTIVE: To describe characteristics associated with participation in MYB. METHODS: This was an observational ancillary study of MYB, a randomized controlled trial nested within the 45 and Up Study in New South Wales, Australia. We linked 45 and Up Study survey and MYB participation data. The study cohort comprised 45 and Up Study participants, aged 55-77 years at 1 January 2018, who were invited to participate in MYB. 45 and Up Study participant characteristics and subsequent MYB consent and participation were examined. RESULTS: Of 98,836 invited, 13,882 (14%) consented to participate and 6,190 participated (6%). Adjusting for age and sex, a wide range of factors were related to participation. Higher educational attainment had the strongest relationship with increased MYB participation (university versus school non-completion; AdjOR = 5.15; 95% CI:4.70-5.64) and lower self-rated quality of life with reduced participation (Poor versus Excellent: AdjOR = 0.19; 95% CI:0.11-0.32). A family history of Alzheimer's disease was related to increased participation but most other dementia risk factors such as diabetes, obesity, stroke, high blood pressure, and current smoking were associated with reduced participation. CONCLUSION: Higher socio-economic status, particularly educational attainment, is strongly associated with engagement in online dementia prevention research. Increasing population awareness of dementia risk factors, and better understanding the participation barriers in at-risk groups, is necessary to ensure online interventions are optimally designed to promote maximum participation.

Maintain Your Brain: Protocol of a 3-Year Randomized Controlled Trial of a Personalized Multi-Modal Digital Health Intervention to Prevent Cognitive Decline Among Community Dwelling 55 to 77 Year Olds.

BACKGROUND: Maintain Your Brain (MYB) is a randomized controlled trial of an online multi-modal lifestyle intervention targeting modifiable dementia risk factors with its primary aim being to reduce cognitive decline in an older age cohort. METHODS: MYB aims to recruit 8,500 non-demented community dwelling 55 to 77 year olds from the Sax Institute's 45 and Up Study in New South Wales, Australia. Participants will be screened for risk factors related to four modules that comprise the MYB intervention: physical activity, nutrition, mental health, and cognitive training. Targeting risk factors will enable interventions to be personalized so that participants receive the most appropriate modules. MYB will run for three years and up to four modules will be delivered sequentially each quarter during year one. Upon completing a module, participants will continue to receive less frequent booster activities for their eligible modules (except for the mental health module) until the end of the trial. DISCUSSION: MYB will be the largest internet-based trial to attempt to prevent cognitive decline and potentially dementia. If successful, MYB will provide a model for not just effective intervention among older adults, but an intervention that is scalable for broad use.

Mortality in a cohort of remote-living Aboriginal Australians and associated factors.

OBJECTIVES: We aimed to describe mortality in a cohort of remote-living Aboriginal Australians using electronic record linkage. METHODS: Between 2004 and 2006, 363 Aboriginal people living in remote Western Australia (WA) completed a questionnaire assessing medical history and behavioural risk factors. We obtained mortality records for the cohort from the WA Data Linkage System and compared them to data for the general population. We used Cox proportional hazards regression to identify predictors of mortality over a 9-year follow-up period. RESULTS: The leading causes of mortality were diabetes, renal failure, and ischaemic heart disease. Diabetes and renal failure accounted for 28% of all deaths. This differed from both the Australian population as a whole, and the general Indigenous Australian population. The presence of chronic disease did not predict mortality, nor did behaviours such as smoking. Only age, male sex, poor mobility, and cognitive impairment were risk factors. CONCLUSIONS: To reduce premature mortality, public health practitioners should prioritise the prevention and treatment of diabetes and renal disease in Aboriginal people in remote WA. This will require a sustained and holistic approach.

Relationship between monocyte-platelet aggregation and endothelial function in middle-aged and elderly adults.

