Dementia Of The Alzheimer Type Patients Research Articles

Platelet Monoamine Oxidase B Activity in Dementia

Platelet monoamine oxidase B (MAO-B) activity has been found to increase significantly in demented patients. For the first time, a 4-year follow-up of platelet MAO-B activity and Mini-Mental State (MMS) was performed in patients with probable dementia of the Alzheimer type (DAT) and age-matched controls. MAO-B activity of DAT patients increased significantly 2 years after the beginning of the study as compared with controls and remained significantly higher for the entire period of the examinations (p < 0.0001). The decrease of the MMS scores did not correlate with the time course of the increase of platelet MAO-B activity (Spearman rank correlation test). The decline of the MMS scores of DAT patients preceded the elevation of MAO-B activity. Since degenerative processes in brain areas which are responsible for cognitive function and are reflected by the MMS scores rather affect cerebral cholinergic than monoaminergic neurotransmitter systems, degeneration of the latter at late stages of DAT might be reflected by increased platelet MAO-B activity.

The value of REM sleep parameters in differentiating Alzheimer's disease from old-age depression and normal aging

Pseudodementia as a common trait in elderly depressives presents a major problem in gerontopsychiatry, especially for the differential diagnosis between Old-Age Depression (OAD) and Dementia of the Alzheimer Type (DAT). The present polysomnographic study examined parameters of sleep continuity, sleep architecture, and REM sleep to differentiate DAT from OAD. The investigation was based on the theoretical framework of the cholinergic-aminergic imbalance model of depression, the cholinergic deficit hypothesis of Alzheimer's disease and the reciprocal interaction model of Non-REM/REM sleep regulation, according to which REM sleep parameters should have high discriminative value to differentiate OAD and DAT. We investigated 35 DAT patients, 39 OAD patients and 42 healthy controls for two consecutive nights in the sleep laboratory. The DAT patients were in relatively early/mild stages of the disease, the severity of depression in the OAD group was moderate to severe. Depressed patients showed characteristic ‘depression-like’ EEG sleep alterations i.e. a lower sleep efficiency, a higher amount of nocturnal awakenings and decreased sleep stage 2. Sleep continuity and architecture in DAT was less disturbed. Nearly all REM sleep measures differentiated significantly between the diagnostic groups. OAD patients showed a shortened REM latency, increased REM density and a high rate of Sleep Onset REM periods (SOREM), whereas in DAT REM density was decreased in comparison to control subjects. REM latency in DAT was not prolonged as expected. To assess the discriminative power of REM sleep variables a series of discriminant analyses were conducted. Overall, 86% of patients were correctly classified, using REM density and REM latency measures. Our findings suggest that REM density as an indicator of phasic activity appears to be more sensitive as a biological marker for the differential diagnosis of OAD and DAT than REM latency. The results support the role of central cholinergic neurotransmission in REM sleep regulation and the pathogenesis of DAT and OAD.

A population-based analysis of qualitative features of the neuropsychological test performance of individuals with dementia of the Alzheimer type: Implications for individuals with questionable dementia.

Qualitative features of the neuropsychological test performance of individuals with dementia of the Alzheimer type (DAT) were examined in a population-based study. Qualitative error scores were derived from measures of verbal and figural memory, verbal fluency and confrontation naming for 38 patients with clinically diagnosed DAT, 236 normal elderly (NE) individuals, and 72 others who were questionably demented and at risk (AR) for DAT. Persons with DAT made a greater proportion of intrusion and perseverative errors, and more lexical and semantic naming errors, than the NE participants. These measures provided fair specificity but poor sensitivity for the diagnosis of DAT, and a logistic model based on these measures correctly classified 98% of the NE participants, but only 29% of the DAT participants. The AR participants demonstrated a pattern of errors that was highly similar to that of the DAT patients, and when their scores were subjected to the logistic model, 90% were classified as NE and 10% as DAT. These results indicate that specific error types that have been associated with DAT in self-referred or clinic-based samples also occur in the general population to a greater degree in individuals with DAT or questionable dementia than in NE individuals. Furthermore, these qualitative features may have some diagnostic usefulness in that their presence provides reasonable specificity for DAT or questionable dementia.

