Atrophy of the cholinergic basal forebrain in dementia with Lewy bodies and Alzheimer’s disease dementia

Similar to Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) is characterized by a profound degeneration of cortically-projecting cholinergic neurons of the basal forebrain (BF) and associated depletion of cortical cholinergic activity. We aimed to investigate subregional atrophy of the BF in DLB in vivo and compare it to the pattern of BF atrophy in AD. Structural MRI scans of 11 patients with DLB, 11 patients with Alzheimer’s disease, and 22 healthy controls were analysed using a recently developed technique for automated BF morphometry based on high-dimensional image warping and cytoarchitectonic maps of BF cholinergic nuclei. For comparison, hippocampus volume was assessed within the same morphometric framework using recently published consensus criteria for the definition of hippocampus outlines on MRI. The DLB group demonstrated pronounced and subregion-specific atrophy of the BF which was comparable to BF atrophy in AD: volume of the nucleus basalis Meynert was significantly reduced by 20–25 %, whereas rostral BF nuclei were only marginally affected. By contrast, hippocampus volume was markedly less affected in DLB compared to AD. Global cognition as determined by MMSE score was associated with BF volume in AD, but not in DLB, whereas visuoperceptual function as determined by the trail making test was associated with BF volume in DLB, but not in AD. DLB may be characterized by a more selective degeneration of the cholinergic BF compared to AD, which may be related to the differential cognitive profiles in both conditions.     

Association of estrogen receptor β gene polymorphisms with vascular dementia in women

The objective of the present study was to explore a potential association between the estrogen receptor β (ERβ) gene polymorphisms and vascular dementia (VaD) in women. The relationship of two polymorphisms (rs944050 and rs4986938) and their associated haplotypes in the ERβ gene with VaD were examined in 121 Chinese Han women (>50?years of age) including 61 with VaD and 60 healthy age-matched controls. The potential associations were evaluated using unconditional logistic regression. The variant allele G of rs944050 in the ERβ gene increased the risk of VaD (odds ratio?=?2.02, 95% confidence interval?=?1.08-3.77). In haplotype analyses, the ERβ haplotype containing the polymorphism rs944050 variant allele and the polymorphism rs4986938 wild-type allele was associated with VaD (odds ratio?=?1.70, 95% confidence interval?=?1.03-2.84). The polymorphism rs944050 in the ERβ gene was associated with an increased risk of VaD in Chinese Han women. Further studies regarding the association between the ERβ gene polymorphisms and VaD are needed to confirm these findings.     

Who participates in psychosocial interventions for caregivers of patients with dementia?

OBJECTIVE: The purpose of the present study is to evaluate if the participants in psychosocial interventions for dementia caregivers are representative of the whole population of dementia patients or if some socioeconomic groups are over- or underrepresented. DESIGN: The demographic and socioeconomic characteristics of the 128 participants of a randomized controlled study on the effects of caregiver education were compared with those of all the elderly residents of the City of Zurich (n = 64,856, elderly group), of all demented patients entering a City of Zurich nursing home in a 6-month period (n = 218, NH entry group) and of all demented inhabitants evaluated during a 20-month follow-up at a community memory clinic (n = 187, memory group). METHODS: Data on income and wealth were derived from official tax records. The characteristics of the different groups were compared by chi2 or t tests. RESULTS: As expected in a study on caregiver education, the demented patients were younger, more often male and married than all other study groups (p < 0.01). The participants in the psychosocial intervention had significantly (p < 0.01) higher education than all other groups; this effect is caused in part by the higher proportion of males. The NH entry group was less well educated than the elderly group (p < 0.05). The intervention group had a higher income and was wealthier than the three other groups (p < 0.01), but there was no significant difference with respect to the wealth of the memory group. The 25% poorest of the elderly group made up only about 10% of the participants in the intervention group. However, the 25% richest of the elderly group made up 42% of the intervention group. The method of recruitment for the psychosocial intervention (by media, referral of physicians and by a memory clinic) was not significantly related to any of the demographic or socioeconomic parameters. CONCLUSION: The lower socioeconomic strata are clearly underrepresented in psychosocial interventions.     

Is dementia reversible in patients with neurocysticercosis?

