Differentiation between Alzheimer's disease and multi-infarct dementia: Spect vs MR imaging

Single photon emission computed tomography (SPECT) and magnetic resonance (MR) imaging data were obtained in 11 patients with dementia of the Alzheimer type (DAT), 11 with multi-infarct dementia (MID) and nine elderly, healthy controls. All patients with dementia tolerated a 15-minute SPECT scan while six patients (27%) did not tolerate the MR examination due to the long acquisition times and/or claustrophobia. Blind qualitative rating of SPECT scans differentiated correctly between dementia and controls in 90% of cases (p < 0.0001; positive predicted value of 91%) and between clinically defined DAT and MID in 77% of cases (p < 0.01; positive predicted value of 80%). It correctly identified clinical group membership (control, DAT or MID) in 71% of cases (p <0.001; predicted positive value of 94%) but failed to differentiate between DAT and MID (positive predicted value of 50%). Overall, MR imaging correctly identified clinical group membership in 61% of cases (p < 0.01). Semiquantitative SPECT data demonstrated reduced regional cerebral blood flow (rCBF) in all regions of interest (ROI) except right frontal and right anterior parietal in both DAT and MID compared with controls (p < 0.05). There was no statistically significant difference between DAT and MID subjects in rCBF in any ROI. Several correlations between rCBF and cognitive variables were found in the MID but not the DAT group. Though the sample in this study is small, our findings suggest that Tc-99m HMPAO SPECT is a useful and practical tool in the assessment of patients with dementia. It enables the differential diagnosis of dementia and by using semiquantitative data it helps to establish the severity of disease.     

Prolactin responses to thyrotropin-releasing hormone in multi-infarct dementia and senile dementia of the Alzheimer type

The serum prolactin (PRL) responses to stimulation with thyrotropin-releasing hormone (TRH) (500 micrograms Protirelin) were compared in 14 patients with multi-infarct dementia (MID) and 10 patients with senile dementia of the Alzheimer type (SDAT). Between the MID and the SDAT patients, there were no statistically significant differences in the median serum PRL concentrations, median changes in serum PRL concentrations or median proportional changes in serum PRL concentrations. Further, the serum PRL responses did not correlate with the GBS scale scores (degrees of dementia) or the GBS subscale scores (clinical profiles, including motor functioning, emotional functioning and intellectual functioning). In conclusion, the study does not support the hypothesis that serum PRL responses to TRH stimulation are of diagnostic value in differentiating between MID and SDAT.     

Patterns of neuropsychological impairment in mild dementia: a comparison between Alzheimer's disease and multi-infarct dementia

The objective was to investigate the clinical and psychometric differences between patients with dementia of Alzheimer type (DAT) and patients with multi-infarct dementia (MID), matched for age, sex, education, and severity. Sixteen patients with DAT, 16 patients with MID, and 30 healthy individuals, were drawn from a longitudinal study on aging and dementia. Subjects with medical or previous mental disorders were excluded. DAT and controls with focal brain abnormalities on magnetic resonance imaging (MRI) were excluded. Diagnosis of dementia was carried out according to DSM-III-R criteria. Dementia severity was staged using the Clinical Dementia Rating (CDR) scale, and only patients with a score of 0.5-1 on CDR were studied. The main outcome measures were quantitative clinical scales of the assessment of global mental status, depression and anxiety, as well as a wide battery of neuropsychological tests for the evaluation of executive/conceptual functions and memory, as well as attention verbal ability, and visuospatial skill functions. The performance of demented patients compared to normal controls was affected on all measurements except for depression and anxiety. DAT patients showed compared to MID patients a greater extent of impairment on tasks assessing verbal comprehension and memory while MID patients were more significantly impaired on measures of frontal lobe functioning. Clinically matched DAT and MID patients show a differential pattern of neuropsychological impairment when studied in an early stage of dementia and with a mild degree of severity. Such patterns might be of value for the development of clinical diagnostic criteria.     

