Progressive loss of expressive language in a journalist: What news for dementia?

A 77-year-old man with 8 year progressive language deterioration in the face of grossly intact memory was followed. No acute or chronic physiological or psychological event was associated with symptom onset. CT revealed small left basal ganglia infarct. Mild atrophy, no lacunar infarcts, mild diffuse periventricular changes registered on MRI. Gait normal but slow. Speech hesitant and sparse. Affect euthymic; neurobehavioral disturbance absent. MMSE 26/30; clock incorrect, concrete. Neuropsychological testing revealed simple attention intact; complex attention, processing speed impaired. Visuospatial copying and delayed recall of copy average with some perseveration. Apraxia absent. Recall mildly impaired. Mild deficits in planning, organization apparent. Patient severely aphasic, dysarthric without paraphasias. Repetition of automatic speech, recitation moderately impaired; prosody intact. Understanding of written language, nonverbal communication abilities, intact. Frontal release signs developed over last 12 months. Repeated cognitive testing revealed mild deterioration across all domains with significant further decrease in expressive, receptive language. Neurobehavioral changes remain absent to date; he remains interested, engaged and independent in basic ADLs. Speech completely deteriorated; gait and movements appreciably slowed. Although signs of frontal/executive dysfunction present, lack of behavioral abnormalities, psychiatric disturbance, personality change argue against focal or progressive frontal impairment or dementia. Relative intactness of memory and comprehension argue against Alzheimer’s disease. Lack of findings on neuroimaging argue against CVA or tumor. It is possible that the small basal ganglia infarct has resulted in a mild lateral prefrontal syndrome. However, the absence of depression as well as the relatively circumscribed language problem suggests otherwise. The progressive, severe nature of language impairments, with relatively minor impairments in attention and memory, argues for a possible diagnosis of primary progressive aphasia.

Plasma antioxidant status, immunoglobulin G oxidation and lipid peroxidation in demented patients:Relevance to Alzheimer disease and vascular dementia

A large body of evidence supports a role of oxidative stress in Alzheimer disease (AD) and in cerebrovascular disease. A vascular component might be critical in the pathophysiology of AD, but there is a substantial lack of data regarding the simultaneous behavior of peripheral antioxidants and biomarkers of oxidative stress in AD and vascular dementia (VaD). Sixty-three AD patients, 23 VaD patients and 55 controls were included in the study. We measured plasma levels of water-soluble (vitamin C and uric acid) and lipophilic (vitamin E, vitamin A, carotenoids including lutein, zeaxanthin, β-cryptoxanthin, lycopene, α- and β-carotene) antioxidant micronutrients as well as levels of biomarkers of lipid peroxidation [malondialdehyde (MDA)] and of protein oxidation [immunoglobulin G (IgG) levels of protein carbonyls and dityrosine] in patients and controls. With the exception of β-carotene, all antioxidants were lower in demented patients as compared to controls. Furthermore, AD patients showed a significantly higher IgG dityrosine content as compared to controls. AD and VaD patients showed similar plasma levels of plasma antioxidants and MDA as well as a similar IgG content of protein carbonyls and dityrosine. We conclude that, independent of its nature - vascular or degenerative - dementia is associated with the depletion of a large spectrum of antioxidant micronutrients and with increased protein oxidative modification. This might be relevant to the pathophysiology of dementing disorders, particularly in light of the recently suggested importance of the vascular component in AD development. Copyright © 2004 S. Karger AG, Basel.

P4-235 protein oxidation, lipid peroxidation and antioxidant status are similarly altered in Alzheimer disease and vascular dementia

Background: A large body of evidence supports a role of oxidative stress in Alzheimer disease (AD) and in cerebrovascular disease. A vascular component might be critical in the pathophysiology of AD. Objective(s): To evaluate the simultaneous behavior of a broad spectrum of peripheral antioxidants and biomarkers of oxidative stress in AD and vascular dementia (VaD). Methods: Sixty-three AD patients, 23 VaD patients and 55 controls were included in the study. We measured plasma levels of water-soluble (vitamin C and uric acid) and lipophilic (vitamin E, vitamin A, carotenoids including lutein, zeaxanthin, [3-cryptoxanthin, lycopene, c~- and [3-carotene) antioxidant micronutrients as well as levels of biomarkers of lipid peroxidation [malondialdehyde (MDA)] and of protein oxidation [immunoglobniin G (Ig G) levels of protein carbonyls and dityrosine] in patients and controls. Results: AD and VaD patients showed significantly decreased plasma levels of the water-soluble vitamin C and uric acid, of the lipophilic vitamin Eand vitamin A, and of the carotenoids lutein, zeaxanthin, 13-cryptoxanthin, lycopene and (x-carotene as compared to controls; among biomarkers of oxidative stress, only the content of dityrosine in Ig G was found to be significantly higher (p < 0.01) in AD patients as compared to controls; although a trend towards higher levels of dityrosine was also observed in VaD subjects compared to controls (6.3 4- 1.7 ~M in VaD patients vs. 5.1 4- 1.6 IxM in controls; p = 0.06), it did not reach statistical significance. In a cumulative analysis of all patient samples, a significant inverse association was found between plasma lycopene and MDA levels (r = -0.53, p < 0.0001). Conclusions: Independent of its nature-vascular or degenerativedementia is associated with the depletion of a large spectrum of antioxidant micronutrients and with increased protein oxidative modification. This might be relevant to the pathophysiology of dementing disorders, particularly in light of the recently suggested importance of the vascular component in AD development.

