Lars Gustafson

Frontal lobe degeneration of non-Alzheimer type. II. Clinical picture and differential diagnosis☆

In a longitudinal prospective study of dementia, 158 patients were investigated post mortem. Sixteen patients were classified as frontal lobe dementia (FLD) of non-Alzheimer type and four cases as Picks disease. Positive heredity for dementia was reported in 50% of these cases compared to 30% in a reference group of patients with Alzheimers disease (AD). The typical clinical picture in FLD and Picks disease was that of a slowly progressive dementia, at an early stage dominated by personality change, lack of insight, disinhibition, and later on stereotypy and increased apathy. There was also a progressive dynamic aphasia ending in mutism and amimia. Memory and spatial functions were comparatively spared. Disinhibition, oral/dietary hyperactivity, and echolalia were more consistently found in Picks disease compared to FLD. The differential diagnosis against AD, cerebrovascular dementia, and other degenerative dementias and against affective disorders and psychotic reactions are discussed.

Clinical Picture of Frontal Lobe Degeneration of Non-Alzheimer Type

Frontal lobe degeneration of non-Alzheimer type (FLD) is the second most common primary degenerative dementia in southern Sweden. Clinical findings in 30 FLD cases with postmortem-verified diagnoses are described. FLD starts in the presenium with a mean disease duration of 7.5 years (range 3-17 years). Clinical onset is insidious and slow and the early stage is dominated by personality changes with lack of insight and judgement and signs of disinhibition. A typical feature is progressive loss of expressive speech with stereotyped phrases, late mutism and amimia. Restlessness, changes of oral/dietary behavior and utilization behavior are prevalent as also psychotic features. Temporal and spatial orientation are usually preserved for a long time in contrast to Alzheimers disease. Dementia in FLD is similar to that of Picks disease and ALS with dementia. Early recognition of FLD seems possible based on standardized clinical evaluation supported by neuropsychological tests, measurement of regional cerebral blood flow and other types of brain imaging. The etiology of FLD is unknown but a positive heredity was reported in 60%.

The Swedish Centenarian Study: A Multidisciplinary Study of Five Consecutive Cohorts at the Age of 100

Centenarians born 1887–91, who lived in southern Sweden were asked to participate in this multidisciplinary study (N = 164). Of the survivors (N = 143), 70 percent agreed (N = 100). The purpose was to describe the population from physical, social, and psychological points of view; to characterize centenarians with various health conditions and diverse degrees of autonomy and life satisfaction; and to identify factors at 100 years that predict future survival. Results: Eighty-two percent were women, 25 percent lived in their own home, 37 percent in old age homes, and 38 percent in nursing homes. Socioeconomic status showed a similar distribution compared to nationally representative data. Fifty-two percent managed activities of daily living with or without minor assistance. The incidence of severe diseases was low. In 39 percent a disorder of the circulatory system was found. Thirty-nine percent (women) and 11 percent (men) had had at least one hip fracture. Twenty percent had good hearing and good vision. Twenty-seven percent were demented according to DSM III-R criteria. Means on cognitive tests (word-list, digit-span, learning, and memory) were lower compared to seventy to eighty year old groups. The variation in performance was extremely widespread. Personality profiles (MMPI) indicated that the centenarians were more responsible, capable, easygoing and less prone to anxiety than the population in general. Extensive neuropathological investigation revealed no major diseases or large lesions but mild though multiple changes. Results suggest that centenarians are a special group genetically. A causal structure model emphasized body constitution, marital status, cognition and blood pressure as particularly important determinants for survival after 100 years.

REGIONAL CEREBRAL BLOOD FLOW IN ORGANIC DEMENTIA WITH EARLY ONSET

A few years after the development of the nitrous oxide technique in 1945 by Kety and Schmidt ( l ) , it was established that organic dementia, like other states of impaired function of the central nervous system, is accompanied by a reduction of the total mean cerebral oxygen uptake and blood flow (2 , 3 ) . This was later confirmed with the Lassen-Munck modification of the same method (4), and also by the 13”Xenon clearance method in measurements of the hemisphere flow ( 5 , 6). In bilateral studies it was also shown that the reduction of the cerebral metabolism and blood flow in organic dementia appeared to be most pronounced in the dominant hemisphere, a finding suggesting a “focal” nature of the pathological process underlying organic dementia ( 7 ) . In the investigation presented here, a multi-detector regional cerebral blood flow (rCBF) technique was used to study whether the cerebral circulatory abnormality in organic dementia with early onset is of a diffuse nature, or whether it shows “focal” characteristics related to the psychic symptoms. Another problem which was considered was the relation, if any, between the cerebral blood flow changes and the typical regional distribution of the patho-anatomical changes which are found in presenile dementia of the Alzheimer type (8, 9). This is a first account of the general findings in 38 patients in whom symptoms of dementia had appeared early, i. e. within the fourth or fifth decade. They were referred to one of the three following groups, the Alzheimer group, the “cerebrovascular”group, and a group of other cases (see below). In this paper some general differences between these groups are considered, but the main emphasis is placed on the multi-detector rCBF technique. The clinical part of the study is not yet finished, and it is therefore not possible to include a final discussion of the rCBF data related to the symptomatology,

Intravenous physostigmine treatment of Alzheimer's disease evaluated by psychometric testing, regional cerebral blood flow (rCBF) measurement, and EEG.

