Naming errors in healthy aging and dementia of the Alzheimer type

Naming errors were analyzed for healthy younger and older adults and patients with a diagnosis of senile dementia of the Alzheimer type (SDAT). Three types of errors were identified, varying in relatedness to the target word: near synonyms; semantically related naming errors; and unrelated naming errors. Older adults made relatively more related errors than did younger adults. SDAT patients were distinguished by the number of unrelated responses given. In addition, SDAT patients who scored within the normal range were identified by the high number of response attempts relative to the number of initial errors. We suggest that error patterns on naming tasks may potentially serve as clinical markers to distinguish healthy older persons with mild naming disorders from patients with SDAT.     

Cerebrospinal fluid cholinesterases in aging and in dementia of the Alzheimer type

Protein concentration and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were assayed in the cerebrospinal fluid (CSF) of 26 healthy normal subjects (20-86 years old), 27 patients with dementia of the Alzheimer type (DAT), and 10 patients with dementia of the Alzheimer type with extrapyramidal signs (EDAT). In normal subjects, there was an age-related increase in CSF protein and AChE activity and a significant correlation (p less than 0.001) between CSF protein and BChE activity. In the DAT and EDAT groups, CSF AChE activities (mean +/- SD = 17.5 +/- 3.6 and 15.3 +/- 4.4 nmol/min/ml, respectively) were significantly lower (p less than 0.05) than in 13 age-matched control subjects (21.5 +/- 5.6 nmol/min/ml). In contrast, neither CSF protein concentration, BChE activity, nor the ratio of AChE/BChE differed significantly between groups. In patients with DAT, CSF AChE activity was significantly lower (p less than 0.05) in subjects with an early onset compared to those with a late onset (16.4 +/- 3.4 and 19.7 +/- 2.8 nmol/min/ml, respectively), and activity in the latter group did not differ significantly from control values. CSF AChE activity was not related to dementia severity and did not change significantly over an 18-month period. Although these results confirm a cholinergic deficit in patients with DAT, the considerable overlap of CSF AChE activity between groups and the nonsignificant correlation between AChE activity and dementia severity limit the usefulness of CSF AChE as a diagnostic marker of this disorder.     

Lymphocyte beta-adrenoceptor/effector complex in aging and dementia of the Alzheimer type

We examined density (Bmax), affinity (Kd), and norepinephrine (NE)-stimulated cyclic adenosine monophosphate (cAMP) generation of the beta-adrenergic receptor on lymphocytes in patients with dementia of the Alzheimer type (DAT, n = 13), in normal aged controls (AGED, n = 27), and in young controls (YOUNG, n = 21). Bmax (fmol/mg protein; mean +/- SD) was significantly lower in YOUNG (48.0 +/- 18.7) than in either AGED (64.8 +/- 22.3) or DAT (63.6 +/- 19.5, p less than 0.05). Receptor sensitivity, i.e., the fold increase of stimulated over basal cAMP generation (S/B), was higher in DAT (8.3 +/- 5.2) than in AGED (5.5 +/- 2.3) or YOUNG (5.4 +/- 2.6, p less than 0.07). This difference was due to a significant increase in S/B in female but not male DAT patients compared with AGED (p less than 0.05). There were no differences in levels of circulating NE between DAT and AGED, nor between sexes. Thus, the present data suggest that in this model of the postsynaptic beta-adrenergic receptor/effector complex, receptor sensitivity was increased in women with DAT.     

Neuropathological definition of Alzheimer disease: multivariate analyses in the morphometric distinction between Alzheimer dementia and normal aging

Although establishing that a patient is suffering from dementia of the Alzheimer type initially reflects a clinician's opinion, neuropathological study is for the present the most definitive examination to confirm the clinical diagnosis of Alzheimer disease. We review several comprehensive publications attempting on a quantitative basis to differentiate the changes occurring with normal aging of the human brain from those indicative of Alzheimer disease. New morphometric data on 5 histopathological lesions in the mesial temporal cortex of 42 subjects indicate that, when multivariate analyses are performed on such microscopic information, a diagnostic prediction about the brain of any unknown individual should indeed be possible with a statistically calculated degree of certainty.     

