Reduced alpha4beta2*-nicotinic acetylcholine receptor binding and its relationship to mild cognitive and depressive symptoms in Parkinson disease.

CONTEXT: Cognitive or depressive disorders are frequently noted in patients with Parkinson disease (PD) and may be related to altered signaling through alpha4beta2*-nicotinic acetylcholine receptors (alpha4beta2*-nAChRs). OBJECTIVE: To assess the availability of alpha4beta2*-nAChRs and their relationship to mild cognitive and mild depressive symptoms in vivo in patients with PD. DESIGN: Crossover comparison between patients with PD and healthy volunteers (control group) using the alpha4beta2*-nAChR-specific radioligand 2-[(18)F]fluoro-3-(2[S]-2-azetidinylmethoxy)-pyridine (2-[(18)F]FA-85380) and positron emission tomography. SETTING: Departments of Neurology and Nuclear Medicine, University of Leipzig, Leipzig, Germany. PARTICIPANTS: Twenty-two nonsmoking patients with PD and 9 nonsmoking healthy volunteers. MAIN OUTCOME MEASURES: Level of 2-[(18)F]FA-85380 binding potential (2-FA BP), a measure of alpha4beta2*-nAChR availability. The relationship between severity of cognitive symptoms as rated using the Mini-Mental State Examination and DemTect scale and the level of depressive symptoms as indicated using the Beck Depression Inventory, and 2-FA BP were assessed. RESULTS: In patients with PD compared with healthy volunteers, there was widespread reduced 2-FA BP, especially in the midbrain, pons, anterior cingulate cortex, frontoparietal cortex, and cerebellum. In subgroups of patients with PD with possible depression, reduced 2-FA BP was most pronounced in the cingulate cortex and frontoparieto-occipital cortex, whereas in patients with PD with mild cognitive impairment, 2-FA BP was reduced in the midbrain, pons, and cerebellum. In patients with PD, the strongest associations between depressive symptoms and reduced 2-FA BP were noted in the anterior cingulate cortex, putamen, midbrain, and occipital cortex. In contrast, cognitive symptoms correlated only weakly with reduced 2-FA BP in the thalamus, midbrain, temporal cortex, hippocampus, and cerebellum. CONCLUSIONS: There is a broad reduction of alpha4beta2*-nAChR availability in patients with PD without clinically manifest dementia or depression compared with healthy volunteers. Reduced alpha4beta2*-nAChR binding in patients with PD within the subcortical and cortical regions is associated with the severity of mild cognitive or depressive symptoms. These results provide novel in vivo evidence for a role of the cholinergic neurotransmission in psychiatric comorbidity of PD.

Does a reliable decline in Mini Mental State Examination total score predict dementia? Diagnostic accuracy of two reliable change indices.

BACKGROUND/AIM: Norms for change in Mini Mental State Examination (MMSE) total score suggest that only a decline of at least 2-4 points indicates a reliable change. However, it is unknown whether change norms (Reliable Change Indices, RCIs) of the MMSE total score are suitable to predict future dementia. METHODS: 554 elderly individuals aged 75 and over without dementia at the first 2 visits were tested with the MMSE at a maximum of 6 visits with 1.5-year intervals. Two different RCIs for change in MMSE score (first to second visit) were computed - one RCI which corrects for practice and one RCI which corrects for regression to the mean. The main outcome measure was the diagnosis of dementia. RESULTS: During the study, 88 persons developed dementia. RCIs were significantly associated with future dementia diagnosis. The best cutoff for raw change in MMSE total score to predict dementia was -1 point (sensitivity = 48%, specificity = 67%, relative risk = 1.6). With the RCI + regression to the mean, the diagnostic accuracy was moderate (sensitivity = 61%, specificity = 72%, relative risk = 3.2). CONCLUSION: A change in MMSE total score is significantly associated with future dementia, but the diagnostic accuracy for dementia prediction is rather low.

[Mild cognitive impairment and development of dementia]. / Leichte kognitive Beeinträchtigungen und Demenzentwicklung.

OBJECTIVE: In order to identify mildly cognitively impaired subjects, MILD COGNITIVE IMPAIRMENT: (MCI) represents a current and well-discussed concept. Prevalence and conversion rates, relative risks and data on the sensitivity and specifity of MCI for the development of dementia will be calculated. METHODS: 980 subjects aged 75 years and over who participated in the Leipzig Longitudinal Study of the Aged (LEILA 75+) were clinically interviewed and cognitively tested at regularly intervals over a mean period of six years. RESULTS: At baseline, the prevalence of MCI was 19.3 %, including (original) and 41.5 % excluding (modified) the criterion of subjective cognitive complaints. Diagnoses of original and modified amnestic MCI-subtypes were associated with relative risks of more than three for the development of dementia. CONCLUSIONS: MCI represents a risk factor for dementia, mainly if the cognitive impairments are related to the area of memory. However, in order to predict dementia reliably, further findings (e. g. biomarkers) are required.