Ten patients with Alzheimers disease were treated with intravenous infusion of physostigmine for 2 h. The acute effects on cognitive function, regional cerebral blood flow, and EEG were compared to placebo (isotonic glucose) using a double-blind cross-over design. Physostigmine causes a limited improvement of psychomotor performance and EEG and an increase of blood flow in the most severely affected cortical areas, predominantly in an early phase of Alzheimers disease.

Effects of clinical supervision on nurse-patient cooperation quality - A controlled study in dementia care.

An intervention consisting of individualized planned care for patients and regular clinical systematic supervision for nurses was carried out on a ward for dementia care (the experimental ward, EW). On a similar control ward (CW), no changes were made. Observations of nurse-patient cooperation during morning care were collected at both wards, before and during the intervention. The observations (N = 107) were analyzed blindly and sorted into already-developed categories. The distribution of the cooperation-style categories was then analyzed statistically. The patients who survived throughout the study period (N = 18) were also compared over time. Nurse-patient cooperation at the EW improved significantly during the intervention period, whereas, at the CW, it deteriorated (p = .02). Status of surviving patients followed the same pattern (p = .001). The findings indicate that such interventions can improve the quality of nurse-patient cooperation in dementia care.

EEG and cognitive impairment in presenile dementia.

EEG and psychometric findings were studied in a group of 57 patients consisting of 19 cases of Alzheimers disease, 7 cases of Picks disease, 24 cases of cerebrovascular dementia (CVD) and a group of 7 cases with dementia of various other etiology. The diagnoses have so far been confirmed by autopsy in 23 out of 57 cases. EEG was evaluated by means of visual inspection. Psychometric studies enabled a classification into 5 psychometric defect groups according to the degree of dementia. An overall good correlation was found between the degree of dementia and EEG abnormality. A significant correlation between the test score and the EEG was found only for the vocabulary test and paired associates test. However, on the reaction time test, color word test, and Kohs block design test, large patient groups were untestable, and a highly significant correlation was found between non‐testability and severely abnormal EEG. The Alzheimer and the CVD groups differed distinctly, most of the Alzheimer cases showing a severe or moderate degree of EEG abnormality and dementia, whereas in the CVD cases, the dementia was less pronounced and the EEG often normal or only slightly abnormal. Four out of seven cases of Picks disease had a normal EEG, which distinguished them from the Alzheimer cases which had a comparable psychometric defect.

Recovery in hydrocephalic dementia after shunt operation.

Twenty-three patients with hydrocephalic dementia were studied before and after shunt operation, and improvement was found in 12. Before operation, the improved cases showed more symptoms of confabulation, gait disturbance, urinary incontinence, lack of insight, and constructional apraxia. The improvement was also most marked in these symptoms. The significance of general versus specific symptoms, duration, and aetiology is discussed from a differential diagnostic standpoint, and we conclude that the adequate and early diagnosis of hydrocephalic dementia is essential for good outcome after shunt operation, and that psychiatric and psychometric evaluation enable such a diagnosis to be made.

Apolipoprotein E genotyping in Alzheimer’s disease and frontotemporal dementia

Alzheimers disease (AD) and frontotemporal dementia (FTD) are characterized by progressive neuronal loss and microvacuolization, although with different distributions of cortical involvement. In contrast to AD there is no amyloid, senile plaques or tangles in FTD. The involvement of chromosome 19 in AD has been associated with apoliprotein E (ApoE) and the epsilon 4 gene frequency has been related to increased risk and early onset of AD. Our analysis of frequency of the ApoE alleles in 38 patients with AD, 21 patients with FTD and 29 normal controls indicates an association of both AD and FTD with an increased frequency of the epsilon 4 allele and in AD also with homozygosity for epsilon 4. Our results might indicate that ApoE epsilon 4 is an important aggravating and pathoplastic factor in the presence of genetic and other determinants for the development of AD or FTD. A significantly higher epsilon 2 frequency in our FTD material compared to AD and normals might also indicate a connection with the distribution of cortical degeneration.

Frontotemporal Dementia Can Be Distinguished from Alzheimer’s Disease and Subcortical White Matter Dementia by an Anterior-to-Posterior rCBF-SPET Ratio

Sixteen patients with frontotemporal dementia (FTD), 27 with early-onset Alzheimer’s disease, 25 with late-onset Alzheimer’s disease, 19 with subcortical white matter dementia (SWD) and 28 normal controls underwent semiquantitative regional cerebral blood flow measurement (rCBF) using single-photon emission tomography (SPET; 99mTc-HMPAO) and either computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain. An anterior-to-posterior rCBF-SPET ratio (mesial superior frontal gyrus/medial temporal lobes) was calculated, which significantly separated the FTD group from the other dementia groups and controls with a sensitivity of 87.5% and a specificity of at least 78.6%. CT/MRI was found to be helpful in the differential diagnosis between FTD and SWD. In FTD patients, the mesial superior frontal gyrus, near the polus frontalis, was found to be the region with the most reduced rCBF values.