Nuclear magnetic resonance imaging and single photon emission tomography with radio-iodine labelled compounds in the diagnosis of dementia

White matter lesions and T1 changes were identified using NMR and then compared between groups of patients suffering from dementia of the Alzheimer type (DAT), Multiple infarct dementia (MID) and normal controls. All DAT and MID patients were also imaged with a gamma camera using 123Iodo-n-isopropyl-amphetamine, a radiopharmaceutical whose uptake in the brain follows the regional blood flow. While NMR was not able to differentiate between DAT and MID, 19 out of 21 DAT patients compared to four out of 18 MID patients showed bilateral parietal lesions on IMP scans.     

Neuroendocrine measures of dopaminergic function in chronic cocaine users

Plasma prolactin (PRL) and growth hormone (GH) levels are determined, in part, by the effects of dopamine (DA) at pituitary and hypothalamic DA receptors, respectively. To determine if chronic cocaine abuse alters dopaminergic activity, basal PRL and GH concentrations were measured in 16 male patients meeting DSM-III-R criteria for cocaine dependence (8 cocaine users and 8 cocaine + alcohol users) and 8 normal controls. In addition, the functional responsivity of DA receptors was assessed in the same group of patients by measuring the change in plasma PRL and GH concentrations following the administration of the direct-acting DA agonist, apomorphine (0.01 mg/kg, s.c.) or saline. No difference in basal plasma PRL and GH levels or plasma PRL and GH responses to apomorphine administration was found between the entire group of cocaine patients and normal controls. However, three of the cocaine patients had basal plasma PRL levels that were more than 2.5 SD greater than that of the normal controls, suggesting that some interference of dopaminergic inhibition of PRL secretion might be present in at least some cocaine users. Although baseline plasma PRL levels were elevated in a subgroup of cocaine users, these data do not support the hypothesis that chronic cocaine abuse produces consistent abnormalities in dopaminergic function at the pituitary or hypothalamus.     

Multi-infarct dementia: a computed tomographic study

CT Scan of 30 patients with multi-infarct dementia (MID) were compared with age- and sex-matched controls. Infarcts were seen in 93% of MID cases and 10% of controls. A marked difference in the occurrence of white matter low attenuation was seen between the groups. All the parameters of cerebral atrophy studied showed a statistically significant correlation with the presence of dementia.     

Quantified-EEG in normal aging and dementias

The value of quantitative electroencephalography (q-EEG) in the differential diagnosis of multi-infarct dementia (MID) and dementia of Alzheimer's type (DAT) is controversial. To evaluate the possible diagnostic role of q-EEG in these two conditions we studied 18 healthy adults, 16 healthy elderly (HE), 29 DAT patients and 45 MID patients. MID patients showed a significant increase of delta activity on the occipital regions, a significant widespread increase of theta activity, a significant widespread decrease of alpha activity. DAT patients showed a significant widespread increase of delta and theta activity, a significant widespread decrease of alpha activity. Spectral profile analysis showed an asymptotic exponential peak frequency at 4.33 HZ, and the disappearance of dominant activity in DAT patients; a 1 Hz decrease of peak frequency with a preserved normal profile in MID patients. We conclude that q-EEG is a useful ancillary test to differentiate MID from DAT.     

多梗塞性痴呆和Alzheimer型痴呆的SPECT和MRI比较研究

对２２例多梗塞性痴呆，１５例Ａｌｚｈｅｉｍｅｒ型痴呆病人和２４例同龄，同利手健康对照组作了单光子发射计算机断层显角和磁共振成象检查。结果发现ＳＰＥＣＴ在ＭＩＤ病人主要表现为多发性，局灶性脑放射性减低，两侧不对称，以额皮质，皮质下明显；ＤＡＴ病人主要表现为大脑皮质放射性对称性降低，以颞顶枕明显。     

Neuropsychiatric aspects of multi-infarct dementia and dementia of the Alzheimer type

Delusions, depression, and hallucinations were assessed in 30 patients with dementia of the Alzheimer type (DAT) and 15 with multi-infarct dementia (MID). The nature and prevalence of delusions did not distinguish DAT from MID: delusions were present at the time of examination in 30% of patients with DAT and in 40% of patients with MID, and had occurred at some time in the course of the illness in half the patients of each diagnostic group. Delusions were primarily paranoid in type and involved elementary misbeliefs concerning theft or infidelity. Depression was significantly more common in MID than DAT. Seventeen percent of patients with DAT had depressive symptoms; none with severe depression were identified. Four of 15 patients with MID exhibited major depressive episodes and 60% manifested depressive symptoms. Depression and delusions were not deducted in patients with severe dementia. Hallucinations occurred in both diagnostic groups but were not common: one patient with DAT and one with MID had auditory hallucinations, and three patients with MID had visual hallucinations.     