Memory, attention and evoked potentials during aging and in Alzheimer type senile dementia

A study of event-related brain potentials (ERPs) in Alzheimer type dementia has been performed on 6 elderly subjects (mean age: 67.5). Patients were included if they met DSM-III criteria for primary degenerative dementia. They presented important loss of memory function (in short-term memory-STM and long-term memory-LTM) and impairment of attention. They were compared to two groups: normal elderly subjects with no memory trouble and no attention dysfunction (12 subjects, mean age: 66) and elderly subjects with minor trouble in STM and little attention disturbance (6 subjects, mean age: 68.5). The chosen procedure is a dichotic listening and selective attention paradigm. Three series of tone bursts occurred in counterbalanced order (frequent tones: 1,000 Hz, 2,000 Hz; rare tones: 1,450 Hz). Rare/frequent ratio was 10/90. Subjects were asked to press a key to the rare tones. During the task, ERPs are recorded with 16 electrodes (cross montage), using 2 different reference electrodes sites: nasion and 7th vertebra. Results are displayed with the use of chronograms, spatio-temporal maps, reaction time histograms. In Alzheimer's group compared to the 2 others: N100, N200, P300 are significantly delayed in latency. P300 has a smaller amplitude. In Alzheimer's, P300 distribution on the scalp is more frequently founded of greater amplitude on the frontal region than on the centro-parietal region while the opposite is found in normal subjects. These results suggest that memory trouble or attention dysfunction are well correlated with the abnormalities of the ERPs.     

Periventricular white matter lucencies in senile dementia of the Alzheimer type and in normal aging

The significance of periventricular lucencies in the white matter on CT in demented patients is not understood. We studied the relationship of these changes to mental status of subjects with senile dementia of the Alzheimer type. A semiquantitative method showed more numerous and extensive lucencies in demented than in healthy elderly. Neuropathologic examination of five subjects with these changes and confirmed Alzheimer's disease revealed diffuse white matter pallor without infarction. There were no hypertensive vascular changes, although limited hyaline thickening was present.     

The GBS scale in multi-infarct dementia and senile dementia of Alzheimer type

The GBS profile was assessed for 39 patients with multi-infarct dementia (MID) and 34 patients with senile dementia of Alzheimer type (SDAT). The MID patients fulfilled the DSM-III criteria for multi-infarct dementia and had a score of 7 points or more on the Hachinski Ischemic Scale (HIS) and a score of 4 points or less on the Gustafson/Nilsson Alzheimer Scale (GNAS). The SDAT patients fulfilled DSM-III criteria for primary degenerative dementia and had a score of 5 points or more on the GNAS and a score of 6 points or less on the HIS. The total GBS score, the GBS subscale and relative subscale scores for intellectual functioning were significantly higher in patients with SDAT as compared with patients with MID. However, these subscale scores were considerably dispersed and nearly totally overlapping between patients with MID and SDAT, which implicates that the discriminative value is minimal. The validity between the GBS versus HIS and between the GBS versus GNAS was divergent, suggesting that the GBS scale has its own unique validity. In conclusion, the study does not support the hypothesis that the GBS profile may be of diagnostic value in clinical differentiation between multi-infarct dementia (MID) and senile dementia of Alzheimer type (SDAT).     

The Alzheimer myth and biomarker research in dementia

The focus of most of the research on Alzheimer's disease in the last decades has been on senile plaques and neurofibrillary tangles. The vast majority of patients with Alzheimer's disease are over 75 years of age, whereas most of the research focuses on younger subjects. To consider old-age dementia as a homogenous well-defined condition ignores the complexity of this condition and limits the development of new diagnostic methods, preventive strategies, or treatment strategies that could be widely applicable in daily practice in the majority of the older patients. The current research on biomarkers focuses on correlates of plaques and tangles, which are poor markers in older dementia subjects. Acknowledging that dementia in old age is an essentially different condition from dementia at relatively younger age is needed and should lead to new approaches in dementia research.     

Differential diagnosis of aging, dementia of the Alzheimer type and depression with EEG-segmentation

EEG segmentation can be used to measure altered brain function in aging and diseases of the brain. The parameter 'number of different segments' makes clear how many different potential fields are involved in brain activity during a given period of time. It should represent effects of aging and disease. To prove this assumption, 11 young and 10 aged controls, 12 patients with mild dementia of the Alzheimer type (DAT), 10 young and 12 aged patients with endogenous depression were included in the study. The number of different segments in the beta frequency band between 16 and 19.75 Hz was measured according to the theory of Lehmann et al. [Clinical Neurophysiology 1987;67:271-288], and the segments were classified by their location on the scalp. The Mann-Whitney U test was used for statistical comparison. Aged controls had more different segments than young controls (n = 21, U = 14, p < 0.0038). Patients with DAT had less different segments than healthy aged controls (n = 22, U = 18.5, p < 0.0061). Aged patients with endogenous depression had more different segments than patients with mild DAT (n = 24, U = 32, p < 0.021). The reduction of the number of different segments in DAT compared to controls and patients suffering from depression may be helpful for differential diagnosis. The higher number of different segments in aged versus young controls could be interpreted as a sign of increased complexity in the aged brain.     