Delusions of theft in dementia of the Alzheimer type: a preliminary report.

Delusions of theft are commonly found in patients with dementia of the Alzheimer type (DAT). This report describes the frequency, onset, and characteristics of delusions of theft in DAT patients. The sample consisted of 54 geropsychiatric inpatients with DAT; delusions of theft were found in 30 (55.6%) patients. Two thirds of these patients had delusions of theft within 1 year after onset of illness. There were no significant differences in age, age of onset, duration of disease, years of education, or the Mini-Mental State Examination (MMSE) score between patients with and without delusions of theft. Delusions of theft frequently occur in the early stage of dementia, when the patients' cognitive impairments are relatively mild. The presence of this symptom may warrant a diagnosis of DAT.

Brain perfusion scintigraphy with99mTc-HMPAO or99mTc-ECD and123I-β-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease

Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2 beta-carboxymethoxy-3 beta-[4-iodophenyl]tropane (123I-beta-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of 99mTc-HMPAO or 99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was 2.5 +/- 0.4, with an increase to 5.5 +/- 1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was significantly reduced to 1.7 +/- 0.3, with a modest increase to 2.1 +/- 0.4 18 h after tracer injection (P < 0.05, Scheffe test, ANOVA). These results suggest that 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.

Computerized neuropsychological tests in the early detection of dementia: Prospective findings

This longitudinal study examines the sensitivity of 2 computerized neuropsychological tests, delayed matching to sample and paired associate learning, to early dementia of the Alzheimer type (DAT). Normal controls, patients in the early stages of DAT, and individuals with questionable dementia (QD) were studied. At 6 and 12 months after initial presentation, almost half of the QD group exhibited lower scores on the computerized subtests, maintaining their scores on standard testing. Over the same period NC subjects maintained their performance levels, while DAT patients continued to deteriorate. Linear discriminant function analyses of the computerized subtests at 6 and 12 months correctly classified 100% of the early DAT patients. Eighty-four and 79 percent of normal controls were correctly classified at 6 and 12 months respectively. Further development of these subtests for the detection of early dementia and the documentation of ongoing change in DAT is warranted. The findings are discussed in terms of the special sensitivity of these tests to the neuropathology of Alzheimer's Disease.

Response programming in dementia of the Alzheimer type: A kinematic analysis

Although planning is important for the functioning of patients with dementia of the Alzheimer Type (DAT), little is known about response programming in DAT. This study used a cueing paradigm coupled with quantitative kinematic analysis to document the preparation and execution of movements made by a group of 12 DAT patients and their age and sex matched controls. Participants connected a series of targets placed upon a WACOM SD420 graphics tablet, in response to the pattern of illumination of a set of light emitting diodes (LEDs). In one condition, participants could programme the upcoming movement, whilst in another they were forced to reprogramme this movement on-line (i.e. they were not provided with advance information about the location of the upcoming target). DAT patients were found to have programming deficits, taking longer to initiate movements, particularly in the absence of cues. While problems spontaneously programming a movement might cause a greater reliance upon on-line guidance, when both groups were required to guide the movement on-line, DAT patients continued to show slower and less efficient movements implying declining sensori-motor function; these differences were not simply due to strategy or medication status. Copyright©1996 Elsevier Science Ltd.

Category fluency is also predominantly affected in Swiss Alzheimer's disease patients.

To establish the comparative efficacy to differentiate between Swiss patients with dementia of the Alzheimer type (DAT) and elderly normal control subjects (NC) on two different verbal fluency tasks: category fluency and letter fluency. Fifty Swiss German DAT patients in the early stages of the disease and 50 matched normal control subjects were compared on letter and category fluency tasks. DAT patients exhibited an overproportional impairment on category fluency as compared with letter fluency. Receiver operating characteristic curves (ROC) showed that category fluency correctly classified a significantly higher number of DAT patients and NC subjects (84%) than letter fluency (70%). As similar findings have been described for English-speaking DAT patients, we conclude that deficiencies in category fluency are a general phenomenon, reflecting impaired structures of semantic knowledge occurring early in the course of Alzheimer's disease.

