Showing papers in "Dementia and Geriatric Cognitive Disorders in 2001"
TL;DR: A visuo-spatial associative learning test accurately distinguished AD from depressed/control subjects and revealed an apparent sub-group of QD patients who performed like AD patients, correlated with the degree of subsequent global cognitive decline.
Abstract: The development of novel treatments for Alzheimer’s disease (AD), aimed at ameliorating symptoms and modifying disease processes, increases the need for early diagnosis. Neuropsychological deficits su
363 citations
TL;DR: The modified Jadad scale appears to be a useful tool for AD research because of the very good interrater reliability and it is composed of items that are well suited to the specific disease characteristics of AD.
Abstract: Drug therapies for Alzheimer's disease (AD) have been evaluated in clinical trials over the past 2 decades. Systematic reviews of AD drug trials can shed more light on the efficacy of pharmaceutical interventions. The modified Jadad scale can be used to assess the quality of trial reports that are candidates for inclusion in these systematic reviews. The interrater reliability of the modified Jadad scale was examined during such a review. Three blinded reviewers rated the quality of 42 AD drug trial reports: the intraclass correlation coefficient was 0.90. The modified Jadad scale appears to be a useful tool for AD research because of the very good interrater reliability. Also, it is composed of items that are well suited to the specific disease characteristics of AD. Further research should focus on the validity of this instrument.
318 citations
TL;DR: An inverse association between blood pressure and dementia risk in elderly persons on antihypertensive medication is suggested, suggesting they may need higher blood pressure levels to maintain an adequate cerebral perfusion or lower blood pressure may be secondary to brain lesions in preclinical stages of dementia.
Abstract: The association between blood pressure and dementia is debated. Results from population-based studies on blood pressure and dementia are inconclusive, and most are performed in subjects younger than 8
266 citations
TL;DR: Fasting total serum homocysteine appears to be an independent predictor of cognitive decline in healthy elderly and exerts a maximal effect on spatial copying skills.
Abstract: Serum homocysteine is increased, and correlates inversely with cognitive scores, in Alzheimer’s disease (AD), vascular dementia and ‘age-associated memory impairment’. Elevated levels might signal acc
220 citations
TL;DR: Clinical ratings showed slight improvement after 3 weeks treatment with clioquinol in this open study, which may indicate a temporary cytotoxicity to the brain and/or an increased release into the CSF from stores in the tissue, possibly from senile plaques where the proteins are accumulated.
Abstract: As heavy metal ions may be implicated in the formation of senile plaques in Alzheimer-afflicted brains, treatment with clioquinol was tested in 20 patients with Alzheimer's disease. Clioquinol is a chelator that crosses the blood-brain barrier and has greater affinity for zinc and copper ions than for calcium and magnesium ions. Treatment was given for 21 days at doses of 20 mg/day to 10 patients and 80 mg/day to another 10 patients. The study was blind to the dosages but included no controls. Cerebrospinal fluid (CSF) investigations revealed a significant increase at day 7 and a decrease at day 21 in Tau protein and growth-associated protein (GAP43). These proteins are increased in Alzheimer's disease and considered as rather stable markers. The initial increase may indicate a temporary cytotoxicity to the brain and/or an increased release into the CSF from stores in the tissue, possibly from senile plaques where the proteins are accumulated. The levels of CSF-Tau protein correlated positively and significantly with the serum levels of copper and also with the serum copper/zinc ratio. Clinical ratings showed slight improvement after 3 weeks treatment with clioquinol in this open study.
215 citations
TL;DR: It is shown that the afferent limb of the leptin feedback loop is intact in below-appropriate-weight AD patients and suggest hypothalamic dysfunction may underlie this feature, and inappropriately elevated leptin levels do not appear to be implicated.
Abstract: Weight loss is common in Alzheimer’s disease (AD) and is predictive of mortality. Leptin, an adipocyte-derived peptide hormone is implicated in the regulation of satiety and energy expenditure. It act
148 citations
TL;DR: This study, utilizing concurrent, nonrandomized controls, suggests that donepezil continues to have efficacy over at least the first year of therapy and whether the benefits are maintained beyond 1 year is needed.
