Showing papers in "Dementia and Geriatric Cognitive Disorders in 1998"
TL;DR: It is concluded from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol.
Abstract: Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer's disease. We have treated 3 patients with Alzheimer's disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.
436 citations
TL;DR: A description of the B-ADL and its application is focused on, thought especially suitable for application within a GP and primary care context for both screening a patient’s ADL capacities as well as for documentation of treatment effects and the progress of dementia.
Abstract: The Bayer Activities of Daily Living Scale (B-ADL) has been developed on an international basis to assess deficits in the performance of everyday activities The scale's main target group is community dwelling patients who suffer mild cognitive impairment or mild-to-moderate dementia It comprises 25 items and takes the form of a questionnaire to be completed by a caregiver or other informant sufficiently familiar with the patient Statistical, clinical and domain-related criteria were used to select items from among a large number of activities of daily living (ADL) questions field tested in pilot studies in the USA, Germany, UK, Russia and Greece The items included in the B-ADL have been chosen for their sensitivity to cognitive impairment, simplicity of concept, international applicability and their relevance to patients coping with the demands of everyday life The scale uses items which reflect a wide range of domains On account of its brevity, it is thought especially suitable for application within a GP and primary care context for both screening a patient's ADL capacities as well as for documentation of treatment effects and the progress of dementia This paper focuses on a description of the scale and its application
390 citations
TL;DR: Although the progressive amnestic form of AD is the most common presentation, other variations on the clinical syndrome can be important to identify because they may have implications for prognosis and treatment.
Abstract: Alzheimer''s disease (AD) can present as a variety of clinical profiles. Although the most common presentation is that of a progressive amnestic disorder with subsequent involvement of other cognitive
226 citations
TL;DR: For diffuse white matter pathology of similar appearance in vascular and neurodegenerative disease with dementia, there may be various at least partly contrasting aetiologies, which can be differentiated by the presence of even minor focal lesions in some cases.
Abstract: Morphological white matter changes were investigated in clinically and neuropathologically diagnosed cases of Alzheimer's disease (AD; 60 cases) and vascular dementia (VaD; 40 cases). In 33 of 60 AD cases, a white matter disease (WMD) characterized by tissue rarefaction, mild gliosis and a non-amyloid small-vessel sclerosis occurred in the central, preferentially frontal deep white matter. The mean vessel density was significantly lower than in normal control case frontal white matter. The presence of WMD did not parallel the severity of grey matter Alzheimer encephalopathy. In 25 of 60 AD cases, white matter degeneration with signs of both condensation and rarefaction of tissue elements was seen subjacent to advanced cortical degeneration in the temporal lobes. It concurred with WMD in only 13 cases and was judged to be of anterograde, Wallerian type and not related to angiopathy. In VaD, similar changes occurred, accompanied by several types of focal and topographically related lesions. For diffuse white matter pathology of similar appearance in vascular and neurodegenerative disease with dementia, there may be various at least partly contrasting aetiologies, which can be differentiated by the presence of even minor focal lesions in some cases. For the recognition of such subtle variations in the spectrum of WMD, modern imaging techniques are crucial for detailed clinical diagnosis and attempts at therapeutic intervention.
211 citations
TL;DR: Correlative histopathologic findings show hyperintense periventricular capping of the frontal horns to reflect predominantly a specific anatomic situation characterized by loosely arranged fine-fiber tracts with low myelin and high extracellular fluid content.
Abstract: Magnetic resonance imaging (MRI) has dramatically enhanced our capability of detecting age-related changes of the brain even before they become clinically apparent. Among those are preferentially alte
180 citations
TL;DR: Vascular risk continues to be of importance in the oldest age groups, based on incident cases of dementia in a population aged 75 and over based on informants of the respondents with incident dementia.
Abstract: The contribution of vascular pathology to the manifestation of dementia and the importance of vascular risk to measures of cognitive function is being increasingly recognized. In particular, confirmation of this risk points towards approaches for prevention in large sections of the population. Information on determinants of incident dementia is increasing, but still relatively few studies of risk have been based on incident cases of dementia in very elderly populations. In this study based on incident cases of dementia in a population aged 75 and over, vascular risks were obtained from informants of the respondents with incident dementia. When compared with controls the factors associated with incident dementia were history of heart attack (odds ratio 2.9), transient ischaemic attacks (4.8), cerebrovascular accidents (3.4), family history of first-degree relatives with dementia (4.0), and occupational exposure to vibrating instruments (1.4). If only Alzheimer's disease, clinically diagnosed, was included, diabetes (1.4) and a history of dementia in first-degree relatives (6.6) emerged. Thus, vascular risk continues to be of importance in the oldest age groups.
