D. Coakley

Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case–control study

Low n-3 polyunsaturated fatty acid (PUFA) status may be associated with neuro-degenerative disorders, in particular Alzheimers disease, which has been associated with poor dietary fish or n-3 PUFA intake, and low docosahexaenoic acid (DHA) status. The present case-control study used an established biomarker of n-3 PUFA intake (serum cholesteryl ester-fatty acid composition) to determine n-3 PUFA status in patients with Alzheimers disease, who were free-living in the community. All cases fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimers Disease and Related Disorders Association criteria for Alzheimers disease. Detailed neuropsychological testing and neuroimaging established the diagnosis in all cases. The subjects (119 females and twenty-nine males) aged 76.5 (SD 6.6) years had a clinical dementia rating (CDR) of 1 (SD 0.62) and a mini mental state examination (MMSE) score of 19.5 (SD 4.8). The control subjects (thirty-six females and nine males) aged 70 (SD 6.0) years were not cognitively impaired (defined as MMSE score <24): they had a mean MMSE score of 28.9 (SD 1.1). Serum cholesteryl ester-eicosapentaenoic acid and DHA levels were significantly lower (P<0.05 and P<0.001 respectively) in all MMSE score quartiles of patients with Alzheimers disease compared with control values. Serum cholesteryl ester-DHA levels were progressively reduced with severity of clinical dementia. DHA levels did not differ in patients with Alzheimers disease across age quartiles: all were consistently lower than in control subjects. Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR. It remains to be determined whether low DHA status in Alzheimers disease is a casual factor in the pathogenesis and progression of Alzheimers disease.

Measuring the Quality of Life of Dementia Patients Using the Schedule for the Evaluation of Individual Quality of Life

The importance of quality of life (QoL) assessment in research and clinical practice is gaining increasing recognition. The Schedule for the Evaluation of Individual Quality of Life (SEIQoL) is based on a phenomonological approach in which the individual’s views are central. As cognitive impairment may affect insight and the ability to make judgements this study explored the feasibility, validity and reliability of using the SEIQoL to measure the quality of life of elderly dementia patients. The SEIQoL was administered to 20 patients meeting DSM-IIIR criteria for mild dementia. Cognitive status was evaluated using the Mini-Mental State Examination (MMSE) and CAM COG (from the CAMDEX). All patients were able to complete some elements of the SEIQoL, but only 6 were willing or able to complete the full procedure. Mean CAM COG scores distinguished these 6 patients from the remaining 14 (p<.01). For these 6 dementia patients the mean internal variance (R2), an estimate of construct validity, was .70, and the i...

Dementia carer education and patient behaviour disturbance

To evaluate the impact of a dementia Carer Education Programme on carer quality of life (QoL), burden, and well‐being.

Clinical application of electrophysiological markers in the differential diagnosis of depression and very mild Alzheimer's disease.

BACKGROUND--Current evidence indicates that, on their own, neither flash visual evoked responses (FVEPs) nor event related potentials (ERPs) are sufficiently useful to the clinician in the very early stages of memory dysfunction. However, the possibilities for the combined use of these measures has not been fully explored. METHODS--This study examined the clinical utility of combined FVEP and ERP-P300 component latencies as predictive markers in 16 patients with Alzheimers disease, 15 patients with depression, and 21 control subjects. RESULTS--There were significant group differences in FVEP P2 latency (P = 0.004) between the controls and both the depressive patients and those with very mild Alzheimers disease. There were no statistically significant group differences for the ERP component (N2/P300) amplitudes or latencies. The P300 component latency was positively correlated with both the FVEP N2 and FVEP P2 component latencies in the patients with Alzheimers disease but not in the control subjects or the depressed patients. A discriminant function, using two ERP and two FVEP component measures, gave an overall correct classification rate for dementia of 78%. In this study of very mildly impaired patients the FVEP latencies provided a more sensitive marker for the presence of cognitive dysfunction than P300 latency delay. CONCLUSIONS--The findings support the use of multimodal evoked potentials in the differential diagnosis of very mild Alzheimers disease and normal aging.

Letter and Category Fluency in Alzheimer's Disease: A Prognostic Indicator of Progression?

This study investigated differential patterns of performance by 40 Alzheimers disease (AD) patients on standardised letter and category fluency tests. The performance of 24 age and education matched controls was used to classify patients as relatively more letter fluency impaired (L < C, n = 15) or more category fluency impaired (C < L, n = 25), and clinical features distinguishing these patient subgroups were investigated. Category performance was equally impaired in both patient subgroups, whereas the L < C subgroups were particularly impaired on letter fluency. The subgroups differed significantly in duration of illness (24 months for L < C group, 47 months for C < L group; t = 2.69, p = 0.01) but did not differ in global dementia severity, age, education, general language ability, or functional status. Data on annual rate of change (ARC) on the Mini-Mental State Examination were available for 26 patients. While not statistically significant, subgroup ARC differences were suggestive of more rapid decline in the L < C patients, consistent with the finding of shorter duration of illness in this group. Word fluency tests may have potential as early predictors of rate of progression in AD.