Low-grade inflammation, endothelial dysfunction, and platelet hyper-reactivity to agonists are associated with an increased risk of cardiovascular events. In vitro and animal studies infer an inverse mechanistic relationship between platelet activation and the production of endothelium-derived nitric oxide and prostacyclin. This concept is supported by evidence of an inverse relationship between endothelial function and platelet activation in high-risk cardiac patients. The aim of this study was to investigate what relationship, if any, exists between platelet and endothelial function in healthy, middle-aged, and elderly adults. In 51 participants (18 male, 33 post menopausal female), endothelial function was assessed by flow-mediated dilation (FMD). Platelet function was assessed by flow cytometric determination of glycoprotein IIb/IIIa activation (measured by PAC-1 binding), granule exocytosis (measured by surface P-selectin expression), and monocyte-platelet aggregates (MPAs), with and without stimulation by canonical platelet agonists adenosine diphosphate (ADP), arachidonic acid (AA), and collagen. Correlation analysis indicated there was no significant (all P => 0.05) relationship between FMD and any marker of in vivo platelet activation (MPAs R = 0.193, PAC-1 R = -0.113, anti-CD62P R = -0.078) or inducible platelet activation by ADP (MPA R = -0.128, anti-CD62P R = -0.237), AA (MPA R = -0.122, PAC-1 R = -0.045, anti-CD62P R = -0.142), or collagen (MPA R = 0.136, PAC-1 R = 0.174, anti-CD62P R = -0.077). Our findings contrast with two previous studies performed in high-risk cardiac patients, which reported inverse relationships between platelet activation and endothelial function, suggesting that some compensatory redundancy may exist in the relationship between platelet and endothelial function in preclinical populations.

What is frontotemporal dementia?

Frontotemporal dementia (FTD) is the clinical manifestation of progressive nerve cell loss in the frontal and anterior temporal lobes. It represents the second most frequent form of early-onset dementia. The two major types of FTD are determined by the localisation of the underlying pathology. The behaviour variant is characterised by disinhibition, socially inappropriate manners, loss of empathy, blunting of affect and hyperorality. Key features of the language variant are either non-fluent effortful speech and grammatical errors or impaired word finding and loss of meaning of words and objects. Histopathological changes are characterised by the abnormal processing of proteins including microtubule associated protein Tau, transactive response DNA-binding protein, and tumour-associated protein fused in sarcoma. The familial forms of FTD are caused by mutations in 5 genes. The diagnosis of FTD rests on careful history and psychiatric, neuropsychological and neurological examination supported by laboratory assessments and brain imaging. The management requires an interdisciplinary approach involving the carer and using non-pharmacological approaches in the first line. Current antidementia drugs, including cholinesterase inhibitors and memantine, have no consistent positive effects in FTD. Behavioural symptoms may respond favourably to selective serotonergic antidepressants. Antipsychotic agents should be used with caution regarding motor, cardiovascular and mortality risks.

Factors associated with suicidal thoughts in a large community study of older adults.

BACKGROUND: Thoughts about death and self-harm in old age have been commonly associated with the presence of depression, but other risk factors may also be important. AIMS: To determine the independent association between suicidal ideation in later life and demographic, lifestyle, socioeconomic, psychiatric and medical factors. METHOD: A cross-sectional study was conducted of a community-derived sample of 21 290 adults aged 60-101 years enrolled from Australian primary care practices. We considered that participants endorsing any of the four items of the Depressive Symptom Inventory -Suicidality Subscale were experiencing suicidal thoughts. We used standard procedures to collect demographic, lifestyle, psychosocial and clinical data. Anxiety and depressive symptoms were assessed with the Hospital Anxiety and Depression Scale. RESULTS: The 2-week prevalence of suicidal ideation was 4.8%. Male gender, higher education, current smoking, living alone, poor social support, no religious practice, financial strain, childhood physical abuse, history of suicide in the family, past depression, current anxiety, depression or comorbid anxiety and depression, past suicide attempt, pain, poor self-perceived health and current use of antidepressants were independently associated with suicidal ideation. Poor social support was associated with a population attributable fraction of 38.0%, followed by history of depression (23.6%), concurrent anxiety and depression (19.7%), prevalent anxiety (15.1%), pain (13.7%) and no religious practice (11.4%). CONCLUSIONS: Prevalent and past mood disorders seem to be valid targets for indicated interventions designed to reduce suicidal thoughts and behaviour. However, our data indicate that social disconnectedness and stress account for a larger proportion of cases than mood disorders. Should these associations prove to be causal, then interventions that succeeded in addressing these issues would contribute the most to reducing suicidal ideation and, possibly, suicidal behaviour in later life.

Protocol for a randomized controlled trial evaluating the effect of physical activity on delaying the progression of white matter changes on MRI in older adults with memory complaints and mild cognitive impairment: the AIBL Active trial.