155 citations
TL;DR: Comparison with other studies suggests that dementia of all types is as frequent in Assiut governorate as elsewhere.
Abstract: The aim of this study was to determine the prevalence rate of Alzheimer’s disease (AD) and other types of dementias among the population over the age of 60 years in Assiut governorate. A 3-phase cross-sectional population-based study was carried out to screen 2,000 subjects residing in 11 different locations representing the sociocultural status of the area. We subjected each proband to a modified form of the Mini Mental State Examination test. Subjects scored 21 or less were investigated according to a standardized protocol. We found 90 demented subjects yielding a crude prevalence ratio (case per 100 population over the age of 60) of 4.5. A diagnosis of subtypes of dementia was reached in 83 cases. Prevalence ratios for dementia subtypes were 2.2 for AD, 0.95 for multi-infarct dementia. 0.55 for mixed dementias and 0.45 for secondary dementias. Age-specific prevalence tends to be doubled every 5 years. Occupation, level of education and residence did not affect the prevalence or severity of dementia. Comparison with other studies suggests that dementia of all types is as frequent in Assiut governorate as elsewhere.
111 citations
TL;DR: The association between WMLs and hypertension may be mediated through several different pathogenetic pathways, and the renin-angiotensin system is an example of a system that may be involved in the pathogenesis of both hypertension and arteriosclerosis.
Abstract: Hypertension or high blood pressure is constantly reported to be the main risk factors for ischaemic white matter lesions (WMLs). These lesions show the histopathological picture of diffuse demyelination and moderate loss of axons in subcortical structures. The main hypothesis regarding the association between high blood pressure and ischaemic WMLs is that long-standing hypertension causes lipohyalinosis of the media and thickening of the vessel walls with narrowing of the lumen of the small perforating arteries and arterioles which nourish the deep white matter. Episodes of hypotension may then lead to hypoperfusion and hypoxia-ischaemia in the white matter. In line with this, low blood pressure has also been reported to be a risk factor for WMLs. However, also other pathogenetic mechanisms may be involved. Hypertension may cause disturbances in the blood-brain barrier, which may cause lesions in the white matter by cerebral oedema, by activation of astrocytes or by destructive enzymes or other poisons which pass through the damaged vessel walls. The renin-angiotensin system is an example of a system that may be involved in the pathogenesis of both hypertension and arteriosclerosis. Its effector peptide angiotensin II has several blood-pressure-increasing effects, such as direct vasoconstriction and activation of the sympathetic nervous system. It also promotes hyperplasia and hypertrophy in vascular smooth muscle cells. Recently an association between hypertension and Alzheimer's disease has been reported. It is not clear whether this may be the reason for the common occurrence of WMLs in cases of late-onset Alzheimer's disease, as Alzheimer's disease may also cause lesions in the cerebral microvasculature. The association between WMLs and hypertension may thus be mediated through several different pathogenetic pathways.
99 citations
TL;DR: Results from a drug withdrawal study suggested that propentofylline does not merely relieve dementia symptoms but slows the progression of the disease itself, and was found to provide consistent improvements over placebo in efficacy assessments for both AD and VaD patients.
Abstract: Propentofylline, a neuroprotective glial cell modulator, has been shown in preclinical studies to address some of the common pathological processes of Alzheimer's disease (AD) and vascular dementia (VaD), including glial cell activation and increased production of cytokines, free radicals, and glutamate. To examine whether propentofylline (300 mg t.i.d. taken 1 h before meals) would provide beneficial effects in patients with AD and/or VaD, 901 patients with mild-to-moderate AD and 359 patients with mild-to-moderate VaD were enrolled in four double-blind, placebo-controlled, randomized studies ranging in duration from 6 months to 56 weeks. Propentofylline was found to provide consistent improvements over placebo in efficacy assessments for both AD and VaD patients. In addition, results from a drug withdrawal study suggested that propentofylline does not merely relieve dementia symptoms but slows the progression of the disease itself. Propentofylline had a good safety profile and was generally well tolerated.