The tropicamide test in patients with dementia of Alzheimer type and frontotemporal dementia

The tropicamide test was applied to 30 patients with probable Alzheimer's disease (pAD), 12 with frontotemporal dementia (FTD) and 46 healthy subjects. One drop of 0.01% tropicamide was instilled in one eye and one drop of saline solution in the other. The pupil diameter was measured with a Goldmann pupillometer in its basal condition and 10, 15, 20, 25, 30, 35, 45 and 55 minutes afterwards. The results do not show differences between pupil dilation observed in pAD and in FTD; in both groups, from the beginning of the test, the pupil dilated more than in healthy people. A high interindividual variability was observed. The best cutoff point is 38% of interpupillary difference at minute 25 (sensitivity = 63%, specificity = 80%). If we consider the prevalence of AD in a population over 40 years old to be 1.4%, the adjusted positive predictive value of the test would be 4.2%. According to these results, the test is not a true diagnostic marker of AD.     

Theory of mind and cognitive processes in aging and Alzheimer type dementia: a systematic review

Objectives: Theory of mind (ToM) performance in aging and dementia of the Alzheimer type (DAT) has been a growing interest of researchers and recently, theoretical trends in ToM development have led to a focus on determining the cognitive skills involved in ToM performance. The aim of the present review is to answer three main questions: How is ToM assessed in aging and DAT? How does ToM performance evolve in aging and DAT? Do cognitive processes influence ToM performance in aging and DAT?

Method: A systematic review was conducted to provide a targeted overview of recent studies relating ToM performance with cognitive processes in aging and DAT.

Results: Results suggest a decrease in ToM performance, more pronounced in complex ToM tasks. Moreover, the review points up the strong involvement of executive functions, especially inhibition, and reasoning skills in ToM task achievement.

Conclusion: Current data suggest that the structure of ToM tasks itself could lead to poor performance, especially in populations with reduced cognitive abilities.     

Cholinergic receptors in human brain: effects of aging and Alzheimer disease

A general review of cholinergic receptors in human brain is presented. The paper focuses upon changes in normal aging brain and in Alzheimer disease. Studies from five different approaches are reported: 1) molecular biology; 2) receptor binding studies; 3) studies with specific neurotoxins; 4) immunocytochemistry; and 5) PET scan. These studies document profound and characteristic differences between the normal aging and the pathological Alzheimer brain with regard to cholinergic receptor localization, distribution, and function.     

Depression in dementia of the Alzheimer type and in multi-infarct dementia

The authors used the Hamilton Rating Scale for Depression and a rating of depressed mood to investigate the prevalence of depression in 55 patients with Alzheimer's disease, 37 patients with multi-infarct dementia, and 30 nondemented comparison subjects. The prevalence of depressed mood depended on the severity of dementia as measured by the Mini-Mental State examination and was significantly lower among patients in more severe stages of Alzheimer's disease but not among patients with severe multi-infarct dementia.     

Cholinesterase activity in plasma, erythrocytes, and cerebrospinal fluid of patients with dementia of the Alzheimer type

Cholinesterases, including pseudocholinesterase (BChE) of human plasma and acetylcholinesterase (AChE) of erythrocytes and cerebrospinal fluid (CSF), have been considered as possible markers in dementia of the Alzheimer type (DAT). Reported data, however, are widely varied, and no significant pattern emerges when total enzyme activity is assayed. In the present studies, we have reexamined the relationship of ChE activities in DAT and control patients. ChE activity was measured in plasma, erythrocytes, and CSF from DAT patients and compared with normal controls as well as with samples from patients with a diagnosis other than DAT. Early age onset (presenile) and late age onset (senile) DAT were also compared. No significant differences in total enzyme activity were found in any of the comparisons. Calculations of AChE/BChE ratios in CSF also provided no significant indication of any changes in ChE activities in DAT. It is suggested that measurements of total AChE or BChE activity in these biological materials do not provide a useful index of alterations in central cholinergic function in patients with DAT.     

Cholinergic muscarinic binding by human lymphocytes: changes with aging, antagonist treatment, and senile dementia of the Alzheimer type

In peripheral blood lymphocytes (mixed lymphocytes isolated on a Ficoll-Hypaque density gradient) derived from normal human subjects, cholinergic muscarinic binding capacity was found to increase with age. In contrast, lymphocytes derived from patients with "probable" senile dementia of the Alzheimer type (SDAT) exhibited a marked reduction in binding capacity. Treatment of these patients with antimuscarinic drugs was associated with increased muscarinic binding by lymphocytes. These results indicate that cholinergic muscarinic binding by peripheral blood lymphocytes may be useful in the study of alterations associated with aging and SDAT, as well as in evaluating changes induced by certain cholinergic drug treatments.