Abstract: Objective: To compare rates of cognitive decline between probable Alzheimer’s disease (AD) patients treated with long-duration cholinesterase inhibitors (ChE-Is) and those who remai
118 citations
TL;DR: In the identification of subjects with clinically manifest dementia symptoms (GDS stages 4 and 5), the B-ADL proved to be as efficient as the MMSE in the UK and German samples and superior to the MM SE in the Spanish sample.
Abstract: The Bayer-Activities of Daily Living Scale (B-ADL) is a 25-item, informant-rated questionnaire which was developed as a brief and internationally applicable instrument for assessing functional disabil
107 citations
TL;DR: Positive and highly significant correlations were found betweenCSF-tau and CSF-GAP-43 in all groups and between CSF -tau, CSf-Gap-43 and CSFsAPP in AD, which may reflect a common pathophysiologic process such as axonal degeneration.
Abstract: Cerebrospinal fluid (CSF) levels of tau (total tau), growth-associated protein-43 (GAP-43), soluble amyloid precursor protein (sAPP; i.e. total sAPP), and beta-amyloid(42) (Abeta(42)) were studied in patients with frontotemporal dementia (FTD; n = 14), Alzheimer's disease (AD; n = 47) and vascular dementia (VAD; n = 16), and in age-matched controls (n = 12). CSF-tau was increased in AD compared to controls and FTD (p < 0.001 for both). CSF-GAP-43 was increased in AD compared to controls (p < 0.05), and both CSF-GAP-43 and CSF-sAPP were increased in AD compared to FTD (p < 0.01). Positive and highly significant correlations were found between CSF-tau and CSF-GAP-43 in all groups and between CSF-tau, CSF-GAP-43 and CSF-sAPP in AD. The correlations found may reflect a common pathophysiologic process such as axonal degeneration.
103 citations
TL;DR: Subjects with DLB and AD have a different pattern of temporal lobe atrophy with the most striking differences relating to medial rather than lateral temporal lobe structures, which could explain the relative preservation of memory function in DLB compared to AD.
Abstract: Objectives: To compare medial and lateral temporal lobe atrophy on magnetic resonance imaging (MRI) in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD), and to examine t
100 citations
TL;DR: The structural cerebellar changes in the AD cases were neuronal loss, atrophy and gliosis, judged to represent the disease process, and with a main involvement in the vermis, with some of the symptoms and signs seen in AD being of noncerebellar origin.
Abstract: Structural manifestations of Alzheimer's disease (AD) including neuronal loss were investigated in 12 cases of AD and in 10 healthy age-matched controls, with focus on the cerebellum. Linear Purkinje cell (PC) density was measured in the vermis and cerebellar hemispheres. Neurons were also counted in the inferior olivary nucleus. In vermis of the AD cases, the mean PC number was significantly lower (p = 0.019) than in the controls. The neurons in the inferior olive were similarly fewer, though not significantly (p = 0.13). Molecular layer gliosis and atrophy in the vermis was clearly severer in AD than in the controls. Features typical of cerebral Alzheimer encephalopathy (plaques, tangles and microvacuolization) were inconspicious. The structural cerebellar changes in the AD cases were thus neuronal loss, atrophy and gliosis, judged to represent the disease process, and with a main involvement in the vermis. This may be reflected in some of the symptoms and signs seen in AD, signs that are generally overlooked or judged to be of noncerebellar origin.
TL;DR: The data confirm a strong association between Ε4 homozygotes and age at onset of AD but do not support an effect of Ε 4 allele copy number on rate of cognitive and functional decline nor on the efficacy of galantamine in patients with AD.
Abstract: Apolipoprotein E (APOE) has been extensively demonstrated to be a genetic risk factor for Alzheimer’s disease (AD). Associations of APOE genotype have been reported with age at AD onset, rate of decline, and responsiveness to therapy. This study aimed to test these hypotheses in a large study population of AD patients. APOE genotype was determined from 1,528 Caucasian subjects, diagnosed by NINCDS/ADRDA criteria as probable AD patients, enrolled in four international placebo-controlled clinical trials of 3–12 months duration, designed to evaluate efficacy of treatment with galantamine or sabeluzole. In addition to patient demographics and baseline scores for Mini Mental State Examination, scores on the Disability Assessment for Dementia (DAD) and the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) were recorded at the start, during, and at the end of the study. APOE E4 homozygotes had a significantly lower age at disease onset compared to patients with other APOE genotypes. The E4 allele was significantly over-represented in females compared to males, and in the group of subjects with an AD family history. Based on longitudinal data of 504 placebo-treated AD patients, the linear annual rate of change in score was 5 points on the ADAS-cog scale and 11 on the DAD scale. The E4 allele copy number did not influence these rates of decline. Sabeluzole treatment was not effective in the overall group compared to the placebo-treated group, nor in any subgroup stratified by E4 allele count. Galantamine produced cognitive and functional improvement that were not affected by E4 allele count. In conclusion, our data confirm a strong association between E4 homozygotes and age at onset of AD but do not support an effect of E4 allele copy number on rate of cognitive and functional decline nor on the efficacy of galantamine in patients with AD.