BACKGROUND: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging (MRI). METHODS/DESIGN: This single-blind randomized controlled trial (RCT) is offered to 156 participants, aged 60 and older, in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). Participants must have SMC with or without MCI and at least one VRF. The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI (Fitness for the Ageing Brain Study). It comprises 24 months of moderate, home-based PA (150 minutes per week) and a behavioral intervention package. The primary outcome measure will be change in WMH after 24 months on MRI. Cognition, quality of life, functional fitness, level of physical activity, plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography (PET) imaging comprise secondary measures. DISCUSSION: Currently, there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk. Should our findings show that physical activity can slow down the progression of WMH, this RCT would provide an important proof of concept. Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer's disease pathologies. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000612910.

Homocysteine, grey matter and cognitive function in adults with cardiovascular disease.

BACKGROUND: Elevated total plasma homocysteine (tHcy) has been associated with cognitive impairment, vascular disease and brain atrophy. METHODS: We investigated 150 volunteers to determine if the association between high tHcy and cerebral grey matter volume and cognitive function is independent of cardiovascular disease. RESULTS: Participants with high tHcy (≥15 µmol/L) showed a widespread relative loss of grey matter compared with people with normal tHcy, although differences between the groups were minimal once the analyses were adjusted for age, gender, diabetes, hypertension, smoking and prevalent cardiovascular disease. Individuals with high tHcy had worse cognitive scores across a range of domains and less total grey matter volume, although these differences were not significant in the adjusted models. CONCLUSIONS: Our results suggest that the association between high tHcy and loss of cerebral grey matter volume and decline in cognitive function is largely explained by increasing age and cardiovascular diseases and indicate that the relationship is not causal.

Socioeconomic disadvantage increases risk of prevalent and persistent depression in later life.

BACKGROUND: Depression is more frequent in socioeconomically disadvantaged than affluent neighbourhoods, but this association may be due to confounding. This study aimed to determine the independent association between socioeconomic disadvantage and depression. METHODS: We recruited 21,417 older adults via their general practitioners (GPs) and used the Patient Health Questionnaire (PHQ-9) to assess clinically significant depression (PHQ-9≥10) and major depressive symptoms. We divided the Index of Relative Socioeconomic Disadvantage into quintiles. Other measures included age, gender, place of birth, marital status, physical activity, smoking, alcohol use, height and weight, living arrangements, early life adversity, financial strain, number of medical conditions, and education of treating GPs about depression and self-harm behaviour. After 2 years participants completed the PHQ-9 and reported their use of antidepressants and health services. RESULTS: Depression affected 6% and 10% of participants in the least and the most disadvantaged quintiles. The proportion of participants with major depressive symptoms was 2% and 4%. The adjusted odds of depression and major depression were 1.4 (95% confidence interval, 95%CI=1.1-1.6) and 1.8 (95%CI=1.3-2.5) for the most disadvantaged. The adjusted odds of persistent major depression were 2.4 (95%CI=1.3-4.5) for the most disadvantaged group. There was no association between disadvantage and service use. Antidepressant use was greatest in the most disadvantaged groups. CONCLUSIONS: The higher prevalence and persistence of depression amongst disadvantaged older adults cannot be easily explained by confounding. Management of depression in disadvantaged areas may need to extend beyond traditional medical and psychological approaches.

Effects of anticholinergic drugs on cognitive function in older Australians: results from the AIBL study.

BACKGROUND/AIMS: The nature and extent of adverse cognitive effects due to the prescription of anticholinergic drugs in older people with and without dementia is unclear. METHODS: We calculated the anticholinergic load (ACL) of medications taken by participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing, a cohort of 211 Alzheimer's disease (AD) patients, 133 mild cognitive impairment (MCI) patients and 768 healthy controls (HC) all aged over 60 years. The association between ACL and cognitive function was examined for each diagnostic group (HC, MCI, AD). RESULTS: A high ACL within the HC group was associated with significantly slower response speeds for the Stroop color and incongruent trials. No other significant relationships between ACL and cognition were noted. CONCLUSION: In this large cohort, prescribed anticholinergic drugs appeared to have modest effects upon psychomotor speed and executive function, but not on other areas of cognition in healthy older adults.

24-month effect of smoking cessation on cognitive function and brain structure in later life.