Reduced transferrin binding in Down syndrome:a route to senile plaque formation and dementia

Plasma transferrin binding in Down syndrome and Alzheimer's disease is significantly reduced compared with age matched controls and it was thought this may help elucidate a pathological time sequence for the onset of dementia in Down syndrome. In Down syndrome, there was a reduction in gallium and aluminium transferrin binding both with age and the onset of dementia. Non-transferrin bound gallium species were identified as non-transportable phosphate or silicate. Thus, the route of entry of metals into the brain must be via a transferrin mediated complex only. A clear sequence of pathological events has been demonstrated in Down syndrome which shows the pathway to development of plaques and dementia and this is believed to have an immunological origin.

Size frequency distribution of the β-amyloid (aβ) deposits in dementia with Lewy bodies with associated Alzheimer’s disease pathology

The objective is to study beta-amyloid (Abeta) deposition in dementia with Lewy bodies (DLB) with Alzheimer's disease (AD) pathology (DLB/AD). The size frequency distributions of the Abeta deposits were studied and fitted by log-normal and power-law models. Patients were ten clinically and pathologically diagnosed DLB/AD cases. Size distributions had a single peak and were positively skewed and similar to those described in AD and Down's syndrome. Size distributions had smaller means in DLB/AD than in AD. Log-normal and power-law models were fitted to the size distributions of the classic and diffuse deposits, respectively. Size distributions of Abeta deposits were similar in DLB/AD and AD. Size distributions of the diffuse deposits were fitted by a power-law model suggesting that aggregation/disaggregation of Abeta was the predominant factor, whereas the classic deposits were fitted by a log-normal distribution suggesting that surface diffusion was important in the pathogenesis of the classic deposits.

Laminar distribution of β-amyloid deposits in dementia with Lewy bodies and in Alzheimer's disease

This study tested whether the laminar distribution of the β-amyloid (Aβ) deposits in dementia with Lewy bodies (DLB) cases with significant Alzheimer's disease (AD) pathology (DLB/AD) was similar to "pure" AD. In DLB/AD, the maximum density of the diffuse and primitive deposits occurred either in the upper laminae or a bimodal distribution was present with density peaks in the upper and lower laminae. A bimodal distribution of the classic Aβ deposits was also observed. Compared with AD, DLB/AD cases had fewer primitive deposits relative to the diffuse and classic deposits; the primitive deposits exhibited a bimodal distribution more frequently, and the diffuse deposits occurred more often in the upper laminae. These results suggest that Aβ pathology in DLB/AD may not simply represent the presence of associated AD. © 2006 Sage Publications.

Beta-amyloid deposition in the temporal lobe of patients with dementia with Lewy bodies:Comparison with non-demented cases and Alzheimer's disease

β-Amyloid (Aβ) deposition in regions of the temporal lobe in patients with dementia with Lewy bodies (DLB) was compared with elderly, non-demented (ND) cases and with Alzheimer's disease (AD). The distribution, density and clustering patterns of diffuse, primitive and classic Aβ deposits were similar in 'pure' DLB and ND cases. The distribution of Aβ deposits and the densities of the diffuse and primitive deposits were similar in 'mixed' DLB/AD cases compared with AD. However, the density of the classic deposits was significantly lower in DLB/AD compared with AD. In addition, the primitive Aβ deposits occurred more often in small, regularly spaced clusters in the tissue and less often in a single large cluster in DLB/AD compared with 'pure' AD. These results suggest that pure DLB and AD are distinct disorders which can coexist in some patients. However, the Aβ pathology of DLB/AD cases is not identical to that observed in patients with AD alone. (C) 2000 S. Karger AG, Basel.