TL;DR: DLB patients without parkinsonism showed a significant reduction of occipital glucose metabolism which is comparable with that of DLB patients with parkinsonists, and the neurobiological bases of Occipital hypometabolism in DLB may be pathological processes in the brainstem or basal forebrain structures other than the nigrostriatal system.
Abstract: Reduction of glucose metabolism in the occipital lobe is reported in dementia with Lewy bodies (DLB) and Parkinson’s disease. If dysfunction of the nigrostriatal system is responsible for occipital hy
TL;DR: The present study identified single-dose responders in terms of improved attentional performance associated with a relatively higher alpha/theta activity in the right frontal regions of the brain measured on EEG and predominance of APOE Ε4 allele.
Abstract: A proportion of Alzheimer’s disease (AD) patients treated for several months with cholinesterase (ChE) inhibitors have shown some favorable response on cognition, but the characteristics of the respon
TL;DR: The results suggested that the left inferior temporal lobe contributes to verbal semantic memory, even after controlling for the effects of age, sex and educational attainment.
Abstract: We examined 57 patients with mild Alzheimer’s disease by using three kinds of verbal semantic memory tests (category fluency, confrontation naming and generation of verbal definition) and correlated each score with regional cerebral glucose metabolism determined by 18F-fluorodeoxyglucose and positron emission tomography. The scores of all three verbal semantic memory tests correlated significantly with regional cerebral glucose metabolism in the left inferior temporal gyrus, even after controlling for the effects of age, sex and educational attainment. In contrast, the scores of the word recall test did not correlate significantly with regional cerebral glucose metaboliosm in the left inferior temporal gyrus, neither before nor after controlling for these confounders. Our results suggested that the left inferior temporal lobe contributes to verbal semantic memory.
TL;DR: The reliability, validity and sensitivity of the most recent version of the Gottfries-Bråne-Steen GBS scale since its original publication in 1982 are described.
Abstract: Neuropsychological investigation using a comprehensive rating scale is important for the diagnosis and evaluation of dementia patients over time. Requirements for such a scale include accuracy, reliability, sensitivity of the scale over the disease course and simplicity for clinical use by a wide range of healthcare professionals. Ideally, the scale should also be capable of assessing the impact of pharmacological and non-pharmacological treatment regimens on the management of dementia patients. The Gottfries-Brane-Steen (GBS) Scale is a comprehensive global assessment tool for evaluating dementia symptoms and is based on a semi-structured interview and observation of the patient. The scale consists of subscales measuring intellectual (12 items), emotional (3 items) and activities of daily living, primarily items of self-care (6 items); as well as 6 items of behavioral and psychological symptoms of dementia. This review describes the reliability, validity and sensitivity of the most recent version of the GBS scale since its original publication in 1982.
TL;DR: The anatomical distribution of the neuronal calcium sensor proteins visinin-like protein-1 and -3 (VILIP-1) was investigated in various neocortical areas of Alzheimer's disease (AD) patients and controls as discussed by the authors.
Abstract: The anatomical distribution of the neuronal calcium sensor proteins visinin-like protein-1 and -3 (VILIP-1 and -3) was investigated in various neocortical areas of Alzheimer’s disease (AD) patients and controls. In AD and normal brains their cellular localization was confined to pyramidal and non-pyramidal neurons. In AD brains the intracellular immunostaining for VILIP-1 and to a lesser extent for VILIP-3 was found to be reduced in comparison to controls. Also, significantly less VILIP-1-immunoreactive neurons were found in the temporal cortex of AD patients as compared to normal brains. Accordingly, Western blot analysis revealed that immunoreactivity for VILIP-1 is less concentrated in tissue extracts of the temporal cortex of AD patients compared to controls. Extracellularly, VILIP-1 and VILIP-3 immunoreactive material was detected in close association with typical pathologic hallmarks of AD such as dystrophic nerve cell processes, amorphous and neuritic plaques, and extracellular tangles. In control brains an extraneuronal localization of VILIP-1 or VILIP-3 was never observed. Our morphological and neurochemical findings point to an involvement of these two neuronal calcium sensor proteins in pathology and possibly pathophysiology of changed calcium homeostasis in AD.