93 citations
TL;DR: None of the clinical diagnostic criteria is satisfactory, including the NINCDS/ADRDA ‘possible’ and ‘probable dementia of the Alzheimer type’ (DAT) categories, making these criteria unsuitable for diagnostic purposes in clinical practice.
Abstract: In this study we analysed the accuracy of two sets of clinical diagnostic criteria, the NINCDS/ADRDA and DSM-III-R, in relation to the currently used pathological diagnostic criteria for Alzheimer’s d
89 citations
TL;DR: The evidence suggests that a unique combination of factors is involved in the pathogenesis of each plaque type and, therefore, supports the hypothesis that the major types of Aβ plaque develop independently.
Abstract: Several types of discrete β-amyloid (Aβ) deposit or senile plaque have been identified in the brains of individuals with Alzheimer's disease and Down's syndrome. The majority of these plaques can be classified into four morphological types: diffuse, primitive, classic and compact. Two hypotheses have been proposed to account for these plaques. Firstly, that the diffuse, primitive, classic and compact plaques develop in sequence and represent stages in the life history of a single plaque type. Secondly, that the different Aβ plaques develop independently and therefore, unique factors are involved in the formation of each type. To attempt to distinguish between these hypotheses, the morphology, ultrastructure, composition, and spatial distribution in the brain of the four types of plaque were compared. Although some primitive plaques may develop from diffuse plaques, the evidence suggests that a unique combination of factors is involved in the pathogenesis of each plaque type and, therefore, supports the hypothesis that the major types of Aβ plaque develop independently.
TL;DR: The results showed significant age effects on the rCMRglc in the fronto-temporo-parietal association cortices and retrosplenial areas, and early-onset patients have a more severe reduction of regional glucose metabolism in the association cortice, while late-ONSet patients show a more prominent metabolic deficit in the paralimbic area.
Abstract: This study assessed 46 patients with Alzheimer's disease and 21 aged controls using positron emission tomography. Repeated analyses using a general linear model examined the effect of age at onset on the pattern of the regional cerebral metabolic rate of glucose (rCMRglc). The results showed significant age effects on the rCMRglc in the fronto-temporo-parietal association cortices and retrosplenial areas. Disease duration, overall cognitive severity or normal aging could not account for the effects. The age effects were delineated as a double dissociation, that is, early-onset patients have a more severe reduction of regional glucose metabolism in the association cortices, while late-onset patients show a more prominent metabolic deficit in the paralimbic area.
TL;DR: It was postulated that reduced oxidative activity of ceruloplasmin in plasma might be either a cause or a consequence of AD and that reduced SOD activity might further add to the oxidative disturbances in AD due to defective cerulplasmin activity.
Abstract: The copper-containing enzyme superoxide dismutase (SOD) is a key enzyme in suppressing the amounts of superoxide anion radicals. Ceruloplasmin, the copper-transporting protein in plasma, also possesse
TL;DR: It is suggested that the genotype of ApoE σ4 is associated with not only AD but also VD and ICVD, and that ApoN E σ 4 plays an important role in the development of dementia andICVD.
Abstract: Apolipoprotein E σ4 allele (ApoE σ4) is associated with Alzheimer’s disease (AD) in familial and sporadic cases, but the associations of ApoE σ4 allele and vascular dementia (VD) and/or ischemic cerebrovascular disease (ICVD) are still controversial To clarify the associations of ApoE polymorphism with AD, VD and ICVD in Japanese, we examined ApoE polymorphism in samples of 255 patients with AD, 87 patients with VD, and 123 patients with ICVD, as compared with 117 age-matched healthy control subjects (CTL) The frequency of the ApoE σ4 allele was significantly higher in the VD group (021), the ICVD group (015) as well as in the AD group (026) than in the CTL subjects (008) These findings suggest that the genotype of ApoE σ4 is associated with not only AD but also VD and ICVD, and that ApoE σ4 plays an important role in the development of dementia and ICVD
TL;DR: It is concluded that qEEG and rCBF examinations employed together are accurate tools to differentiate AD from normal ageing, although a lower degree of accuracy is achieved in mildly demented patients.
