Urate and risk of Alzheimer's disease and vascular dementia: A population-based study

IntroductionLow serum urate (sU) has been suggested to increase the risk of dementia since a reduction might impair antioxidant capacity. On the other hand, high sU is associated with increased cardiovascular risk which might increase the risk of dementia, especially for vascular dementia.MethodsIn 1968–1969, a population-based sample of 1462 women aged 38 to 60 years was examined and were followed up over 44 years (mean 33.1 years). We examined whether sU (determined in 1968–1969 and 1992–1994) is associated with risk of late-life dementia.ResultsDuring 44 years of follow-up, a higher sU (per standard deviation of 76.5 μmol/L) was associated with lower risk for dementia (n = 320; hazard ratio [HR] 0.81; confidence interval [CI] 0.72–0.91), Alzheimer's disease (n = 152; HR 0.78; CI 0.66–0.91), and vascular dementia (n = 52; HR 0.66; CI 0.47–0.94).DiscussionOur findings support the hypothesis that sU has a protective role in the development of dementia, regardless of dementia subtype. This may have important implications in the treatment of dementia and treatment goals for hyperuricemia in patients with gout.     

Neuropsychological differentiation of Alzheimer's disease from vascular dementia

The purpose of this study was to determine whether cognitive test performances alone could distinguish patients with probable Alzheimer's disease from those with probable vascular dementia. Sixty-eight outpatients with clinical diagnoses of either Alzheimer's disease or vascular dementia were administered a brief battery of neuropsychological tests. Scores from the Boston Naming Test and the Hopkins Verbal Learning Test were identified as most discriminating of the groups. Seventy-seven per cent of the sample was correctly classified by a stepwise discriminant function analysis. Results of this study indicate that selected neuropsychological tests have moderate concurrent utility in the differential diagnosis of dementia.     

Critical Flicker Fusion Threshold in patients with Alzheimer's disease and vascular dementia

BACKGROUND: Critical Flicker Fusion Threshold (CFFT) is a psychophysical threshold and in psychological terms is regarded as a measure of information processing capacity. The test has previously been shown to be a valid and reliable measure of CNS functioning in patients with Alzheimer's disease and may be a useful as a screening measure for the early detection of Alzheimer's disease (AD). METHODS: Consecutive referrals to the Wakefield Memory Clinic who met DSM-IV criteria for AD or vascular dementia (VaD) were invited to take part in the study. A range of neuropsychological tests and CFFT were administered to the two groups using standardised protocols and the ability of these various tests to distinguish between the two conditions was investigated. RESULTS: Forty-six patients were included in the study. Of the various tests, only the descending component of CFFT and word fluency were significantly different in the two groups. In addition, the descending threshold had a sensitivity of 83% and a specificity of 69%. CONCLUSION: CFFT could be useful as a screening instrument for early AD when combined with other measures and could facilitate the decision to commence antidementia treatment at an early stage. Further longitudinal work is needed to establish this.     

Association of depression with Alzheimer's disease and vascular dementia in an elderly Arab population of Wadi-Ara, Israel

OBJECTIVES: Because dementia and depression share common risk factors, we investigated risk factors for depression in Arab subjects with Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: In a cross-sectional population-based study, we conducted a door-to-door survey of all adults over age 60 in an Arab community of rural Israel. We conducted interviews, gave questionnaires, and collected DNA blood specimens for determination of ApoE genotype. RESULTS: Of the 823 individuals in this naturalistic sample, 168 had dementia of Alzheimer's type (DAT) and 49 had VaD. Vascular risk factors, including the ApoE-epsilon4 allele, were more prevalent among VaD than DAT subjects. Depressive symptoms were present in 57% of DAT patients and 86% of VaD patients. Depressed DAT individuals had a greater history of ischemic cardiovascular or cerebrovascular (CV/CBV) disease than non-depressed DAT subjects, but depressed DAT subjects were less likely to have the ApoE-epsilon4 allele. Within the VaD group, there was no difference in the distribution of cardiovascular risk factors in individuals with and without depressive symptoms, and ApoE-epsilon4 was more prevalent among subjects with depressive symptoms. CONCLUSIONS: Depressive symptomatology is prevalent among subjects with dementias in this Arab community. History of CV/CBV is associated with the presence of depressive symptoms in DAT. Further studies are needed to clarify the role of ApoE in depression onset in different ethnic groups with DAT.     