Course characteristics in the differentiation of dementia of the Alzheimer type and multi-infarct dementia

Clinico-pathological studies have shown that the clinical diagnosis of multi-infarct dementia (MID) is even more difficult than that of dementia of the Alzheimer type (DAT). The study evaluated the significance of course characteristics for the diagnosis of MID and DAT. Course characteristics were rated when 57 demented patients were admitted to our neurogeriatric department. Diagnosis of MID and DAT, respectively, was established after a follow-up study with repeated neurological, psychiatric and neuropsychological investigations. In 21 cases diagnosis was confirmed by postmortem neuropathology. MID lacked the typical course of the disease in about two thirds of patients, while most DAT patients presented with the typical course of primary degenerative dementia. Features of the "typical" clinical course of MID (abrupt onset, stepwise deterioration) helped to exclude DAT, whereas MID could not be excluded on the basis of a history of insidious onset and gradual decline.     

HIGH PROPORTION OF DEMENTIA WITH LEWY BODIES IN THE POSTMORTEMS OF A MENTAL HOSPITAL IN GERMANY

Objective. Dementia with Lewy bodies (DLB) is under-recognized in Germany. No data on the number of patients suffering from this condition in Germany are available at present. We were interested in the proportion of DLB in the postmortems of demented inpatients in the care of a psychogeriatric service. Design. In a retrospective study we examined consecutive postmortems of inpatients who died in one mental hospital. Setting. A suburban and rural old age psychiatry service in Germany. Patients. 103 consecutive postmortems had been performed from 9/1987 to 6/1995. Fifty-nine (57.3%) of all cases warranted the clinical diagnosis of dementia (DSM-III-R). Measures. The causes of dementia were examined histologically. Lewy bodies (LBs) were detected with ubiquitin immunohistochemistry. Results. DLB was the third most frequent cause of dementia (13.6% of demented), after dementia of Alzheimer's type (DAT) (35.6%) and mixed DAT and vascular dementia (15.3%), but ahead of ‘pure’ vascular dementia (MID). The DLB group showed a male preponderance compared with the DAT, MID and mixed group of our series. The DLB patients died younger than the DAT patients. The differences, however, were not statistically significant. All DLB cases showed neurofibrillary and amyloid pathology sufficient to warrant an additional diagnosis of DAT. Cases with ‘pure’ LB pathology had not been detected in our series. Conclusions. Our results indicate that by using appropriate methods, ie ubiquitin immunohistochemistry, a considerable number of DLB cases can be detected in postmortems of demented patients from German mental hospitals. © 1997 by John Wiley & Sons, Ltd.     

Platelet MAO-B activity and the psychopathology of Parkinson's disease, senile dementia and multi-infarct dementia

Monoamine oxidase-B (MAO-B) activity of platelets of an age- and sex-matched group of controls was compared with several groups of inpatients having non-familial dementia of Alzheimer type (DAT), Parkinson's disease (PD), multi-infarct dementia (MID), mixed types of these 3 diseases and a group of other central nervous system (CNS) organic disorders. All patients were subjected to several psychometric tests, including the Sandoz Clinical Assessment--Geriatric Scale, Hamilton Rating Scale for Depression, Mini-Mental State Examination and the Organic mental Disorder Scale (OMDS). A statistically significant enhancement of MAO-B activity could be observed in DAT patients and in PD patients, whereas the MID group showed a mean activity similar to that of the control group and the group with other organic CNS disorders. In DAT patients the degree of dementia in the OMDS test and the enhancement of MAO activity were positively correlated, but PD did not show such a correlation. It is concluded that the increase of MAO activity in PD and in DAT might be due to a disease-related enhanced affinity to oxygen and to such oxygen-derived radicals as superoxide or hydroxyl radicals. However, a possible drug-induced enhancement of MAO activity in PD cannot be excluded. Furthermore, the MAO-B activity values in platelets of individual patients or controls are not indicative of diagnosis or prognosis of any of these diseases and are of no disease-related specificity.     