Longitudinal examination of American National Adult Reading Test (AMNART) performance in dementia of the Alzheimer type (DAT): validation and correction based on degree of cognitive decline.

The American National Adult Reading Test (AMNART) was constructed to provide a valid and stable estimate of premorbid verbal IQ (VIQ) in dementing individuals. However, recent studies have brought into question its validity in patients with dementia of the Alzheimer type (DAT). The present study was designed to longitudinally assess the validity of the AMNART in 40 DAT patients and 40 demographically matched normal control (NC) subjects. The results showed that VIQ estimates for patients with DAT were significantly lower than those of NC subjects and declined significantly over time with increasing dementia severity as measured by the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). An MMSE-based correction factor was derived for the DAT group which allows for the effective estimation of premorbid VIQ in these patients.

P366 Electroexpectogramme (EXG) at children with dehydratation caused by diarrhoea

Somatosensory ERPs and short latency somatosensory evoked potentials (SSEPs) were studied in patients with dementia of the Alzheimer type (DAT), those with vascular dementia, demented and non-demented patients with Parkinson's disease, and healthy control subjects. In control subjects, latencies of N140, P200, N240 and P300 components increased with age at a rate of 0.2, 0.2, 0.6 and 1.5 msec/year, respectively. Patients with DAT and demented patients with Parkinson's disease had normal SSEPs as well as normal P100, and N140 latencies, but patients with vascular dementia showed prolonged N140 and P200 latencies in addition to a prolonged central conduction time (CCT). Analysis of N140 and P200 components of somatosensory ERPs may be important for evaluation of patients with vascular dementia. In patients with DAT, those with vascular dementia and demented patients with Parkinson's disease, the P300 latency was significantly prolonged compared with that in age-matched control subjects. However, the P300 latency did not show any significant differences among the groups of demented patients.

Neuroleptic-Induced Parkinsonism in Elderly Patients Diagnosed With Psychotic Major Depression and Dementia of the Alzheimer Type

The authors prospectively examined elderly patients diagnosed with major depression with psychotic features (MD-P) and patients diagnosed with dementia of the Alzheimer Type (DAT) for neuroleptic-induced parkinsonism (NIP) during perphenazine treatment. Baseline parkinsonian symptoms did not differ between groups. With treatment, mean NIP score doubled in DAT patients but remained unchanged in the MD-P group. The difference between groups was highly significant and remained so after the effects of age, perphenazine dose, and duration of perphenazine treatment were controlled. Although the mechanisms underlying these differences in NIP development remain to be determined, clinical guidelines for neuroleptic dosages in elderly patients need to account for variability in neuroleptic tolerance between diagnostic groups.

A Neuropsychological Approach to the Rorschach in Patients with Dementia of the Alzheimer Type

This paper presents two neuropsychological approaches to using the Rorschach test with patients diagnosed with Dementia of the Alzheimer Type (DAT). The first approach examined Rorschach variables from the Comprehensive System (CS) within the context of the cardinal neuropsychological deficits. The second approach illustrated a "process approach" to scoring linguistic errors and perseverations on the Rorschach test via the introduction of a new scale. DAT patients were significantly different from normal comparison participants on selected CS variables but were not significantly different on CS measures of deviant verbalization and perseverations. Significant differences between the two groups were observed for linguistic errors and perseverations when the Rorschach protocols were rescored using the new scale. Furthermore, the types of linguistic and perseveration differences observed on the Rorschach test might be specific to the characteristic deficits of DAT. The findings are interpreted within a neuropsychological framework and are offered as support for the use of the Rorschach as a neuropsychological problem-solving test.