Abstract: Forty-two patients with probable Alzheimer’s disease (AD) and 18 elderly healthy controls underwent quantitative EEG (qEEG) and regional cerebral blood flow (rCBF; 133Xe clearance) examinat
TL;DR: No genotype or allele of the polymorphisms examined here seemed to be associated with vascular dementia or with Alzheimer’s disease, total cholesterol and LDL cholesterol levels were lower in Alzheimer”s disease patients than in vascular dementia patients and in elderly controls, and the dementia patients with APOB EcoRI R+R– genotype had higher totalolesterol and cholesterol levels than R-R+ homozygotes.
Abstract: The distribution of three DNA polymorphisms ( Xba I, Eco RI, and I/D) of the apolipoprotein B (APOB) gene, and of the I/D polymorphism of the angiotensin I-convertin
TL;DR: Agitation, particularly physical aggression, may impact caregivers even more than does the cognitive status of the demented patient, and the relationship between psychiatric features of dementia and their impact on caregivers is determined.
Abstract: This study was designed to determine the relationship between psychiatric features of dementia and their impact on caregivers. 35 patient-caregiver pairs were evaluated at two university-affiliated dementia clinics, using standard instruments to rate patient psychiatric features and caregiver burden and depression. There were highly significant correlations between patient agitation and both caregiver burden (r = 0.59, p = 0.0002) and depression (r = 61, p = 0.0001). These associations remained significant after adjusting for multiple demographic and dementia variables. There was no significant association between patient delusions, hallucinations, or depression and caregiver burden or depression. Agitation, particularly physical aggression, may impact caregivers even more than does the cognitive status of the demented patient.
TL;DR: MRI-based volumetry allows differentiation between AD or VD from normal controls and that measurement of cerebellar volume may be of use to separate vascular and degenerative dementia, and it is suggested that the atrophic changes in both dementia groups reflect the selective vulnerability of neuronal structures.
Abstract: Quantitative magnetic resonance imaging (MRI) was used to assess global and regional cerebral volumes in patients with a clinical diagnosis of subcortical vascular dementia (VD) and Alzheimer's disease (AD). Whole brain volume, cerebrospinal fluid volume, volumes of the temporal, frontal and parietal lobes, the cerebellum and the amygdala-hippocampus complex were determined using a personal computer-based software. Seventeen patients with VD, 22 patients with AD and 13 healthy controls were included. Analysis of covariance using age as covariate demonstrated significant mean differences between controls and dementia groups with respect to all morphological parameters. However, apart from the volume of the cerebellum no significant volumetric differences were found between VD and AD. These results indicate that MRI-based volumetry allows differentiation between AD or VD from normal controls and that measurement of cerebellar volume may be of use to separate vascular and degenerative dementia. However, since the distribution of cerebral atrophy in both dementia groups is very similar, it is suggested that the atrophic changes are not specific to the underlying cause but rather reflect the selective vulnerability of neuronal structures.
TL;DR: In this article, the most efficient psychometric predictors of FLD were Digit Symbol, estimation tasks, word list recall, and particularly the FAS word fluency test, and the differences between groups were not related to the degree of dementia, indicating that differences remained during progression of the diseases.
Abstract: Neuropsychological differences between 14 patients with a clinical diagnosis of frontal lobe degeneration of non-Alzheimer type (FLD) and 15 patients with a clinical diagnosis of Alzheimer's disease (AD) were studied. The most efficient psychometric predictors of FLD were Digit Symbol, estimation tasks, word list recall, and particularly the FAS word fluency test. Behavioral predictors of FLD and AD showed a double dissociation: regression and impulsivity characterized FLD, whereas lack of motivation and slowness were typical of AD. Cognitive and behavioral differences between groups were not related to the degree of dementia, as measured by Mini Mental State Examination, indicating that differences remained during progression of the diseases.
TL;DR: A double-blind, placebo-controlled, 26-week study of the AChE inhibitor metrifonate using the NeuroPsychiatric Inventory to assess the effects of treatment on neuropsychiatric symptoms observed statistically significant mean change differences favouring treatment in the total NPI score and in symptoms of depression, apathy and hallucinations.