Growth hormone (GH) and prolactin responses after GH-releasing hormone in major depressive disorder: relationship to somatomedin C levels and dexamethasone suppressibility of cortisol

To explore the growth hormone-releasing hormone (GHRH)-GH-somatomedin axis in major depressive disorder, 12 patients and 12 normal controls matched to the patients on age, sex, ovarian status and body weight received synthetic human GHRH-44 amide (1 microgram/kg) as an intravenous bolus. Compared to controls, the depressed patients showed a reduction in baseline plasma GH and a significant attenuation of net plasma GH responses to GHRH. The blunted GH responses occurred along with significantly increased somatomedin C (Sm-C) concentrations. The impairment of GH responses to GHRH and the increased Sm-C concentrations in patients with depression could have resulted from episodic hypersecretion of GH during the daytime, indicating integrity of the negative feedback circuitry. Normal feedback regulation suggests that diurnal episodic hypersecretion of GH reflects an abnormality at or above the level of the hypothalamus, so that the GHRH-GH-somatomedin axis hyperactivity observed in certain patients with major depressive disorder may be due, at least in part, to hypersecretion of hypothalamic GHRH. Our failure to demonstrate a difference in plasma prolactin (PRL) responses to GHRH between controls and depressed patients indicates that GHRH is not a PRL releaser in patients with major depression and that the altered GH secretory dynamics may not be directly related to the altered circadian PRL secretion linked to depression.     

Endocrine responses to growth hormone releasing hormone and corticotropin releasing hormone in early-onset Alzheimer's disease

In a study of the hypothalamic-pituitary-somatotropic (HPS) and the hypothalamic-pituitary-adrenal (HPA) systems in early-onset Alzheimer's disease (AD), 10 drug-naive patients and matched controls were given 50 micrograms growth hormone releasing hormone (GHRH) at 9 a.m. and 100 micrograms corticotropin releasing hormone (CRH) at 6 p.m. as an i.v. bolus dose. Compared with controls, patients with AD showed attenuated GHRH-induced growth hormone (GH) responses and decreased adrenocorticotropic hormone (ACTH) but normal cortisol secretion following CRH. GH responses to GHRH were negatively correlated with the plasma insulin-like growth factor (IGF-I) concentrations and the severity of dementia. A positive correlation was found between GHRH-evoked GH release and ACTH responses to CRH. The results suggest a pathological process at the level of the pituitary or the hypothalamus, possibly involving a cholinergic, monoaminergic, or peptidergic imbalance in AD, and support the view that altered HPS and HPA secretory dynamics in AD are related to the underlying brain dysfunction.     

CSF cholinesterase in early-onset and lateonset Alzheimer's disease and multi-infarct dementia of Chinese patients

Using Ellman spectrophotometric method we measured the total cholinesterase (ChE) activity in lumbar cerebrospinal fluid (CSF) of 13 persons without neurological disorder, 10 non-demented patients with cerebral infarcts, 17 patients with dementia of Alzheimer's type (DAT) (11 presenile, 6 senile cases), 10 patients with multi-infarct dementia (MID), 1 patient with Parkinson's disease associated with dementia. The ChE activity in CSF was significantly lower in the DAT group compared with age-matched control subjects (p<0.001). This paper also analyses the possibility of using CSF ChE activity as a marker of DAT, and the relationships between its level of activity and the age of the patient at onset, stage of illness and severity of dementia as well as discrepancies in the data published so far. Previous work has shown that ChE activity in the brain tissue and CSF of MID is normal: therefore, if low ChE activity is found in the CSF of MID patients, as was obtained in 8 out of 10 cases in our series, the diagnosis of mixed dementia should be considered.     