Direct costs associated with mild cognitive impairment in primary care.

BACKGROUND/AIMS: Little is known about the direct costs of individuals with Mild Cognitive Impairment (MCI). This study investigates the direct costs associated with MCI according to recent diagnostic criteria from a societal perspective. METHODS: Four hundred and fifty-two primary care patients aged 75+ from Leipzig, Germany, were investigated in face-to-face interviews regarding MCI according to the current diagnostic criteria of the International Working Group on MCI, resource utilisation and costs (questionnaire of service utilisation and costs), as well as chronic medical illness (Chronic Disease Score). Resource utilisation was monetarily valued using 2004/2005 prices. RESULTS: Mean annual direct costs were 4,443 euro for patients with MCI (n=39) and 3,814 euro for patients without MCI (n=413) (p=0.34). Looking at the cost components, patients with and without MCI only significantly differed regarding pharmaceutical costs (1,210 euro vs 1,062 euro; p<0.05) not caused by antidementive drugs. CONCLUSION: Direct costs of individuals having MCI are not significantly increased in comparison to direct costs of individuals without cognitive deficits.

[Measuring cognitive change in patients with suspected dementia--change norms are lacking for psychometric instruments]. / Messung kognitiver veränderung bei verdacht auf demenz--zur fehlenden normierung psychometrischer verfahren fü die verlaufsbeurteilung.

A diagnosis of dementia as well as of mild cognitive impairment requires evidence of cognitive decline over time. Often, cognitive tests are administered to objectively measure cognitive change. However, changes in psychometric test scores do not necessarily result from true cognitive change. They might also be due to chance and to normal variability. This paper discusses why change norms are required for a reasonable interpretation of individual changes in test scores. Norms for change are lacking for most psychometric instruments used for dementia diagnosis in the German-speaking area.

Measuring cognitive change in older adults: reliable change indices for the SIDAM.

BACKGROUND: In clinical settings, neuropsychological tests and screening instruments are often used to measure cognitive change over time. However, the interpretation of changes in test scores is often difficult. For most instruments there is no information how much change occurs normally in cognitively healthy individuals. AIM: To examine what is a reliable change for a widely used screening instrument for cognitive impairment and dementia. METHODS: A Sample of 119 cognitively normal elderly individuals aged 75 and over participated in the Leipzig Longitudinal Study of the Aged (LEILA 75+). All participants have been tested six times at 1.5 year intervals with the test part of the SIDAM over a mean period of 7.1 years. Reliable change indices (RCI) were computed for a common confidence interval (90%). It is demonstrated how to compute RCI for individual patients. RESULTS: In repeated assessments with 1.5 year intervals, a change in SIDAM score of at least 4 to 7 points (dependent on which of the six assessments were compared) indicates a reliable change at the 90% confidence level. Smaller changes can be interpreted only with high uncertainty. CONCLUSION: The interpretation of changes in test scores in older adults should account for potential practice effect, normal decline and regression to the mean.

Does the hippocampal atrophy correlate with the cortical theta power in elderly subjects with a range of cognitive impairment?

A previous study with a small sample (N = 39) showed a significant correlation between the cortical theta activity and the hippocampal volume in different stages of cognitive impairment in aged subjects. The recent study was aimed to replicate these results in a much bigger sample. The authors examined a sample of 121 right-handed subjects. The sample consisted of 37 healthy controls, 40 patients with questionable dementia, and 44 patients with mild dementia assessed by Clinical Dementia Rating. All subjects underwent EEG and brain MRI. Mean spectral power was calculated, and volume of hippocampal segments was measured. EEG theta power of the left and right hemisphere correlated significantly with the hippocampal volume on the left and right side in different stages of cognitive impairment. An increase of theta power was associated with decreased hippocampal volume. No other significant correlations were found for alpha or beta band power. No correlation was found between cortical theta and global brain volume. There seems to be a direct relationship between neuronal loss of the hippocampus and changed cortical theta activity for different stages of cognitive impairment in aged subjects.

Morphometry of the amygdala in patients with questionable dementia and mild dementia.

