Dementia and Geriatric Cognitive Disorders

Singleton, Andrew B.; Wharton, Anna; O’Brien, Kirsty K.; Walker, Matthew P.; McKeith, Ian G.; Ballard, Clive G.; O’Brien, John; Perry, Robert H.; Ince, Paul G.; Edwardson, James A.; Morris, Christopher M.

doi: 10.1159/000066022pmid: 12411758

Dementia with Lewy bodies (DLB) represents the second commonest cause of dementia in the elderly following Alzheimer’s disease (AD). Whilst the presence of Lewy bodies is essential, DLB shares with AD the presence of senile plaques (SP), but neurofibrillary tangles (NFT) are not a necessary feature. The apolipoprotein E (APO E) Ε4 allele is the most consistently associated genetic risk factor for AD and has also been shown to associate with DLB. We have therefore analysed the APO E Ε4 allele in a large series of DLB cases coming to autopsy to: (1) determine if the Ε4 allele describes a similar risk in DLB development as in AD and (2) determine how APO E Ε4 allele status correlates with clinical and neuropathological findings in DLB, and in AD, as an indication of the role of APO E in underlying disease biology. Both DLB and AD share an increased Ε4 allele frequency, though in DLB the Ε2 allele frequency is not reduced and there is a relative lack of Ε4 homozygotes. In contrast to previous studies, no association of the Ε4 allele with age at onset or duration of disease was found in either disorders. In DLB cases, overall a significantly shorter duration of illness was observed when compared with AD cases, though no significant effect of the Ε4 allele on disease onset or duration was seen. The survival rate was reduced by the presence of the Ε4 allele in DLB, as with AD. No effect on SP or NFT counts was seen with the Ε4 allele, though DLB cases showed a lower SP burden in addition to the expected lower NFT counts. This study demonstrates that DLB shares the APO Ε4 allele with AD as a common risk factor, but that there are differences in the way the Ε4 allele affects the phenotypic expression of disease.

Lin, Ker-Neng; Wang, Pei-Ning; Liu, Chia-Yih; Chen, Wei-Ta; Lee, Yi-Chung; Liu, Hsiu-Chih

doi: 10.1159/000066024pmid: 12411759

The purpose of this study of dementia screening was to obtain different cutoff scores of the Cognitive Abilities Screening Instrument, Chinese versions (CASI C-2.0) for subjects with different educational backgrounds. The diagnosis of dementia was based on the Diagnostic and Statistical Manual of Mental Disorders, ed 3 revised or ed 4 criteria. To diagnose Alzheimer’s disease, the guidelines of the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association was followed. The severity of dementia was determined on the Clinical Dementia Rating scale. Altogether 2,096 subjects, aged 65 years and more, were included. Of them, 1,178 were normal and 918 were demented. Their performance on CASI C-2.0 was influenced by their education and age. Gender difference on CASI C-2.0 scores was only significant in the illiterate, but not in the literate group. We recommend that the population be divided into three levels, namely those who (1) had no formal education (Edu = 0); (2) received 1–5 years of schooling (Edu = 1–5), and (3) received 6 or more years of education (Edu ≧6). The cutoff scores of CASI C-2.0 in the diagnosis of dementia in these three educational groups were as follows: Edu = 0: 49/50 (sensitivity = 0.83; specificity = 0.85); Edu = 1–5: 67/68 (sensitivity = 0.83; specificity = 0.91), and Edu ≧6: 79/80 (sensitivity = 0.89; specificity = 0.90).

Nägga, Katarina; Gottfries, Johan; Blennow, Kaj; Marcusson, Jan

doi: 10.1159/000066023pmid: 12411760

The two most frequently examined biomarkers in the diagnosis of dementia are cerebrospinal fluid (CSF) tau and β-amyloid_1–42 (Aβ_1–42). An assay for tau phosphorylated at threonine 181 (phospho-tau) has recently been developed. We studied these three markers in patients with possible Alzheimer’s disease (AD; n = 23), probable AD (n = 50), AD with relevant cerebrovascular disease (AD with CVD; n = 14), possible vascular dementia (VaD; n = 39), probable VaD (n = 36), cognitively impaired (n = 13) and 27 neurologically healthy controls. Compared with the controls, tau levels were significantly increased in possible AD, probable AD, AD with CVD and probable VaD. Aβ_1–42 was decreased in all dementia groups compared with the controls. In contrast, phospho-tau levels were increased only in probable AD compared with the controls. From the results of the present study, it is concluded that neither measurement of phospho-tau, tau nor Aβ_1–42 in CSF can discriminate entirely between dementia and cognitively non-disturbed controls or between dementia of different aetiologies in the clinical diagnostic procedure.

Sjögren, Magnus; Wikkelsö, Carsten; Östling, Svante; Wallin, Anders; Blennow, Kaj

doi: 10.1159/000066025pmid: 12411761

We considered it possible that the differences in clinical symptoms between two suggested subgroups of Alzheimer’s disease (AD), AD type I and AD type II, have biological correlates, for instance different metabolic profiles. Therefore, we performed regional cerebral blood flow (rCBF) measurements and investigated the cerebrospinal fluid (CSF) levels of the monoamine metabolites homovanillic acid (HVA), 5-HIAA, and HMPG in 15 patients with AD type I, in 36 patients with AD type II, in a control group and in a contrast group consisting of 16 patients with frontotemporal dementia. The results suggest that there are underlying biological correlates of the phenomenological discrepancies between AD type I and AD type II. For instance, a decreased CSF level of HVA (p < 0.001) was specific to AD type I and decreased rCBF (p < 0.05 to <0.001) in three particular regions was specific to AD type II.

Kantarci, Kejal; Xu, YueCheng; Shiung, Maria M.; O’Brien, Peter C.; Cha, Ruth H.; Smith, Glenn E.; Ivnik, Robert J.; Boeve, Bradley F.; Edland, Steven D.; Kokmen, Emre; Tangalos, Eric G.; Petersen, Ronald C.; Jack Jr., Clifford R.

Gabryelewicz, T.; Religa, D.; Styczynska, M.; Peplonska, B.; Pfeffer, A.; Wasiak, B.; Luczywek, E.; Golebiowski, M.; Androsiuk, W.; Czyzewski, K.; Przekop, I.; Barcikowska, M.

doi: 10.1159/000066020

doi: 10.1159/000067322pmid: N/A

doi: 10.1159/000067323pmid: N/A

doi: 10.1159/000067324pmid: N/A