Naming and Knowing in Dementia of Alzheimer's Type

We studied the relationship between naming and the integrity of physical and associative knowledge in a group of patients with dementia of the Alzheimer type (DAT) and matched normal controls. All subjects named 48 line drawings and later generated verbal definitions in response to the names of a subset of the 48 items, which included a minimum of six definitions for correctly named objects and six definitions for items that the subject failed to name. A comprehensive scoring system was designed for the definitions, including physical and associative features of a general and a specific type, a superordinate label, the core concept, and various categories of errors. The definitions generated by the DAT patients, even those in the minimal group, contained significantly less correct information than those of normal subjects, and definitions corresponding to unnamed items were more impoverished than those for named items. Particularly striking was the loss of core concept for unnamed items. There was also a disproportionate reduction in physical information on unnamed compared to named items. We conclude that quantitative assessment of verbal definitions is a sensitive index of semantic memory breakdown. Our findings offer some support for the hypothesis that successful naming depends upon integrity of the subset of semantic knowledge comprising physical features.

1995 IPA/Bayer Research Awards in Psychogeriatrics. Bihemispheric language disorders in early-stage dementia of the Alzheimer type: evidence from a novel metalinguistic task.

Because dementia of the Alzheimer type (DAT) is commonly characterized by bilateral cerebral atrophy, we examined the issue of higher linguistic abilities lateralized to the right cerebral hemisphere (RH) in earlystage DAT. A modified version of an insertion task was administered to 14 patients with probable DAT, 8 right-hemisphere brain-damaged (RHD) patients, 8 left-hemisphere brain-damaged (LHD) patients, and 28 normal elderly (control, CTR) right-handed subjects. The task consisted of presenting the subjects with 53 well-formed sentences; in each a word or syntagm had to be inserted grammatically. Twenty-eight word/syntagm insertions required grammatical role reassignment of a lexical item in the stimulus sentence (shift, sensitive to RHD); 25 insertions implied only semantic reinterpretation of the target sentence (nonshift, sensitive to LHD). The three pathological groups were relatively and similarly impaired on standard aphasia assessment. The performances of the DAT patients, controlled for global cognitive verbal proficiency, verbal cognitive skills, and mood, were found to be significantly worse than the performances of the CTR group on both insertion subtests, whereas there were no significant differences between the DAT and RHD subjects on the shift items or between the DAT and LHD subjects on the nonshift items. Similarly, no differences were noted between the RHD and CTR nonshift scores, or between the LHD and CTR shift scores. On the other hand, the LHD group outscored the RHD group on the shift insertions. A comparison between the two insertion subtests revealed that only the RHD and DAT groups performed significantly worse on the shift than on the nonshift items. Results are consistent with other anecdotally reported RH-specific language-related disorders in early DAT and replicate previous findings of bihemispheric extralinguistic disturbances in these patients.

Personality change in dementia of the Alzheimer type

Although cognitive impairment is the predominant feature of dementia, personality changes are also frequently reported. This study aimed to describe the nature of personality change in dementia of the Alzheimer type (DAT) and the relationship of this change to cognitive decline. An informant-based instrument was developed based on a personality inventory designed by Lewis Goldberg for measuring personality in the normal population. Twenty-eight clinicians used this inventory to rate the difference between people suffering from DAT and normal elderly people. Differences were found in all five factors of personality, with Conscientiousness and Intellect showing the most difference and Agreeableness showing the least difference. Based on the findings of this first study, a smaller questionnaire of 46 traits was developed. This was completed by 50 relatives of DAT patients, 50 relatives of controls and 167 carers of dementia sufferers recruited from Alzheimer’s Association support groups. Principal components analysis revealed a large factor which accounted for 33% of the variance suggesting a global change in personality. Rotation revealed three meaningful factors. Two of these factors were highly correlated to cognitive decline while the third showed only a moderate correlation. The significance of these results is discussed.