OBJECTIVE: To determine the correlates and outcome of dementia in patients with neurocysticercosis (NCC). METHODS: Ninety consecutive patients with untreated NCC underwent a cognitive assessment (Mini-mental State Examination, Neurobehavioral Cognitive Status Examination, and IQCODE) and were classified as having or not having dementia according to DSM-IV criteria. Imaging and cerebrospinal fluid examination data were recorded. The cognitive measures were repeated six months after treatment with albendazole and steroids. RESULTS: At the initial evaluation 15.5% (n = 14) of the patients were classified as having dementia. Dementia was associated with older age, lower education level, increased number of parasitic lesions in the brain (mostly in the frontal, temporal, and parietal lobes). After six months, 21.5% of the patients from the dementia group continued to have a full dementia disorder and 78.5% no longer fulfilled the DSM-IV criteria for dementia, although some of these patients still showed mild cognitive decline. CONCLUSIONS: The results of this study suggest that dementia occurs frequently in patients with untreated NCC, and it is reversible in most cases.     

Do people with dementia find lies and deception in dementia care acceptable?

Objectives: Research suggests that the use of lies and deception are prevalent in dementia care settings. This issue has been explored from the view point of carers and professionals, and the acceptability and ethicality of deception in dementia care remains an area of heated debate. This article explored the issue of lies and deception in dementia care from the unique perspective of the people being lied to: People with Dementia.

Method: This study used a qualitative methodology, specifically, Grounded Theory (GT). The study used a two-phased design. Phase one involved a series of one-to-one interviews with People with Dementia. During phase two, the participants were re-interviewed in order to develop the emerging theory.

Results: Lies were considered to be acceptable if told in People with Dementia's best interest. This best interest decision was complex, and influenced by factors such as the person with dementia's awareness of the lie, and the carer's motivation for lying. A model depicting these factors is discussed.

Conclusion: This study enables the perspective of People with Dementia to be considered, therefore providing a more complete understanding of the use of deceptive practices in dementia care settings. This study suggests that the use of lies and deception in dementia care warrants further investigation.     

Utility of the Mattis dementia rating scale to assess the efficacy of rivastigmine in dementia associated with Parkinson’s disease

INTRODUCTION: The severe, cortical, cholinergic depletion accompanying Parkinson's disease (PD) is considered as a highly probable correlate of cognitive and behavioural dysfunction. Recent studies have demonstrated that cholinesterase inhibitors (notably rivastigmine) are beneficial in patients suffering from dementia associated with PD (PDD). However, the primary efficacy variables used in such work came from scales designed for Alzheimer's disease (AD), even though the cognitive symptoms in PD and AD dementia do not overlap completely. The aim of the present study (a double-blind, placebo-controlled clinical trial) was to determine the utility of the Mattis dementia rating scale - the most commonly used scale in PD patients - to assess the efficacy of a 24-week rivastigmine treatment. METHODS: Twenty-eight patients with PD, who constituted a subgroup of patients enrolled to the EXPRESS study (Emre et al, N Engl J Med 2004) participated in this study. They suffered from mild to moderately severe dementia (MMSE scores above 10 and below 24), with an onset of cognitive symptoms occurring at least two years after the diagnosis of PD. Patients were randomly assigned to treatment with rivastigmine (3 to 12 mg per day) or placebo. The Mattis dementia rating scale was administered to patients from six centres in France at the baseline and end-point visits. RESULTS: Compared with placebo, a 24-week rivastigmine treatment led to a significant improvement in the overall score on the Mattis dementia rating scale (p = 0.031), with a trend towards a significant improvement in the "Attention" subscale score (p = 0.061). Correlation analysis showed that in the rivastigmine group, performance on the Mattis "Attention" and "Initiation" subscales appeared to contribute heavily to the improvement in the overall score. Moreover, the latter was also related to an improvement in activities of daily living and a reduction in behavioural disturbances. DISCUSSION: By using the Mattis dementia rating scale (which comprises items that are sensitive to executive dysfunction), the present study confirmed that rivastigmine has a beneficial effect on cognitive function in PDD. Despite our study's small sample size, the Mattis scale was able to detect this improvement and could thus be considered as an interesting outcome measure in further work.     

Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder?

OBJECTIVE: Several findings suggest that some patients with depressive or bipolar disorder may be at increased risk of developing dementia. The present study aimed to investigate whether the risk of developing dementia increases with the number of affective episodes in patients with depressive disorder and in patients with bipolar disorder. METHODS: This was a case register study including all hospital admissions with primary affective disorder in Denmark during 1970-99. The effect of the number of prior episodes leading to admission on the rate of readmission with a diagnosis of dementia following the first discharge after 1985 was estimated. A total of 18,726 patients with depressive disorder and 4248 patients with bipolar disorder were included in the study. RESULTS: The rate of a diagnosis of dementia on readmission was significantly related to the number of prior affective episodes leading to admission. On average, the rate of dementia tended to increase 13% with every episode leading to admission for patients with depressive disorder and 6% with every episode leading to admission for patients with bipolar disorder, when adjusted for differences in age and sex. CONCLUSION: On average, the risk of dementia seems to increase with the number of episodes in depressive and bipolar affective disorders.     