BACKGROUND: Observational studies investigating the association between smoking, cognitive decline and dementia have produced conflicting results. We completed this trial to determine if smoking cessation decreases the progression of cognitive decline in later life. METHODS: We recruited older smokers (n=229) and never smokers (n=98) and invited smokers to join a smoking cessation trial. The primary outcome of interest was change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) scores over 24 months. Secondary measures included the Logical Memory test and changes in gray matter density. Successful smoking cessation was defined as a minimum of 547 smoking free days during follow up. RESULTS: The ADAS-cog scores of unsuccessful quitters (UQ) increased (i.e., became worse) 1.1±0.3 and 1.2±0.4 points more than the scores of never smokers (NS) (p=0.001) and successful quitters (SQ) (p=0.006) respectively over the 24 months of follow up. Similarly, the scores of UQ declined (i.e., became worse) relative to NS on measures of immediate (p=0.004) and delayed recall (p=0.029). All analyses were adjusted for age, years of education, baseline cognitive performance, alcohol use, depression scores, and the presence of chronic respiratory disease. Thirty-six NS, 18 SQ and 48 UQ completed the imaging substudy. Compared with NS, UQ showed a disproportional loss of gray matter density in the right thalamus, right and left inferior semi-lunar lobule, as well as left superior and inferior parietal lobule over 24 months. SQ showed loss of gray matter compared with NS in the right middle and inferior occipital gyri, right and left culmen, and the left superior frontal gyrus. We did not find any brain regions in which UQ had lost more gray matter than SQ over 2 years. CONCLUSION: These results are consistent with the hypothesis that smoking causes cognitive decline and loss of gray matter tissue in the brain over time.

A practical approach to assess depression risk and to guide risk reduction strategies in later life.

BACKGROUND: Many factors have been associated with the onset and maintenance of depressive symptoms in later life, although this knowledge is yet to be translated into significant health gains for the population. This study gathered information about common modifiable and non-modifiable risk factors for depression with the aim of developing a practical probabilistic model of depression that can be used to guide risk reduction strategies. METHODS: A cross-sectional study was undertaken of 20,677 community-dwelling Australians aged 60 years or over in contact with their general practitioner during the preceding 12 months. Prevalent depression (minor or major) according to the Patient Health Questionnaire (PHQ-9) assessment was the main outcome of interest. Other measured exposures included self-reported age, gender, education, loss of mother or father before age 15 years, physical or sexual abuse before age 15 years, marital status, financial stress, social support, smoking and alcohol use, physical activity, obesity, diabetes, hypertension, and prevalent cardiovascular diseases, chronic respiratory diseases and cancer. RESULTS: The mean age of participants was 71.7 ± 7.6 years and 57.9% were women. Depression was present in 1665 (8.0%) of our subjects. Multivariate logistic regression showed depression was independently associated with age older than 75 years, childhood adverse experiences, adverse lifestyle practices (smoking, risk alcohol use, physical inactivity), intermediate health hazards (obesity, diabetes and hypertension), comorbid medical conditions (clinical history of coronary heart disease, stroke, asthma, chronic obstructive pulmonary disease, emphysema or cancers), and social or financial strain. We stratified the exposures to build a matrix that showed that the probability of depression increased progressively with the accumulation of risk factors, from less than 3% for those with no adverse factors to more than 80% for people reporting the maximum number of risk factors. CONCLUSIONS: Our probabilistic matrix can be used to estimate depression risk and to guide the introduction of risk reduction strategies. Future studies should now aim to clarify whether interventions designed to mitigate the impact of risk factors can change the prevalence and incidence of depression in later life.

Factors associated with dementia in Aboriginal Australians.

OBJECTIVE: Although the prevalence of dementia in remote living Aboriginal Australians is one of the highest in the world, the factors associated with dementia in this population are yet to be examined. This study was designed to determine the demographic, lifestyle and clinical factors associated with dementia in Aboriginal Australians living in the Kimberley region of Western Australia. METHOD: A total of 363 Aboriginal Australians aged over 45 years from the Kimberley region were selected by semi-purposeful sampling. The factors analysed for association with dementia were age, sex, education, smoking, chewing tobacco, alcohol, head injury, heart disease, hypertension, diabetes, previous stroke, epilepsy, falls, mobility, incontinence, urinary problems, vision and hearing. This exposure data was collected from participants' and informants' reports using the Kimberley Indigenous Cognitive Assessment and specialist review, and medical records. RESULTS: Factors associated with dementia included older age, male gender (OR 3.1, 95%CI 1.4, 6.8) and no formal education (OR 2.7, 95%CI 1.1, 6.7) and after adjusting for age, sex and education, dementia was associated with current smoking (OR 4.5, 95%CI 1.1, 18.6), previous stroke (OR 17.9, 95%CI 5.9, 49.7), epilepsy (OR 33.5, 95%CI 4.8, 232.3), head injury (OR 4.0, 95%CI 1.7, 9.4), and poor mobility, incontinence and falls. CONCLUSIONS: Interventions aimed at better management or prevention of the modifiable factors identified could reduce dementia risk in Aboriginal populations.