Depression and apathy affect functioning in community active subjects with questionable dementia and mild Alzheimer's disease

BACKGROUND: The relationships between apathy, depression and functional impairment in questionable dementia (QD) and Alzheimer's disease (AD) are complex. This study aimed to explore the interactions between severity of apathy, depression and functional performance; and to investigate the effects of apathy alone, depression alone and coexistence of apathy and depression on the functional performance in subjects with QD and AD. METHODS: One hundred ninety-five subjects with QD and 96 subjects with mild AD were recruited. Apathy and depression were rated using the Neuropsychiatric Inventory and functional disability was measured using the Disability Assessment for Dementia (DAD). RESULTS: Severity of apathy and depression symptoms were associated with poorer functional performance in QD and apathy was associated with poorer functional performance in AD. In QD, subjects with apathy, depression, or coexistence of apathy and depression had poorer functional performance than those with neither apathy nor depression. The coexistence of apathy and depression did not produce more severe functional disability than apathy alone or depression alone. In AD, subjects with apathy had poorer functional performance than those without apathy. Depression in the absence of apathy was not associated with more severe functional disability. CONCLUSION: Apathy and depression symptoms are common in the early course of AD. Apathy and depression had different effects on functional performances in the subjects with QD from those with AD.     

SPECT findings in Alzheimer's disease and Parkinson's disease with dementia

We examined, with single photon emission tomography (SPECT) and (^99mTc)-HMPAO, 18 patients with idiopathic Parkinson's disease and no dementia (PD), 12 patients with PD and dementia, 24 patients with probable Alzheimer's disease (AD) and 14 controls. While the three patient groups showed significantly lower perfusion in frontal inferior and temporal inferior areas as compared to controls, both demented groups showed significantly more severe bilateral hypoperfusion in superior frontal, superior temporal and parietal areas as compared to non-demented PD patients and controls. On the other hand, no significant differences in cerebral perfusion were found between patients with AD and patients with PD and dementia. In conclusion, our findings demonstrated specific but similar cerebral perfusion deficits in demented patients with either AD or PD.     

Long-term safety and cognitive effects of galantamine in the treatment of probable vascular dementia or Alzheimer's disease with cerebrovascular disease.

The relationship between cholinergic dysfunction and cognitive and functional impairment in patients with vascular dementia (VaD) and Alzheimer's disease (AD) with cerebrovascular disease (CVD) suggests a potential role for cholinomimetic therapy. Initial studies of galantamine demonstrated cognitive, behavioral, and functional benefits in these populations. 326 patients with VaD or AD with CVD who completed an initial 12-month trial were treated with galantamine 24 mg/day in a 24-month, open-label extension. This interim analysis was performed at month 12 of the open-label extension (248 completed the trial). Galantamine (up to 24 months total) was well tolerated in both groups. The most frequently reported adverse events, characteristic of older dementia patients, included depression, agitation, and insomnia. Gastrointestinal adverse events were less common than initially, indicating declining incidence with long-term therapy. Patients taking galantamine for the entire study demonstrated the least cognitive decline on AD Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of galantamine were evident in both groups; cognitive baseline levels were maintained for approximately 21 months in VaD patients and for 12 months in patients with AD with CVD. Long-term (up to 24 months) galantamine therapy in patients with VaD and AD with CVD is well tolerated and associated with prolonged maintenance of cognitive function.     