Is dementia with Lewy bodies the second most common cause of dementia?

Lewy bodies were originally described in isolated brainstem nuclei in persons with Parkinson's disease. They have since been recognized as a widespread and common neuropathologic finding in individuals with dementia. Dementia with Lewy bodies (DLB) is the preferred term for the dementia syndrome associated with Lewy bodies. Although DLB is acknowledged as the second most common degenerative dementia, trailing only Alzheimer's disease, its ranking with respect to vascular dementia remains controversial. Large, community-based studies of DLB with postmortem confirmation are lacking. Available data suggest that DLB is more common than pure vascular dementia but not more common than any vascular contribution to dementia.     

Clinical and biochemical correlates of insoluble α-synuclein in dementia with Lewy bodies

α-Synuclein is a major constituent of Lewy bodies, the fibrillar aggregates that form within neurons in Parkinson’s disease and dementia with Lewy bodies (DLB). Recent biochemical data show that α-synuclein accumulates in Parkinson’s disease in a detergent insoluble form. We now examine the relationship between detergent insoluble α-synuclein and the presence of Lewy bodies, clinical measures of dementia and biochemical parameters in a series of individuals with DLB. We found that Triton X-100 insoluble α-synuclein enriched nearly twofold in the temporal cortex of patients with DLB compared to age-matched controls. By contrast the total amount of α-synuclein protein was unchanged. Surprisingly, the degree of Triton X-100 insoluble α-synuclein did not correlate with either the duration of illness or the number of Lewy bodies counted using stereological methods from an adjacent block of tissue. However, the Triton X-100 soluble fraction of α-synuclein did correlate strongly with the expression of several heat shock proteins (HSPs) in DLB but not control cases, suggesting a coordinated HSP response in DLB neocortex.     

Demonstration of amyloid β-protein in a 32-year-old man with progressive dementia

Summary We report the immunolocalization of extensive amyloid -protein in senile plaques, cerebrovascular amyloid deposits, neurofibrillary tangles and preamyloid in a 32-year-old man with progressive dementia not to trisomy 21 or trauma. These amyloid deposits were non-reactive to antibodies directed against scrapie amyloid. Our data indicate that the presence of amyloid -protein is not limited to normal aging, Alzheimer's disease and related disorders but is also found in younger individuals with progressive dementia.     

Association of apolipoprotein ɛ4 allele and neuropathologic findings in patients with dementia

Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE 4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE 4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.     

Brain perfusion effects of cholinesterase inhibitors in Parkinson’s disease with dementia

Summary. Several evidences suggest that cholinergic deficits may significantly contribute to dementia in Parkinson’s disease (PDD) and acetylcholinesterase inhibitors (ChEIs) have been reported to improve cognitive symptoms in PDD, without worsening parkinsonism. Nineteen PDD patients underwent brain perfusion SPECT with ^99mTc-ethyl cysteinate dimer after 6 months ChEIs treatment in order to evaluate the functional correlates of clinical improvement. A clear-cut cognitive improvement was reported in PDD patients with a significant improvement of ADAS-cog total score as well as of subscores exploring executive functions (p < 0.01). MMSE total score did not significantly change after ChEIs but the subscore of attention significantly improved after therapy (p < 0.01). No difference in motor performance as evaluated by UPDRS was reported. SPM analysis showed a significant increase of perfusion (p < 0.0001) in bilateral cingulate, and frontal regions after ChEIs. Our data confirm the efficacy of ChEIs in the treatment of dementia associated with PD mainly on attention and executive functions, and the functional findings indicate that this cognitive improvement could be associated with a sort of pharmacological frontal “re-afferentation”.     

Cerebrospinal fluid markers analysis in the differential diagnosis of dementia with Lewy bodies and Parkinson’s disease dementia

European Archives of Psychiatry and Clinical Neuroscience - Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) share a couple of clinical similarities that is often a...     