Effect of calcium channel antagonist (nicardipine) on growth hormone and prolactin secretion in pituitary adenomas

This study was designed to investigate the effect of calcium channel antagonist (nicardipine) on basal and bromocriptine-inhibited GH or PRL secretion in eight patients with pituitary adenomas (six GH producing adenomas and two prolactinomas). GH or PRL was measured in blood collected at intervals for 12 hours after oral administration of nicardipine (Nc) (40 mg) and/or bromocriptine (Br) (2.5 mg) in each case. In vitro, pituitary adenoma cells were incubated in media containing Nc (200 ng/ml) and/or Br (200 ng/ml) over a 72-h period, and then in drugs-free media for three days. Media were collected at 24-h intervals and assayed for GH or PRL. In three of six GH producing pituitary adenomas, GH secretion was inhibited by Nc both in vivo and in vitro. In prolactinomas, PRL secretion was inhibited by Nc in vitro, but in vivo, an increase of plasma PRL levels was observed after Nc administration in one of two cases. In two acromegalic patients and one patient with prolactinoma, Nc reduced the suppression of GH or PRL secretion induced by Br. These findings indicate that influx of extracellular calcium plays an important part in both GH and PRL secretion in functioning pituitary adenomas, and that Nc effects on GH and PRL secretion in pituitary adenomas by blocking of influx of calcium and/or antidopaminergic action. It is considered that the combined administration of calcium channel antagonist (Nc) and Br for acromegalic patients and administration of Nc for patients with prolactinomas should be avoided.     

GROWTH HORMONE SECRETION IN PRIMARY DEGENERATIVE DEMENTIA: CORRELATIONS WITH COGNITIVE IMPAIRMENT

Changes in brain peptides and neurotransmitters are thought to elicit alterations of growth hormone (GH) secretion in dementia. Baseline GH levels and hormone responses to GH-releasing hormone (GHRH)—administered alone or after pyridostigmine pretreatment—were evaluated in 17 patients, aged 52–83, with primary degenerative dementia quantified by the Clinical Dementia Rating (CDR) Scale and the Mini-Mental State Examination (MMSE) with a view to detecting correlations between neuroendocrine and clinical data. Basal GH levels were not statistically different in patients and in age-matched controls. However, when patients were split into the three CDR groups of disease severity, basal GH levels were significantly higher in those with more severe dementia than in all other patients and in controls. GH responses to GHRH, evaluated both in terms of peaks attained after simulation and of secretion areas under the curve (AUC), were significantly higher in patients than in controls after pyridostigmine pretreatment, but not after the infusion of GHRH alone. Patients with mild to moderate dementia had GH peaks after GHRH higher than more severe patients. Pyridostigmine did not potentiate GHRH effects in the more severe cases. The scores on Rey's 15-word test for memory function were directly correlated with GH peaks after GHRH. No correlations were found between GH data, age, body weight, disease duration and scores at other psychometric assessments such as MMSE, Raven's matrices, verbal fluency or WAIS tests.     

EEG findings in senile dementia and normal aging

EEG findings in 62 patients with senile dementia of Alzheimer type (SDA), 22 patients with multi-infarct dementia (MID) and 90 controls of same age and sex were studied. The SDA patients differed significantly from the controls in EEG normality, over-all disturbance, dominant occipital rhythm, accentuation of theta and delta, fluctuations in alertness, paroxysmal activity and H-reaction. Even the least severely affected SDA patients differed significantly from the controls in all EEG variables except paroxysmal activity. With increasing degree of intellectual impairment in the SDA group the dominant occipital rhythm became slower.
The MID group differed from the controls in all EEG parameters including asymmetric findings. The EEG findings of the SDA patients differed significantly from those of the MID patients only in asymmetric findings which were more common in the MID patients.
29 % of the normal elderly people had EEG alterations. Abnormalities were mild. Asymmetric findings, mainly theta activity in left temporal region were common. H-reaction (occipital driving response ± 18 c/s) was well preserved in the controls.
EEG is valuable in differentiation of dementia patients from normal elderly people, but differentiation between MID and SDA is not reliable by using EEG, only.