The volume of the amygdala is reduced in advanced Alzheimer's disease (AD). However, there is controversy whether amygdala atrophy is present in mild AD and in the transitional phase between health and the onset of dementia. The aim of this prospective longitudinal study was to investigate whether amygdala atrophy is present in subjects with questionable dementia and mild dementia and whether amygdala volume is associated with the future rate of cognitive change, that is the annual change in the Mini Mental State Examination (MMSE). At baseline, volumes of the amygdala were measured in 97 participants aged 70-87 years (40 controls, 33 patients with questionable dementia, 24 patients with mild AD) using magnetic resonance imaging. Eighty-six participants were clinically re-examined after 2.3 years on average. At baseline, significant differences in mean amygdala volume were found between controls and participants with mild AD. There was no significant correlation between the longitudinal annual change in MMSE and the baseline amygdala volume in any of the three groups.

Serum lipids and hippocampal volume: the link to Alzheimer's disease?

The association between hippocampal volume (as a presumed index of Alzheimer's disease pathology) with serum total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was studied in 86 elderly subjects with a range of cognitive functions. High-density lipoprotein cholesterol, but not low-density lipoprotein cholesterol or total cholesterol, was associated with hippocampal volume and dementia. This is compatible with protective effects of high-density lipoprotein cholesterol on hippocampal atrophy and Alzheimer's disease.

Structural correlates of mild cognitive impairment.

The structural correlates of mild cognitive impairment (MCI) were examined in 105 elderly subjects whose cognitive function ranged from intact to demented, including 38 subjects with MCI. Hippocampal volumes (left and right HcV), brain volume (BV), and grey matter volume (GMV) and white matter volume (WMV) were segmented from high resolution magnetic resonance data sets and normalised to intracranial volume (ICV). Hippocampal volume reductions, but not global brain, white or grey matter atrophy, were associated with MCI. White matter lesion severity did not differ over cognitive states. In multiple logistic regression models, normalised HcV and ICV (indicating premorbid brain volume) were significant predictors of MCI versus normality. Normalised BV and ICV significantly predicted dementia versus MCI. Absolute volumetric measures of HcV and BV yielded comparable classification accuracies. Hippocampal atrophy may be the crucial step for the transition from normality to MCI. Widespread brain atrophy may be the step to determine the transition from MCI to dementia. Brain volume reserve effects appear to be involved in both of these steps.

The relationship between head size and intracranial volume in elderly subjects.

OBJECTIVE: To study the relationship between parenchymal head volume (PHV) and intracranial volume (ICV), and to compare the ability of these two measurements to reflect the association between maximum mature brain volume and late-life cognition. METHODS: An elderly sample of humans with a range of cognitive functions from normality, via mild cognitive impairment (MCI) to dementia (mean age 78.6, S.D. 2.8; mean MMSE 25.4, S.D. 4.2) was examined. Head-to-head measurements of ICV and parenchymal head volume (PHV) were obtained from three-dimensional T1 weighted magnetic resonance images using automated procedures. Analyses of cognitive functions were based on continuous and categorial variables. RESULTS: PHV explained 55% of the variance in ICV. The ratio between PHV and ICV remained constant with increasing age and cognitive impairment. Measurements of PHV and ICV yielded comparable correlations with global cognitive performance. Group differences over gender and cognitive states were equally present in ICV and PHV. The relative risks of cognitive impairment that were associated with either small ICV or PHV were comparable. CONCLUSIONS: Measures of PHV can be considered as useful estimates of ICV and cerebral volume reserve.

Theta-power differences in patients with mild cognitive impairment under rest condition and during haptic tasks.

The aim of this study was to investigate spectral EEG theta-power during perceptive-cognitive demands in age-homogeneous groups of subjects with mild cognitive impairment (MCI), mild dementia (MDE), and a healthy control (CO) group. The present study includes 51 subjects (23 males, 28 females). We used the scales of the CDR (clinical dementia rating) to assign the subjects to the different groups. EEG data were collected during 10 minutes rest condition with eyes closed and during haptic perception test. The quality of the haptic reproductions differed significantly between CO and MCI, as well as between CO and MDE. The statistical comparison between EEG theta-power under rest condition and theta-power during haptic tasks revealed a significant decrease in theta-power during haptic tasks in all three groups over parieto-occipital regions. During haptic tasks, the theta-power was significantly different between CO and MDE over occipital regions and over parieto-temporal regions. A significant difference between CO and MCI was only revealed over right occipital regions (O2). Spectral theta-power during haptic tasks is a suitable measure to distinguish healthy subjects (CO) from patients with MCI respectively MDE. The results show that haptic tasks are sensitive to early perceptive-cognitive and functional deficits in patients with MCI.