Comparison of minaprine and placebo in the treatment of Alzheimer's disease and multi-infarct dementia

Minaprine, an aminopyridazine derivative, represents a new class of antidepressants; in addition minaprine has been shown to possess cholinomimetic properties in rodents. Thus it seemed of interest to study the efficacy and tolerance of minaprine in the treatment of depressed mood, behavioural impairment and cognitive deterioration of senile dementia. A total of 122 patients were included in this three-month, randomized, double-blind, placebo-controlled, multicentric trial; 63 patients suffered from senile dementia of Alzheimer's type (SDAT) and 59 from multi-infarct dementia (MID). In both SDAT and MID, minaprine (100 mg bid) was more effective than placebo in relieving depressed mood. In some MID patients, minaprine also improved behavioural impairment. In SDAT patients, minaprine seemed to improve some aspects of cognitive function, as judged by a limited battery of psychometric tests. Overall, minaprine appeared to be more effective in MID, although longer treatment and/or higher dosage may be necessary in SDAT. The incidence of side-effects was low in both treatment groups.     

Dehydroepiandrosterone sulfate (DHEA-S) and Alzheimer's dementia in older subjects

OBJECTIVES AND METHODS: We investigated the association of serum dehydroepiandrosterone sulfate (DHEA-S) levels with dementia of Alzheimer's type (DAT) and impairment in selected cognitive domains (memory, language, attention and working memory) in 158 patients (75.5+/-6.7 years, 46 men) with first-diagnosed probable DAT and in 158 age- and sex-matched controls. As secondary goal, we evaluated whether DHEA-S baseline levels were associated with cumulative 6-year mortality. RESULTS: A negative correlation between DHEA-S levels and age was observed (R=-0.25, p<0.001). Age-stratified analysis did not show significant differences of DHEA-S levels between DAT patients and controls. No significant association was found between DHEA-S levels and impairment in selected cognitive domains. Cox regression analysis showed that baseline DHEA-S levels were not associated with cumulative 6-year mortality. CONCLUSIONS: In a sample of newly-diagnosed DAT patients, we did not find significant association between presence of DAT or impairment in cognitive domains and DHEA-S levels; baseline DHEA-S levels are not associated with cumulative mortality in patients and controls.     

Recent advances in drug treatment for Alzheimer's dementia

The increasing ageing population and subsequent increase in dementia means that the need for finding appropriate treatments has become more important. Current treatments are limited and only provide some symptomatic improvements in patients. This article reviews the recent drug advances in treatment for Alzheimer's disease which have been of varying success. It appears that a combination of these will be required.     

Pathological diagnosis of combined Alzheimer's disease and argyrophilic grain dementia in a very elderly man who presented with advanced behavioural and psychological symptoms

This case report describes a Japanese man who presented with slowly progressive memory disturbances that began at the age of 79 years. The man also displayed conspicuous behaviour and psychological symptoms in the early stage of dementia. Computed tomography revealed atrophy of the amygdala and severe hippocampal deterioration, particularly in the anterior portion. Lateral ventricular dilatation, mainly affecting the anterior and inferior horns, was also observed. Interestingly, cerebral neocortical atrophy in the frontal and temporal lobes was considerably mild for the patient's age. Apolipoprotein E gene analysis showed epsilon 3 homozygosity. The patient died at the age of 96 years, and his clinical diagnosis was Alzheimer's disease with severe behavioural and psychological symptoms of dementia. In addition to indicating considerable hippocampal atrophy, an autopsy revealed numerous neurofibrillary tangles and argyrophilic grains in the brain, as well as extensive senile plaques. Cerebral amyloid angiopathy was also recognized. The pathological findings were suggestive of both Alzheimer's disease and argyrophilic grain dementia; other neurodegenerative disorders were not apparent. The clinicopathologic findings of the present case suggest significant consideration should be made when determining the clinical diagnosis and pathogenesis of senile dementia.