Random number generation in dementia of the Alzheimer type: A test of frontal executive functions

The quality of attempts at generating a random sequence of the numbers 1–6 was studied in 30 patients with dementia of the Alzheimer type (DAT) and 30 elderly normal control (NC) subjects. Three main findings emerged: (1) DAT patients' subjective random sequences were more stereotyped (contained fewer digit combinations) than those of NC subjects. (2) This difference in response stereotypy was due to patients' enhanced tendency to arrange consecutive numbers in an ascending series (‘counting bias’). (3) In the patient group, degree of sequential nonrandomness was positively correlated with overall severity of dementia and with the extent to which performance on neuropsychological tests specifically assessing executive functions (fluency, naming, error monitoring) was impaired. These results illustrate a loss of behavioral complexity in the course of dementia and are interpreted as reflecting a frontal dysexecutive syndrome in DAT.

1H-MRS, MRI-based hippocampal volumetry, and 99mTc-HMPAO-SPECT in normal aging, age-associated memory impairment, and probable Alzheimer's disease.

To better understand how to differentiate the "in vivo" normal aging brain from pathological conditions, namely dementia of the Alzheimer type (DAT), by means of magnetic resonance imaging (MRI), single photon emission computerized tomography (SPECT), and proton magnetic resonance spectroscopy (1H-MRS), to show neuroanatomical, perfusional and neurochemical details, respectively. 1H-MRS, MRI-based hippocampal volumetry and 99mTc-HMPAO SPECT were performed in healthy older subjects as well as patients suffering from age-associated memory impairment (AAMI) and dementia of Alzheimer type (DAT). Eighteen subjects were selected from those referred to an outpatient clinic for diagnostic evaluation of cognitive impairment entered the study. Six patients fulfilled NINCDS-ADRDA diagnostic criteria for DAT, six subjects were affected by AAMI, and six cognitively healthy subjects, selected from among relatives of the patients, were defined as controls. The 1H-MRS and MRI studies were performed on a 1.5 Tesla NMR-imaging system equipped with a spectroscopy research package. SPECT scans were performed on a Gamma 11 computer system. 1H-MRS showed significantly lower N-acetylasparatate concentration in DAT and AAMI compared with controls. Conversely, mean inositol concentration was significantly higher in DAT than in controls, whereas AAMI subjects registered intermediate values. MRI measurements showed significantly reduced volumes of hippocampal formations in DAT and AAMI groups compared with controls. Finally, 99mTc-HMPAO SPECT showed a significant frontal, temporo-parietal, and occipital hypoperfusion in DAT patients only. These findings support the hypothesis of a continuum among the three conditions studied, or at least between AAMI and DAT, where AAMI seems to be an early, monosymptomatic stage of Alzheimer disease. Accepting this view, it would be questionable to maintain the term "age-associated memory impairment" as a discrete entity.

Neuroleptic-Induced Parkinsonism in Elderly Patients Diagnosed With Psychotic Major Depression and Dementia of the Alzheimer Type

The authors prospectively examined elderly patients diagnosed with major depression with psychotic features (MD-P) and patients diagnosed with dementia of the Alzheimer Type (DAT) for neuroleptic-induced parkinsonism (NIP) during perphenazine treatment. Baseline parkinsonian symptoms did not differ between groups. With treatment, mean NIP score doubled in DAT patients but remained unchanged in the MD-P group. The difference between groups was highly significant and remained so after the effects of age, perphenazine dose, and duration of perphenazine treatment were controlled. Although the mechanisms underlying these differences in NIP development remain to be determined, clinical guidelines for neuroleptic dosages in elderly patients need to account for variability in neuroleptic tolerance between diagnostic groups. The authors prospectively examined elderly patients diagnosed with major depression with psychotic features (MD-P) and patients diagnosed with dementia of the Alzheimer Type (DAT) for neuroleptic-induced parkinsonism (NIP) during perphenazine treatment. Baseline parkinsonian symptoms did not differ between groups. With treatment, mean NIP score doubled in DAT patients but remained unchanged in the MD-P group. The difference between groups was highly significant and remained so after the effects of age, perphenazine dose, and duration of perphenazine treatment were controlled. Although the mechanisms underlying these differences in NIP development remain to be determined, clinical guidelines for neuroleptic dosages in elderly patients need to account for variability in neuroleptic tolerance between diagnostic groups.