Abstract: Preliminary studies suggest that non-cognitive behavioural and personality alterations in Alzheimer's disease may benefit from agents which inhibit central acetylcholinesterase (AChE). A double-blind, placebo-controlled, 26-week study of the AChE inhibitor metrifonate using the NeuroPsychiatric Inventory (NPI) to assess the effects of treatment on neuropsychiatric symptoms observed statistically significant mean change differences favouring treatment in the total NPI score and in symptoms of depression, apathy and hallucinations, as well as a nearly significant difference in aberrant motor behaviours. These data are consistent with previous studies and are believed to represent the first large prospective, controlled study demonstrating a beneficial effect of AChE inhibitor therapy on neuropsychiatric symptoms in Alzheimer's disease. The nature of non-cognitive symptom responses to AChE inhibitor therapy and their potential impact on caregivers is discussed.
TL;DR: An overall index combining demographic, cognitive, electroencephalogram and computed tomography features is a strong predictor of survival in early Alzheimer’s disease.
Abstract: We investigated whether an index based on clinical features, electroencephalogram and computed tomography is useful to predict survival in early Alzheimer’s disease. One hundred and sixty-three consec
TL;DR: Hippocampal CMRglc was not significantly decreased in mild AD, and suggests that the pathophysiology of the hippocampus in AD may be more complex than was previously thought.
Abstract: The purpose of this study was to clarify the changes in hippocampal glucose metabolism in mild Alzheimer’s disease (AD) using positron emission tomography (PET) and 2-(18F)fluoro-2-deoxy-&l
TL;DR: An inter- and intrarater study analysing the reliability of the staging method in thin sections concludes that the adapted staging method is strongly reliable and is recommended for staging purposes in institutions where the preparation of thick sections would be difficult.
Abstract: The staging method proposed by Braak and Braak allows the objective and reliable assessment of Alzheimer-related neurofibrillary pathology. Originally the method was designed for 100-microm thick sections. However, the use of thick sections proved to present difficulties in a routine neuropathology laboratory. In order to adapt the staging method for thin paraffin-embedded sections, we performed an inter- and intrarater study analysing the reliability of the staging method in thin sections. Statistical analysis of the data provided by six independent examiners in two rating sessions reveal kappa values of 0.6-0.8 for both the interrater and the intrarater reliability. The average rate of mistake of the examiners was rarely bigger than a half stage. We conclude that the adapted staging method in thin sections is strongly reliable and we recommend it for staging purposes in institutions where the preparation of thick sections would be difficult.
TL;DR: It was found that in the relatives of AD patients the latencies of N2, P3, N3 components were delayed compared with the age-matched normal controls and the amplitude of the P2, N2 components was increased in the latter.
Abstract: Visual-evoked potentials (VEP) to a flash were studied in the first-order relatives of patients with Alzheimer’s disease (AD) (mean age 38.2 ± 2.6 years) in comparison with the patients (mean age 61.9
TL;DR: Using a population-based data set, the prevalence of cognitive impairment, functional status, principal comorbid conditions and 1-year survival for over 300,000 patients admitted to the nursing homes in five US states is described.
Abstract: Cognitive impairment is associated with an increased mortality in older people. The prevalence and impact of comorbidity on functional status and mortality of demented patients has not been fully elucidated. Using a population-based data set, we describe the prevalence of cognitive impairment, functional status, principal comorbid conditions and 1-year survival for over 300,000 patients admitted to the nursing homes in five US states. Sixty-one percent of patients have some level of cognitive impairment, and this correlates with the degree of physical frailty. Severer cognitive impairment is associated with a higher mortality rate. Yet, patients with cognitive impairment appear to have fewer comorbid conditions and are less likely to receive medications and special treatments than residents with normal cognitive status. Additional studies are needed to understand whether demented patients may paradoxically be considered healthier or, instead, are only neglected.
TL;DR: White matter changes, vascular lesions of the brain and associated Alzheimer pathology, the summation of 2 or 3 of these mechanisms may lead to dementia in stroke patients even when each type of lesion is not severe enough to induce dementia by its own.
Abstract: Stroke patients are more likely to have white matter changes than age- and sex-matched controls. White matter changes are associated with an increased risk of dementia occurring after stroke: they often indicate a higher risk of stroke recurrence and they may lead to slight cognitive impairment. Besides white matter changes, vascular lesions of the brain and associated Alzheimer pathology, the summation of 2 or 3 of these mechanisms may lead to dementia in stroke patients even when each type of lesion is not severe enough to induce dementia by its own.
