Risk factors for transitions from normal to mild cognitive impairment and dementia.

OBJECTIVE: To identify risk factors associated with transitions from cognitively normal to various forms of mild cognitive impairment (MCI) and then from MCI into early dementia with death as a competing state. METHODS: Cognitive assessments from 554 subjects participating in a longitudinal study at the University of Kentucky AD Center were used to classify individuals into one of three transient states at any visit: cognitively normal, amnestic MCI, or mixed MCI. Between visits subjects could die or become demented. A series of polytomous logistic models were used to model transitions among these states over time and to determine how the log odds of these transitions vary with age, education, sex, family history of dementia, and APOE status. RESULTS: Age affects all transitions among transient states as well as those to dementia or death. Presence of at least one apolipoprotein 4 allele affects transitions from cognitively normal into amnestic MCI or into dementia. At most 12 years of education affects transitions into mixed MCI. Transitions do not vary with sex or family history. CONCLUSION: Aside from age, the usual risk factors associated with conversion from cognitively normal into dementia are likely risk factors for transitions into mild cognitive impairment.

Cognitive performance in Alzheimer's disease patients receiving rivastigmine for up to 5 years.

This analysis aimed to assess mini-mental state examination (MMSE) scores in patients with Alzheimer's disease who received rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, for up to 5 years. Rivastigmine data came from two pooled open-label extensions of four 6-month, randomised, placebo-controlled trials. Projections of decline, had the same patients not been treated, were made using a baseline-dependent mathematical model. MMSE data were available for 1998 rivastigmine-treated patients and 657, 298 and 83 were still on treatment at 3, 4 and 5 years, respectively. The mean (+/-SD) baseline MMSE score was 19.3 (+/-4.9). Projected mean scores in model-based untreated patients declined below 10 points on the MMSE at about 3 years, while the mean MMSE score of patients who remained on rivastigmine stayed above 10 points for 5 years.

Modelling mini mental state examination changes in Alzheimer's disease.

The Mini Mental State Examination (MMSE) is widely used to measure dementia severity in Alzheimer's disease patients. While changes over time in the MMSE due to dementia have been studied, the relationship between MMSE scores and the duration of disease course is less well understood. Using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) data, we modelled change in MMSE as a function of time for this population. For this purpose we used the interval between consecutive MMSE assessments as the time factor. We also investigated the impact of sex, education and age at testing on the resulting model. Analyses showed that Alzheimer's disease progression over time (ADP) can be modelled using a cubic or a logarithmic function of MMSE score. From these curves ADP can be obtained as a function of MMSE. These models demonstrate that there are different rates of change for various ranges of the MMSE. Additional analyses suggest that patient factors affect rates of ADP, younger patients and more educated patients progress more rapidly, while sex has little impact on ADP. Such estimations of disease course are useful when comparing different populations for both clinical and research purposes.

Single SPECT measures of cerebral cortical perfusion reflect time-index estimation of dementia severity in Alzheimer's disease.

UNLABELLED: To determine the relationship between cerebral cortical blood flow loss and the temporal development of the dementia in Alzheimer's disease (AD), SPECT was studied in a cross section of AD patients with a broad range of impairment. METHODS: Thirty patients with a diagnosis of probable AD had their mini-mental state examination scores transformed into time-index values to give an estimation of dementia severity relative to the developmental time course. SPECT images were obtained using 99mTc-ethyl cysteinate dimer and a 3-head camera. Cortical surface perfusion was analyzed, including modified Talairach standardization, to obtain cortical elements from the convexity (each representing about 0.25 cm2 at the surface, 6.6-mm cortical depth) referenced to the mean perfusion of the full greater cerebellar hemisphere. These element ratios were analyzed (individually and by averages of estimated Brodmann's areas and brain regions) using linear regression with the time-index value. RESULTS: For individual posterotemporal and inferoparietal Brodmann's areas (21, 22 and 39, 40, respectively) the correlation coefficients between cortical perfusion ratios and dementia severity ranged between -0.67 and -0.78 (P < 0.001). Perfusion ratios from these regions declined 2.5%-4.2% for each estimated year of progression. Prefrontal area perfusion showed less association with severity. Perfusion in primary cortical regions had no significant association with dementia severity. CONCLUSION: Cerebral cortical perfusion loss is temporally related to development of dementia. The spatial pattern of high, significant correlations between cortical perfusion and dementia severity shows a regional distribution that corresponds closely to the distribution of AD pathology described in autopsy studies.

A comparison of air-cavity inhomogeneity effects for cobalt-60, 6-, and 10-MV x-ray beams.

The inclusion of air-filled spaces in treatment fields creates a potential dosimetric problem due to the loss of charged particle equilibrium near the air-tissue interface. We have used a simulated larynx phantom and a small buildup/extrapolation chamber to compare the magnitude and spatial extent of underdosing and overdosing at the distal surface for two linear accelerators (10- and 6-MV x-rays) and a cobalt-60 machine. Surface doses were compared to doses measured in a similar but homogeneous phantom to give observed/expected ratios (O/E), which were greater than 1.0 for large field sizes and less than 1.0 for small field sizes on all machines. The minimum field sizes which produce no surface underdosing for a simulated 2-cm-diam larynx are roughly 7 X 7 cm for 10-MV x-rays, 6 X 6 cm for 6-MV x-rays, and 5 X 5 cm for cobalt-60. In addition, the depth over which underdosing occurs is seen to increase with increasing energy.