Peripheral antioxidant enzyme activities and selenium in elderly subjects and in dementia of Alzheimer's type—Place of the extracellular glutathione peroxidase

Defenses against free radical damage were determined in red blood cells and plasma from 40 patients with dementia of the Alzheimer-type (DAT) and 34 aged control subjects with normal cognitive function. No crude significant difference in erythrocyte copper-zinc superoxide dismutase (E-CuZnSOD), seleno-dependent glutathione peroxidase (E-GSH-Px), glutathione reductase (E-GSSG-RD) activities, and selenium (Se) concentration was found between DAT cases and control subjects. The peroxidation products evaluated in plasma by the thiobarbituric-reactive material (TBARS) were at the same level in the DAT group as compared to controls. In the DAT group, plasma GSH-Px (P-GSH-Px) activity and plasma Se (P-Se) were negatively correlated with age ( r = -0.58; p < 0.001 and r = -0.63; p < 0.001 respectively). Moreover, erythrocyte GSH-Px activity and Se were also negatively correlated with age ( r = -0.40; p < 0.01 and r = -0.46; p < 0.01, respectively). No significant correlation with age was observed in the controls. When controlling for age, a significant increase for P-GSH-Px activity and P-Se was observed in DAT patients as compared to controls. These significant differences mostly appeared in DAT subjects under 80 years. Some correlations were only observed in the DAT group such as P-GSH-Px and E-GSH-Px ( r = +0.68; p < 0.001); P-GSH-Px and E-Se ( r = +0.79; p < 0.001). Correlations between P-GSH-Px and P-Se, E-GSH-Px and P-Se, and P-Se with E-Se are greater in the DAT group ( r = +0.84; p < 0.001; r = +0.76; p < 0.001 and r = 0.75; p < 0.001) than in the control group ( r = 0.54, pI < 0.01; r = 0.43, p < 0.01 and r = +0.34, p < 0.05 respectively). The fact that first—a significant increase in P-GSHPx and P-Se, second-some modifications in the relationships between antioxidant parameters, and third-age-dependent decreases of glutathione-peroxidase activities and their cofactor, appeared only in the DAT group suggest that DAT is associated with an oxidative stress due to an imbalance between reactive oxygen species and the peripheral antioxidant opposing forces

Neuropsychological investigation of anterior and posterior cortical function in early-stage probable Alzheimer's disease.

In vivo neuroimaging studies have generally indicated a greater involvement of posterior cortical areas in early-stage dementia of the Alzheimer type (DAT) relative to frontal involvement. By contrast, some recent neuropsychological studies have shown that DAT patients perform poorly in frontal lobe tasks even in the early stages of the disease, although there is disagreement as to whether this necessarily implicates frontal pathology. The main aim of this study was to examine the hypothesis prompted by both neuroimaging studies and the traditional clinical conception of the disease, that, compared with the functioning of posterior association cortex, executive functions (thought to depend on frontal lobe integrity) are relatively spared in the early stages of DAT. A group of patients with a diagnosis of early-stage, probable DAT (n = 17) was compared with age- and IQ-matched controls (n = 17) across a range of neuropsychological tasks presumed to exercise frontal or temporoparietal functions. A profile of strengths and weaknesses was observed across 'anterior' and 'posterior' cognitive tests, including dissociations among some tests of temporoparietal function, in particular visual object perception (impaired) and spatial analysis skills (intact). Thus there was little support for the notion that the disease progresses cortically in a posterior-to-anterior direction. Possible reasons for the discrepancy between neurophysiological and neuropsychological observations are discussed, including the possibility that neuropsychological tests do not provide a valid indication of regional brain function when used in the context of DAT. Caution is urged in the clinical application of 'frontal lobe tests' for the differential diagnosis of DAT.