TL;DR: There is not one unique staging system, that different staging criteria might be appropriate to different research or clinical needs, depending on which part of the temporal course of the disease is of primary interest, and on whether the focus is on cognitive, functional, neurological, behavioral, economic, or other issues.
Abstract: 'Stages', as used in clinical practice and research, are defined, their value described, and criteria are proposed for their evaluation The specific interest is in staging Alzheimer's disease (AD) Two staging systems, one based on the Global Deterioration Scale (GDS) and one based on the Mini-Mental State Exam (MMSE), are compared in terms of these criteria, as an illustration of the process involved We propose that there is not one unique staging system, that different staging criteria might be appropriate to different research or clinical needs, depending on which part of the temporal course of the disease is of primary interest, and on whether the focus is on cognitive, functional, neurological, behavioral, economic, or other issues GDS staging seems a better choice for the later stages of AD when the focus is on functional change MMSE staging seems a better choice for tracking the earlier stages of AD when the focus is on cognitive change
TL;DR: White matter changes whose presence in variants of the two entities, Alzheimer’s disease and vascular dementia, is described in this paper.
Abstract: As there is some overlap between Alzheimer's disease (AD) and vascular dementia (VaD), it can be assumed that some particular features that they have in common are responsible for this overlap. One of the candidates is white matter changes whose presence in variants of the two entities is described in this paper. A common, although much debated, division of AD is into two types, type I usually with early and type II usually with late onset. As to VaD, the division can be based on neuropathological changes and vascular disease mechanisms. In one subtype, 'subcortical white matter dementia', white matter lesions are conspicuous features. The overlap between this subtype and AD type I is small, but the overlap is considerable between the same subcortical subtype and AD type II. In the latter, white matter changes and Alzheimer encephalopathy may interact to produce dementia.
TL;DR: Preliminary evidence suggests that intervention on behalf of caretakers may delay the need for institutionalization of family members with AD.
Abstract: The majority of persons with Alzheimer's disease (AD) are cared for by family members in their home. Research from several studies has shown that these care providers have rates of emotional morbidity three times that seen in age-similar individuals. This paper will review the epidemiological data on the incidence and prevalence of emotional disability in caregivers. It will also review the 11 treatment studies in the literature in which blinded intervention was carried out. Nine of these 11 studies show that intervention was more beneficial than the placebo comparison treatment. Both educational and emotional support were effective. However, when compared with each other, emotional support was more effective; the combination may be more effective than either alone. Preliminary evidence suggests that intervention on behalf of caretakers may delay the need for institutionalization of family members with AD.
TL;DR: Results indicate that possession, and thus expression, of the APOE σ4 allele affects preferentially the inferior temporal lobe, encompassing the hippocampus and amygdala, in AD patients.
Abstract: The apolipoprotein E (APOE) gene σ4 allele is known to be associated with late-onset familial and sporadic Alzheimer’s disease (AD). We assessed the possible relationship between APOE genotypes and morphological or functional changes in AD brains by x-ray computed tomography (CT), magnetic resonance imaging (MRI) and Xe-133 single photon emission CT (SPECT). First, we estimated the change in size of the whole brain and total ventricular system by using two x-ray CT indices, the cerebral index (CI) and ventricular index (VI), respectively. Neither CI nor VI differed significantly among APOE genotypes. Then, we focused on the inferior temporal lobe regions by introducing new MRI indices, the inferior temporal index (ITI), temporal horn index (THI) and infero-medial temporal index (IMTI). We found a significant difference in each MRI index among APOE subgroups; ITI and IMTI were lower, while THI was higher in AD patients with at least one APOE σ4 allele (σ4+ group) than in those without such an allele (σ4– group). Finally, we compared relative regional cerebral blood flow (rCBF) of Xe-133 SPECT among the AD subgroups. Relative rCBF in the cerebral cortex, particularly in the temporal lobe, was lower in the σ4+ group than in the σ4– group. These results indicate that possession, and thus expression, of the APOE σ4 allele affects preferentially the inferior temporal lobe, encompassing the hippocampus and amygdala, in AD patients.