Assessment of sleep satisfaction in patients with dementia due to Alzheimer’s disease

Sleep length and architecture are potential markers of progressive cognitive impairment, while neuropsychiatric symptoms and APOE4− haplotypes have been associated with more sleep complaints in patients with dementia due to Alzheimer’s disease (AD). In this cross-sectional study, we sought to investigate which factors might be related to sleep satisfaction in patients with AD. A total of 217 consecutive patients with AD were assessed for demographic features, neuropsychiatric symptoms, cognitive decline, functional impairment for activities of daily living, caregiver burden, APOE haplotypes, self-reported sleep satisfaction and length of sleep. Statistical comparisons were conducted with significance at p < 0.05. Concerning sleep complaints, 179 patients (82.5%) reported satisfactory sleep, while 38 (17.5%) were unsatisfied, with no relation to age, sex, APOE haplotypes, obesity, education, marital status, alcohol consumption or smoking found. Length of sleep (p = 0.011) and behavioural symptoms (p = 0.009) had significant associations with sleep satisfaction. Length of sleep was positively correlated with apathy (p = 0.014) and scores on the Clock Drawing Test (p = 0.015), and inversely correlated with anxiety (p = 0.015) and independence for instrumental activities of daily living (p = 0.003). Patients who were treated with memantine (p = 0.02) or anti-psychotics (p < 0.01) had longer duration of sleep. In conclusion, behavioural symptoms had strong associations with sleep satisfaction, which is highly correlated with length of sleep in patients with AD. Functional independence, apathy, anxiety, use of memantine or anti-psychotics, and scores on the Clock Drawing Test were significantly associated with length of sleep in this sample.     

Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer’s disease, and dementia with Lewy bodies

The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer’s disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic–ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD.     

A quantitative study of α-synuclein pathology in fifteen cases of dementia associated with Parkinson disease

The α-synuclein-immunoreactive pathology of dementia associated with Parkinson disease (DPD) comprises Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG). The densities of LB, LN, LG together with vacuoles, neurons, abnormally enlarged neurons (EN), and glial cell nuclei were measured in fifteen cases of DPD. Densities of LN and LG were up to 19 and 70 times those of LB, respectively, depending on region. Densities were significantly greater in amygdala, entorhinal cortex (EC), and sectors CA2/CA3 of the hippocampus, whereas middle frontal gyrus, sector CA1, and dentate gyrus were least affected. Low densities of vacuoles and EN were recorded in most regions. There were differences in the numerical density of neurons between regions, but no statistical difference between patients and controls. In the cortex, the density of LB and vacuoles was similar in upper and lower laminae, while the densities of LN and LG were greater in upper cortex. The densities of LB, LN, and LG were positively correlated. Principal components analysis suggested that DPD cases were heterogeneous with pathology primarily affecting either hippocampus or cortex. The data suggest in DPD: (1) ratio of LN and LG to LB varies between regions, (2) low densities of vacuoles and EN are present in most brain regions, (3) degeneration occurs across cortical laminae, upper laminae being particularly affected, (4) LB, LN and LG may represent degeneration of the same neurons, and (5) disease heterogeneity may result from variation in anatomical pathway affected by cell-to-cell transfer of α-synuclein.     

Follow-up investigations in cerebrospinal fluid of patients with dementia with Lewy bodies and Alzheimer’s disease

Summary. Measuring proteins in cerebrospinal fluid (CSF) has gained wide acceptance for the differential diagnosis of dementia. Some groups have already extended these investigations in Alzheimers disease (AD) by asking how stable these markers are in follow-up analysis, if they depend on the stage of disease and whether they can be used to monitor the progression and biological effects of treatment. We evaluated 21 patients with dementia with Lewy bodies (DLB) and 19 patients with AD, on two occasions, with regard to levels of tau protein, tau protein phosphorylated at threonine 181 (p-tau), A42, A40 and S-100B protein, using a set of commercially available assays.Tau protein levels were lower in DLB in first and second LP compared to AD and decreased during course of both groups. P-tau levels were increased in AD and DLB and decreased during follow-up. A42 and A40 remained relatively stable during follow-up but we found a slight increase of the median A42 level in DLB, whereas in AD, A42 tends to decrease during follow-up. S-100B protein increased during follow-up in both diseases.The protein dynamics in DLB and AD are relatively similar. S-100B protein may be a useful marker for follow-up in neurodegenerative diseases but has to be analysed in longer follow-up periods. Tau protein may be used to differentiate between DLB and AD.Follow-up CSF analyses are of limited value for the differentiation of AD and DLB. We conclude that more specific markers have to be established for the differentiation and follow-up of these diseases.