Primary auditory pathway and reticular activating system dysfunction in Alzheimer's disease

Patients with Alzheimers disease (AD) have pathologic involvement of several important components of the primary auditory pathway, including the inferior colliculus, medial geniculate body, primary auditory cortex, and secondary auditory cortex. The main components of the brainstem auditory evoked response (BAER) and middle latency response (MLR) reflect the function of portions of the primary auditory pathway, including those affected pathologically in AD. The amplitude of the P1 component of the MLR reflects the degree of neuronal activity of midbrain portions of the ascending reticular activating system (ARAS) with cortical cholinergic projections. To determine whether there is dysfunction of the primary auditory pathway and ARAS in AD, we compared simultaneous BAER and MLR component latency and amplitude measurements in patients with mild-moderate AD (n = 35) and age-matched healthy elderly controls (n = 34). There were significant latency delays in brainstem transmission time (BAER I-V interpeak latency; p < 0.05) and in primary auditory cortex evoked potential generation (MLR Pa latency; p < 0.05) in the AD group compared with controls. In addition, there was a significant reduction in the PI component amplitude of the MLR in the AD group (p < 0.01). These results indicate dysfunction of the primary auditory pathway and ARAS in patients with mild-moderate AD and support the hypothesis that impairment of auditory function and of arousal are intrinsic features of AD.

Classification of mild Alzheimer's disease by artificial neural network analysis of SPET data.

An evaluation of the performance of artificial neural networks (ANNs) for the classification of probable Alzheimers disease (pAD) patients was undertaken using data extracted from four regions of interest constructed on single photon emission tomographic (SPET) cerebral perfusion images. Two studies using feed-forward neural networks (FFNNs) were undertaken. The first was to determine if it would be possible to classify pAD patients and normal subjects in a mixed group, comprising 29 patients diagnosed as having pAD varying in severity from mild, established dementia to moderate dementia and 10 healthy control subjects. The second was to determine if the networks generated in the first study could prospectively classify 15 additional patients with very mild or mild cognitive impairment. The results were compared to those obtained using the same data and discriminant analysis. The relative performances of the two analysis techniques were assessed on the basis of the area under receiver operating characteristics (ROC) curves. The FFNN successfully classified all datasets in the first study, achieving an area under the ROC curve of 1.00, whereas discriminant analysis achieved 0.94. When tested on data from the second group, the areas under the ROC curves varied between 0.86 and 1.00 for the FFNN, whereas that for discriminant analysis was 0.99. We conclude that FFNNs can accurately classify pAD patients with mild to moderate dementia using data obtained from SPET cerebral perfusion images.

Are Hydrogen Breath Tests Valid in the Elderly

Hydrogen breath testing (HBT) is frequently used as an alternative to small bowel aspiration in the diagnosis of small intestinal bacterial overgrowth (SIBO). The role of the glucose HBT was assessed in 30 elderly patients. A positive HBT was recorded in 15 of 20 SIBO cases and 7 of 10 culture negatives (sensitivity 75% and specificity 30%). The correlation coefficients between hydrogen gas (H2) rise and total bacterial count (r = 0.21) and H2 rise and anaerobic count (r = 0) were not significant. Fasting H2 levels were raised in only 4 of the 20 SIBO cases. This study indicates that the HBT is not reliable in the diagnosis of SIBO in the elderly. There was no evidence from the data that different H2 levels or bacterial counts would significantly alter the reliability of the HBT. This work suggests that factors other than small bowel bacteria are involved in the production and expiration of H2 in the elderly, and that these factors need to be considered in the interpretation of this breath test.

Loneliness and vascular biomarkers: the Dublin Healthy Ageing Study

Loneliness has been associated with poor physical health and a link has been suggested between the presence of loneliness, cardiovascular health and inflammatory markers.

Distinguishing between Patients with Depression or Very Mild Alzheimer's Disease Using the Delayed-Word-Recall Test

The present study investigated the accuracy of an extended version of the Delayed Word Recall (DWR) test in distinguishing patients with very mild Alzheimers disease (AD) (Mini Mental State Examination score > or = 23) from community-dwelling depressed/dysthymic patients. The DWR test was administered to 26 non-depressed patients who, at the time of DWR administration or on follow-up, fulfilled NINCDS/ADRDA criteria for probable AD, and to 20 age-matched non-dementing patients with a diagnosis of major depression (n = 12) or dysthymia (n = 8) according to DSM-III-R criteria. Sensitivity and specificity were, respectively, 96 and 100% for DWR free recall, and 92 and 100% for DWR recognition. In this study both DWR free recall and recognition measures were highly sensitive and specific in distinguishing very-mild-AD patients from depressed/dysthymic patients. The investigation of more severely depressed patients is warranted.