The impact of anticholinergic burden in Alzheimer's dementia-the LASER-AD study

Objective - to examine the effect of medications with anticholinergic effects on cognitive impairment and deterioration in Alzheimer's dementia (AD). Methods - cognitive function was measured at baseline and at 6- and 18-month follow-up using the Mini-Mental State Exam (MMSE), the Severe Impairment Battery (SIB) and the Alzheimer's Disease Assessment Battery, Cognitive subsection (ADAS-COG) in a cohort study of 224 participants with AD. Baseline anticholinergic Burden score (ABS) was measured using the Anticholinergic Burden scale and included all prescribed and over the counter medication. Results - the sample was 224 patients with Alzheimer's dementia and 71.4% were women. Their mean age was 81.0 years [SD 7.4 (range 55–98)]. The mean number of medications taken was 3.6 (SD 2.4) and the mean anticholinergic load was 1.1 (SD 1.4, range 0–7). The total number of drugs taken and anticholinergic load correlated (rho = 0.44; P < 0.01). There were no differences in MMSE and other cognitive functioning at either 6 or 18 months after adjusting for baseline cognitive function, age, gender and use of cholinesterase inhibitors between those with, and those without high anticholinergenic load. Conclusions - medications with anticholinergic effect in patients with AD were not found to effect deterioration in cognition over the subsequent 18 months. Our study did not support a continuing effect of these medications on people with AD who are established on them.

New networked technologies and carers of people with dementia: an interview study

Dementia is one of the greatest contemporary health and social care challenges, and novel approaches to the care of its sufferers are needed. New information and communication technologies (ICT) have the potential to assist those caring for people with dementia, through access to networked information and support, tracking and surveillance. This article reports the views about such new technologies of 34 carers of people with dementia. We also held a group discussion with nine carers for respondent validation. The carers' actual use of new ICT was limited, although they thought a gradual increase in the use of networked technology in dementia care was inevitable but would bypass some carers who saw themselves as too old. Carers expressed a general enthusiasm for the benefits of ICT, but usually not for themselves, and they identified several key challenges including: establishing an appropriate balance between, on the one hand, privacy and autonomy and, on the other: maximising safety; establishing responsibility for and ownership of the equipment and who bears the costs; the possibility that technological help would mean a loss of valued personal contact; and the possibility that technology would substitute for existing services rather than be complementary. For carers and dementia sufferers to be supported, the expanding use of these technologies should be accompanied by intensive debate of the associated issues.

Oxidative LDL modification is increased in vascular dementia and is inversely associated with cognitive performance

It is not known whether the association between increased plasma homocysteine (Hcy) associated with LDL modification and propensity for LDL uptake by macrophages in cardiovascular disease patients holds true in vascular dementia (VaD). Plasma from 83 subjects diagnosed with Alzheimer's disease (AD), VaD, mild cognitive impairment (MCI) and from controls was analysed to examine (1) whether LDL isolated from the plasma of VaD is biochemically and functionally distinct from that isolated from AD, MCI or controls; and (2) whether such biomarkers of LDL phenotype are related to plasma folate levels, Hcy levels and/or to disease severity. Folate and vitamin B6 levels were significantly lower in VaD subjects than in controls. VaD-LDL showed increased protein carbonyl content (p <0.05) and was more susceptible to scavenging by macrophages (p <0.05) than AD- or control-LDL. Patients from the VaD cohort were more prevalent in the lowest tertile for HDL:LDL and the upper tertile for LDL oxidation; the combined parameters of HDL cholesterol, LDL oxidation and scavenging by macrophages show 87% sensitivity towards VaD detection. The association between folate deficiency, LDL modification and dysfunction in VaD but not in AD may provide a novel biomarker assessment to discriminate between the diseases.

Clustering of neuronal inclusions in "dementia with neurofilament inclusions"

Dementia with neurofilament inclusions (DNI) is a new disorder characterized clinically by early-onset dementia and histologically by the presence of intraneural inclusions immunopositive for neurofilament antigens but lacking tau and α-synuclein reactivity. We studied the clustering patterns of the neurofilament inclusions (NI) in regions of the temporal lobe in three cases of DNI to determine whether they have the same spatial patterns as inclusions in the tauopathies and α-synucleinopathies. The NI exhibited a clustered distribution (mean size of clusters 400 μm, range 50-800 μm, SD 687.8) in 24/28 of the areas studied. In 22 of these areas, the clusters exhibited a regular distribution along the tissue parallel to the pia mater or alveus. In 3 cortical areas, there was evidence of a more complex pattern in which the NI clusters were aggregated into larger superclusters. In 6 cortical areas, the size of the clusters approximated to those of the cells of origin of the cortico-cortical pathways but in the remaining areas cluster size was smaller than 400 μm. Despite the unique molecular profile of the NI, their spatial patterns are similar to those shown by filamentous neuronal inclusions in the tauopathies and α-synucleinopathies.