Association between a PS-1 intronic polymorphism and late onset Alzheimer's disease

Previous work suggests an association between allele 1 and the 1-1 genotype of an intronic polymorphism in the presenilin-1 (PS-1) gene and late onset Alzheimer's disease. We found an excess of the 1-1 genotype in our late onset clinical sample (p = 0.006, one-tailed) but not in our postmortem confirmed sample, which instead exhibited an excess of allele 1 (p = 0.02, one-tailed). No interaction between PS-1 and ApoE genotype was detected and the findings remained significant when the effects of ApoE were taken into account (p = 0.03, one-tailed). These results suggest that the PS-1 polymorphism, or a locus in linkage disequilibrium with it, acts as a risk factor for late onset AD.     

Essential binding and functional domains of human bleomycin hydrolase

Bleomycin hydrolase (BH) is unusual among cysteine proteinases because it appears to form multihomomeric structures, inactivates the antitumor glycopeptide bleomycin, and contains a unique C-terminal amino acid sequence. We now demonstrate intrinsic endopeptidase activity associated with human BH (hBH) using artificial substrates and intracellular dimerization of hBH using a yeast two-hybrid assay. To determine domains important for homomeric interactions and catalysis, we constructed N- and C-terminal deletion mutants and identified an N-terminal region (hBH1-82) that interacted with two nonoverlaping hBH domains: one near the N-terminus (hBH14-103) and another neighboring the C-terminus (hBH358-455). In vitro hBH aggregated with a molecular mass of 235 kD corresponding to a homotetramer and the C-terminus was critical for this oligomerization since no tetramers were found when the last 40 amino acids were deleted. The penultimate 8 amino acids, which constitute a unique and highly conserved bleomycin hydrolase-like domain (BHYD), were essential for BH and aminopeptidase activity but not for endopeptidase activity or oligomer formation. Thus, the C-terminus of hBH has two independent roles controlling both the catalytic activity and oligomerization of hBH.     

Comparison between oral and written spelling in Alzheimer's disease

Written and oral spelling were compared in 33 patients with Alzheimer's disease (AD) and 25 control subjects. AD patients had poorer spelling results which were influenced by orthographic difficulty and word frequency, but not by grammatical word class. Lexical spelling was also more deteriorated than phonological spelling. Moreover, oral spelling was more impaired than written spelling in AD patients, whereas no difference was present between oral and written spelling of controls. Analysis of spelling errors showed that, for controls, errors were predominantly phonologically accurate in both spelling tasks. Significantly, AD patients produced more phonologically accurate than inaccurate errors in written spelling, whereas these errors did not differ in oral spelling. In contrast to controls who produced more constant than variable responses in oral and written spelling, AD patients made more variable responses (words correctly spelled in one task but incorrectly in the other) and they showed many instances of variable errors (different misspellings from one spelling task to the other). Two stepwise regression procedures showed that written misspellings were specifically correlated with language impairment, whereas oral spelling errors were correlated with attentional and language disorders. These results suggest that AD increases the attentional demands of oral spelling process as compared to written spelling. This dissociation argues, either for a unique Graphemic Buffer in which oral spelling requires more attentional resources than written spelling or for the hypothesis of separate buffers for oral and written spelling.     

Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia

OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimer's disease; patients with Alzheimer's disease showed more severe anosognosia and disinhibition than patients with Parkinson's disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinson's disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimer's disease. CONCLUSION: There were significant psychiatric differences between patients with Alzheimer's disease and demented patients with Parkinson's disease, but neuropsychological differences were restricted to a single cognitive domain.     

The link between Down's syndrome and Alzheimer's disease: 2

In this article, the second of two parts, the needs of family and professional carers of people with Down's syndrome and Alzheimer's disease are examined. Substantial numbers of people with Down's syndrome survive to the age of 50 and beyond and so work still needs to be done on finding solutions to the problems faced by this client group and its carers. As well as the difficulties faced by any family carer of a person with dementia, those caring for someone with Down's syndrome and Alzheimer's disease may also have to deal with additional worries and problems. Consideration is given to service provision and the implications for nursing. A case study will illustrate some of the points made.     

The relationship between psychiatric symptoms and regional cortical metabolism in Alzheimer's disease

Cognitive and noncognitive psychiatric symptoms were systematically evaluated in 21 patients with Alzheimer's disease by using the Neurobehavioral Rating Scale. Regional cerebral metabolic activity was measured in each patient by [18F]fluorodeoxyglucose PET. Significant correlations emerged between global cortical metabolic activity and the Agitation/Disinhibition factor score, Cognition factor score, and total score. Relationships between noncognitive symptoms and metabolic activity were regionally specific, with significant correlations between Agitation/Disinhibition factor score and metabolism in the frontal and temporal lobes, between Psychosis factor score and metabolism in the frontal lobe, and between Anxiety/Depression factor score and metabolism in the parietal lobe. These results suggest that psychiatric symptoms are fundamental expressions of the cortical dysfunction of Alzheimer's disease.     

Relationship between cognitive status and behavioral symptoms in Alzheimer's disease and mixed dementia

OBJECTIVE: To investigate the relationship between cognitive and behavioral impairments in Alzheimer's disease (AD) and to examine whether the addition of cerebrovascular disease modifies that relationship. DESIGN: Correlational analysis. SETTING: An outpatient dementia clinic. PATIENTS: An autopsy-confirmed series of 28 patients with AD and 16 patients with mixed Alzheimer and vascular dementia (MIX). MEASUREMENTS: Neuropsychological and behavioral tests during life: Mini-Mental State (MMS), Blessed Dementia Scale (BDS), Haycox Dementia Behavior Scale (HDBS), and two non-cognitive functional scales derived from the BDS and HDBS. RESULTS: In the AD group, MMS scores correlated significantly with scores on the BDS, HDBS, and two non-cognitive functional scales. In the MIX group, however, no significant relationship was observed between MMS scores and scores on any of the behavioral measures. CONCLUSIONS: These observations suggest that in AD, cognitive and behavioral impairments progress simultaneously. However, with the addition of a vascular component to the dementing process, cognitive and behavioral impairments may progress more independently.     

Dissociation between two forms of conceptual priming in Alzheimer's disease.

Patients with Alzheimer's disease (AD) and healthy control participants performed 2 conceptual repetition priming tasks, word-associate production and category -exemplar production. Both tasks had identical study-phases of reading target words aloud, had the most common responses as target items, and required production of a single response. Patients with AD showed normal priming on word-associate production but impaired priming on category-exemplar production. This dissociation in AD suggests that conceptual priming is not a unitary form of memory but rather is mediated by separable memory systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association of memory and cognition in Alzheimer's disease with volumetric estimates of temporal lobe structures.

The hypothesis that explicit memory impairment in Alzheimer's disease (AD) depends in part on hippocampal formation atrophy was tested in 47 persons with AD. Volumes of the hippocampal formation, parahippocampal gyrus, and temporal neocortex (excluding the hippocampal formation, amygdala, and parahippocampal gyrus) were estimated by reconstruction of magnetic resonance images. Tests of explicit memory, language, and constructional praxis were administered. Psychometric-volumetric associations were evaluated in regression analyses controlling for age, gender, education, and intracranial volume. Hippocampal formation volume was associated with a delayed-recall measure but not with immediate recall: temporal neocortical volume was correlated with performance on measures of language and constructional praxis. The results suggest that patterns of mnemonic and cognitive impairment in AD are due in part to differences in the distribution of pathology in the temporal lobe. (PsycINFO Database Record (c) 2010 APA, all rights reserved)