TL;DR: The lipid-AD associations in a very old cohort, and prior evidence that elevated TC in middle life is a risk factor for later dementia, prompt consideration of factors associated with lipid metabolism in the development of Alzheimer’s dementia.
Abstract: The relationships of serum lipids with Alzheimer’s disease (AD) and other dementias in very old patients are not clear. All residents of an academic nursing home were studied clinically for dementia a
TL;DR: A consistent pattern of synapse loss in the superior laminae of the frontal cortical area 10 of Brodman in heavy drinkers, not related to liver disease or possible previous mental disease, seems to be a plausible main cause of the alcoholic frontal symptomatology and alcoholic dementia.
Abstract: Alcoholics often develop personality and behavioural changes, social and personal neglect, confabulation, lack of insight, empathy and emotional control. Such symptoms would increase the risk of engagement in and exposure to acts of violence and criminal activities carrying a risk of physical damage including head trauma and violent death. This was the case in at least 4 of the studied cases. A structural basis for such frontal lobe symptoms was looked for in a forensic material of 18 alcoholics, compared with an age-matched control group with regard to liver disease, brain changes of the Wernicke-Korsakoff type and cortical, especially frontal cortical changes. The salient finding was a consistent pattern of synapse loss in the superior laminae of the frontal cortical area 10 of Brodman in heavy drinkers, not related to liver disease or possible previous mental disease. The synapse loss is more likely related to alcohol, possibly mediated through vitamin B deficiency. Brain stem lesions as a source of additional symptoms cannot be dismissed. This pattern of synapse loss in alcoholism has not been described previously. The cortical changes are closely similar to those found in frontotemporal dementia, and seem to be a plausible main cause of the alcoholic frontal symptomatology and alcoholic dementia.
TL;DR: 36 individuals who were initially diagnosed as having the memory-impaired primary degenerative type of MCI and therefore at high risk of developing Alzheimer’s disease are being followed up.
Abstract: Mild cognitive impairment (MCI) is a heterogeneous clinical syndrome for which no international diagnostic criteria have yet been established. Longitudinal studies have shown that many individuals who later develop dementia pass through a stage of MCI. We are following up 36 individuals who were initially diagnosed as having the memory-impaired primary degenerative type of MCI and therefore are at high risk of developing Alzheimer's disease. Clinical, neuropsychological, brain imaging and CSF biochemical markers were examined. Findings were remarkably heterogeneous even in this highly selected group of patients. This suggests that MCI is aetiologically not uniform.
TL;DR: Evidence is provided for several deranged synaptosomal proteins in several brain regions at the protein level indicating deficient synaptic wiring of the brain in Down syndrome and Alzheimer’s disease.
Abstract: Although it is well-known that synaptosomal proteins are deranged in neurodegenerative disorders, no information is available at the protein-chemical level as mainly immunochemical or immunohistochemical data were reported previously. We therefore investigated synaptosomal proteins in brain specimens from patients with Down syndrome (DS) and Alzheimer’s disease (AD) to challenge the DS synaptic pathology as well as the relevance of DS to AD in synaptic pathology. For the aim of this study, we employed two-dimensional electrophoresis and matrix-associated laser desorption ionization mass spectroscopy and determined β-soluble N-ethylmaleimide-sensitive factor attachment protein (β-SNAP), γ-SNAP and synaptotagmin I (SYT I) in 7 individual brain regions of controls and patients with DS and AD. In DS brain, β-SNAP was significantly reduced in temporal cortex (p
TL;DR: Quality of life can be measured in patients with dementia, but special tools need to be developed for severe dementia.
Abstract: Objective: The study was designed to determine the acceptability, feasibility and validity of measuring quality of life in a representative sample of dementia patients with a generi
TL;DR: The higher level of apolipoprotein E mRNA in AD with apoE Ε4 may play an important role in the development of AD and the result did not indicate the possibility that the promoter polymorphisms modulate the APoE mRNA level.