The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease.

BACKGROUND: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer's disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants. METHODS: Volunteers underwent a screening interview, had comprehensive cognitive testing, gave 80 ml of blood, and completed health and lifestyle questionnaires. One quarter of the sample also underwent amyloid PET brain imaging with Pittsburgh compound B (PiB PET) and MRI brain imaging, and a subgroup of 10% had ActiGraph activity monitoring and body composition scanning. RESULTS: A total of 1166 volunteers were recruited, 54 of whom were excluded from further study due to comorbid disorders which could affect cognition or because of withdrawal of consent. Participants with AD (211) had neuropsychological profiles which were consistent with AD, and were more impaired than participants with mild cognitive impairment (133) or healthy controls (768), who performed within expected norms for age on neuropsychological testing. PiB PET scans were performed on 287 participants, 100 had DEXA scans and 91 participated in ActiGraph monitoring. CONCLUSION: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD. They will be reassessed at 18-month intervals in order to determine the predictive utility of various biomarkers, cognitive parameters and lifestyle factors as indicators of AD, and as predictors of future cognitive decline.

Smoking is associated with reduced cortical regional gray matter density in brain regions associated with incipient Alzheimer disease.

OBJECTIVES: The results of observational studies suggest that smoking increases the risk of Alzheimer disease (AD). The authors designed this study to determine if older people who smoke have decreased gray matter density in brain regions associated with incipient AD. METHODS: The authors recruited 39 pairs (N = 78) of smokers/never-smokers 70 to 83 years of age who were matched for age, sex, education, and handedness. Participants were free of clinically significant cognitive impairment, depression, stroke, or other serious medical conditions. Gray matter density was determined by voxel-based morphometry using statistical parametric mapping of T1-weighted magnetic resonance images. RESULTS: Smokers had decreased gray matter density in the posterior cingulum and precuneus (bilateral), right thalamus, and frontal cortex (bilateral) compared with never-smokers. CONCLUSIONS: Smoking is associated with decreased gray matter density in brain regions previously associated with incipient AD. Longitudinal investigations are required to clarify whether these changes are progressive in nature.

Effectiveness of a smoking cessation intervention in older adults.

AIMS: To: (a) identify characteristics of older smokers considering cessation of smoking; (b) evaluate a cessation intervention plus access to nicotine replacement therapy (NRT); (c) identify predictors of those who successfully quit; and (d) evaluate the effectiveness of the intervention in those AGED >or = 75 years. DESIGN: Self-selection of: (a) a cessation of smoking programme; or (b) ongoing smoking. SETTING: Teaching hospital, Perth, Western Australia. PARTICIPANTS: A larger study recruited smokers and never smokers: from this the 215 community-dwelling smokers (>or= 5 cigarettes/day) aged >or= 68 years (171 males) were enrolled. INTERVENTION: Brief intervention with telephone support and access to NRT versus no intervention. MEASUREMENTS: (a) Profile of older adults planning to quit smoking compared with continuing smokers; (b) cessation at 6 months defined as 30-day point prevalence validated via expired carbon monoxide; and (c) factors predictive of successful cessation. FINDINGS: There were 165 intervention participants. Compared with the 50 continuing smokers, participants in the intervention were younger and had significantly less years of regular smoking, more previous quit attempts and greater nicotine dependence scores. At 6 months, the point prevalence of ex-smokers was 25% (n = 42) with 20% (n = 33) being abstinent throughout the study. No continuing smoker had ceased smoking. Among the intervention group, logistic regression showed that those who used NRT (OR 4.36), were male (OR 3.17), had higher anxiety (OR 1.67) or rejected 'more colds and coughs' as a reason for quitting (OR 2.91) were more likely to be successful quitters. Of those aged >or= 75 years (n = 77), 25% matched cessation criteria. CONCLUSIONS: Older smokers can be engaged successfully in a brief intervention plus NRT as aids to cessation of smoking. The intervention was also effective in the older subgroup of participants. Social factors may provide an additional means of motivating older smokers to quit.

Healthy mental ageing.