Abstract: In order to study progressive dementia in Alzheimer’s disease (AD) patients, we analyzed the gene expression of apolipoprotein E (apoE). ApoE mRNA level in the brains of patients with AD was determined by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. ApoE genotype and the promoter polymorphisms (–491A/T, Th1/E47cs) were determined by the PCR restriction fragment length polymorphism method. The apoE mRNA level was significantly higher in the AD group than the control group (p
TL;DR: Increased OS might play a crucial role in the rapid progression of Swedish FAD from the associative temporal cortex to the primary cerebrocortical areas.
Abstract: To evaluate the level of oxidative stress (OS) in familial Alzheimer’s disease (FAD), we analysed four cerebrocortical areas from patients with Swedish FAD bearing the APP670/671 mutation. The tempora
TL;DR: The hypothesis that AD is characterized by an alteration in pain experience is supported, i.e. compared to elderly persons without dementia, AD patients appear to perceive less pain intensity and pain affect.
Abstract: In previous studies, patients with probable Alzheimer’s disease (AD) have indicated that they experienced less pain intensity and affect from their painful conditions than nondemented elderly persons.
TL;DR: The relationships between the three-dimensional distribution of the scores and the DSM-IIIR grade of dementia indicated the existence of a continuum of dementia severity.
Abstract: A cognitive test comprising 27 subscales was administered to 262 demented patients and 92 normal subjects. Principal factor analysis followed by varimax and Harris-Kaiser rotation and Guttman’s scalog
TL;DR: An age-dependent increase in CSF tau in healthy individuals is found which might be caused by neuronal loss during normal ageing and redistribution of soluble tau from the brain into CSF.
Abstract: Cerebrospinal fluid (CSF) tau is a promising biochemical ante-mortem marker for Alzheimer’s disease (AD). Levels are increased in AD compared to other dementias, neurological diseases and healthy cont
TL;DR: This study demonstrates a decreased production of the anti-inflammatory compound IL-1ra, suggesting a propensity towards inflammation in patients with AD.
Abstract: A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of brain damage in dementia. In previous studies, we have demonstrated intrathecal production of the proinflammatory cytokine tumor necrosis factor (TNF)alpha in patients with Alzheimer's disease (AD). The aim of the present study was to investigate the downstream products of TNF-alpha expression including interleukin (IL)1beta and its naturally occurring antagonist IL-1 receptor agonist (ra) in patients with AD. The cytokine levels were related to neuronal damage, as measured by intrathecal tau and beta-amyloid concentration and certain clinical features of the disease. Fifty-two patients with AD and 25 healthy controls were analyzed with respect to cerebrospinal fluid (CSF) levels of IL-1beta and IL-1ra. CSF IL-1beta was neither detectable in CSF of AD nor in control CSF. In contrast, a significantly lower (p < 0.01) number of patients (24 of 49) than of controls (20 of 24) showed detectable levels of IL-1ra in the CSF. The intrathecal levels of IL-1ra were significantly lower in patients with AD than in the controls. Our study demonstrates a decreased production of the anti-inflammatory compound IL-1ra, suggesting a propensity towards inflammation in patients with AD.
TL;DR: The Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as mentioned in this paper.
Abstract: The Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). To investigate the genetic contribution of Notch mutations in familial cases with vascular leukoencephalopathy, we screened 13 patients from 11 unrelated families, which were selected on the basis of magnetic resonance imaging findings and positive family history. We identified three different missense mutations in 5 patients from 4 families. Two (Arg90Cys and Arg133Cys) are the same as previously reported in Caucasian patients, the other (Cys174Phe) is a novel mutation causing a loss of a cysteine in epidermal-growth-factor-like repeats of Notch3. These data indicate that the CADASIL Notch3 mutations were found in approximately 35% of familial cases with leukoencephalopathy, suggesting genetic heterogeneity of the disease.
TL;DR: Tau mutations were not found in subjects with a negative family history suggesting that tau mutations do not account for most sporadic cases of FTD, and no association of apolipoprotein E4 allele with FTD is found.
Abstract: We screened for tau gene mutations among 24 Japanese (6 familial and 18 sporadic cases) and 4 Polish patients with frontotemporal dementia (FTD) using PCR-SSCP analysis followed by DNA sequencing. We