Healthy mental ageing may be defined as the absence of the common disabling mental health problems of older people, especially cognitive decline and depression, accompanied by the perception of a positive quality of life. Older people are particularly prone to negative effects on mental health due to poor physical health. Modifiable aspects of lifestyle have been shown to be associated with healthy mental ageing. These include increased physical activity, intellectual stimulation (including education), avoidance of smoking and various aspects of diet. There is reasonably strong evidence that the treatment of hypertension will decrease the risk of cognitive impairment, and moderate alcohol intake may also have some benefits on cognition. These modifiable lifestyle factors may benefit from deliberate individual and population health promotion strategies to maximize mental health in old age, although to date intervention trials have not been performed to support the evidence obtained from observational studies.

A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: effect on mood, cognition and quality of life.

The results of several observational studies suggest that the use of estrogen replacement is associated with better mood, cognitive function and quality of life. Such findings are consistent with those of laboratory-based research showing that estrogen promotes neuronal sprouting, enhances cholinergic activity in the brain, decreases brain and plasma levels of beta-amyloid, increases serotonin postsynaptic responsivity and the turnover of noradrenaline, and inhibits monoamine oxidase activity. However, the findings from the Women's Health Initiative controlled trial showed that hormone replacement (estrogen plus progestin) not only failed to improve mood, cognition and quality of life but also increased the risk of dementia. At present, there is limited information about the effect of unopposed estradiol replacement therapy (ERT) on the mental health outcomes of women at increased risk of cognitive decline (aged 70 years and over). We designed the present randomized, double-blind, placebo-controlled trial to clarify this issue. One hundred and fifteen women were randomized to treatment with estradiol (n=58; 2mg per day) or placebo for a total period of 20 weeks. The outcomes of interest in this study included changes in the Beck Depression Inventory (BDI) scores between baseline and week 20, as well as changes in quality of life scores (as measured by the SF-36) and cognitive function (CAMCOG, Block Design, Memory for Faces, California Verbal Learning Test (CVLT) and verbal fluency (VF)). Nineteen women treated with estradiol and 10 of those treated with placebo discontinued the use of the medication during trial, most frequently due to adverse reactions (OR=4.11, 95% CI=1.29-15.37). Intention-to-treat analysis showed that the active and placebo groups did not differ in their response to treatment in any of the outcome measures (p>0.05). A separate analysis restricted to women who completed the 20-week-trial produced similar negative results. The results of this trial indicate that the use of a relatively high dosage of unopposed estrogen replacement for 20 weeks is not associated with significant changes in cognitive function, mood and quality of life. Other more efficacious and safer interventions need to be devised with the aim of improving the mental state and quality of life of older women.

Dementia associated with infectious diseases.

At the turn of the last century, infectious diseases represented an important cause of health morbidity and behavioral changes. Neurosyphilis, for example, was relatively common at the time and often led to the development of cognitive impairment and dementia. With the advent of effective antibiotic treatment, the association between infectious diseases and dementia became increasingly less frequent, although a resurgence of interest in this area has taken place during the past 15 years with the emergence of acquired immunodeficiency syndrome (AIDS) and variant Creutzfeldt-Jakob disease (vCJD). This paper reviews the most frequent infectious causes of dementia, including prion diseases, as well as infections caused by herpes virus, human immunodeficiency virus (HIV), toxoplasmosis, cryptococcus, cytomegalovirus, syphilis, borrelia and cysticercosis.

Dementia associated with alcohol and other drug use.

The acute use of alcohol and several other licit and illicit drugs can affect mental state and cognitive function. The chronic use of certain drugs may also increase the risk of cognitive impairment and perhaps dementia in later life. This paper focuses on the long-term cognitive consequences of using alcohol, benzodiazepines, tobacco and cannabis. Currently available evidence indicates that mild to moderate alcohol consumption is not associated with increased risk of cognitive decline and may in fact have a protective effect against dementia, although heavy, long-term consumption is likely to have a negative impact on cognitive function. The degree that alcohol-related cognitive impairment must reach to be classified as dementia is currently obscure. Longer-term smoking is associated with increased risk of cognitive impairment and possibly dementia. The chronic use of benzodiazepines has been associated with increased risk of cognitive impairment but information relating to dementia remains inconclusive. The chronic use of cannabis may impair intellectual abilities but data on this topic remain sparse and difficult to interpret. In conclusion, there is evidence that some drugs contribute to the causal pathway that leads to the development of cognitive impairment but currently available data do not support the introduction of a separate diagnostic category of drug-induced dementia (such as alcohol-related dementia). Health promotion programs designed to decrease tobacco smoking and "harmful" alcohol use (and possibly other drug use) may decrease the burden of cognitive impairment and perhaps dementia in later life.