Decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer''s disease as shown by MRI and PET.

OBJECTIVE: To investigate the relation between atrophy of the hippocampus and parahippocampal gyrus (the % hippocampal area) and cerebral metabolic rate for glucose (CMRGlc) in Alzheimer's disease. METHODS: 13 patients with probable Alzheimer's disease by NINCDS-ADRDA criteria (six men; seven women, mean age 71 years, mini mental state 13.8 (SD 4.6)) and age matched controls were studied. T1 weighted MRI (0.5T) images were used for evaluation of the hippocampal area. With a digitiser system, a percentage of the hippocampal area to the brain (the % hippocampal area) was calculated. Eight patients received another T1 weighted MRI (1.5T) for further evaluation of the minimum thickness of the hippocampus. Regional CMRGlc (rCMRGlc) was measured using PET and the FDG technique. RESULTS: The hippocampal area in patients with Alzheimer's disease was significantly lower than that of controls (P < 0.01). All the cortical rCMRGlc values in patients with Alzheimer's disease were lower than those of controls (P < 0.01). A significant correlation (P < 0.05) was found between the % hippocampal area and rCMRGlc in the temporal lobe, temporoparieto-occipital (TPO) region, and frontal lobe in Alzheimer's disease. There was a significant correlation between minimal hippocampal thickness and ipsilateral TPO metabolism on both sides. CONCLUSION: The ipsilateral correlation between hippocampal atrophy and decreased TPO metabolism in Alzheimer's disease suggests a functional relation and the asymmetries show that Alzheimer's disease is an asymmetric disease in its early stages.     

Material-specific memory loss in probable Alzheimer''s disease.

This study extends previous work analysing functional dissociations occurring in patients with Alzheimer's disease (AD) by demonstrating that material-specific memory loss is common. The pattern of neuropsychological dysfunction in 191 patients with probable AD was examined and 13% presented with material-specific memory loss. Thirteen patients had impaired immediate verbal recall, but normal non verbal recall and 12 had impaired non verbal recall and normal verbal memory. These patterns appeared to be related to a specific memory deficit and were probably not secondary to associated cognitive impairments. These data confirm earlier observations that the memory defect in AD can be material-specific, and suggest that these patterns of impairment should be viewed as a focal sparing of function.     

Alzheimer''s disease in a patient with posterior cortical atrophy.

Posterior cortical atrophy (PCA) is characterised by slowly progressive dementia with cognitive and perceptual deficits suggestive of bilateral parieto-occipital disease. A case is reported of a patient with PCA and neuropathological findings consistent with Alzheimer's disease.     

Selective perforant-pathway atrophy in Huntington disease: MRI analysis of hippocampal subfields

Introduction

While individuals with Huntington disease (HD) show memory impairment that indicates hippocampal dysfunction, the available literature does not consistently identify structural evidence for involvement of the whole hippocampus but rather suggests that hippocampal atrophy may be confined to certain hippocampal subregions.

Methods

We processed T1-weighted MRI from IMAGE-HD study using FreeSurfer 7.0 and compared the volumes of the hippocampal subfields among 36 early motor symptomatic (symp-HD), 40 pre-symptomatic (pre-HD), and 36 healthy control individuals across three timepoints over 36 months.

Results

Mixed-model analyses revealed significantly lower subfield volumes in symp-HD, compared with pre-HD and control groups, in the subicular regions of the perforant-pathway: presubiculum, subiculum, dentate gyrus, tail, and right molecular layer. These adjoining subfields aggregated into a single principal component, which demonstrated an accelerated rate of atrophy in the symp-HD. Volumes between pre-HD and controls did not show any significant difference. In the combined HD groups, CAG repeat length and disease burden score were associated with presubiculum, molecular layer, tail, and perforant-pathway subfield volumes. Hippocampal left tail and perforant-pathway subfields were associated with motor onset in the pre-HD group.

Conclusions

Hippocampal subfields atrophy in early symptomatic HD affects key regions of the perforant-pathway, which may implicate the distinctive memory impairment at this stage of illness. Their volumetric associations with genetic and clinical markers suggest the selective susceptibility of these subfields to mutant Huntingtin and disease progression.     

Parkinson's disease is associated with hippocampal atrophy.

Patients with Parkinson's disease (PD) may have hippocampal atrophy compared with controls. We compared hippocampal, and extra-hippocampal volumes between PD, PDD (patients with PD who have mild cognitive impairment or dementia), Alzheimer's disease (AD) and controls using volumetric magnetic resonance imaging (MRI). Participants (10 patients with PD, 10 with PDD, 11 with AD, and 12 control subjects) had an informant interview, neurological examination, and psychometric testing. Established, reliable methods were used to measure the hippocampus, parahippocampal gyrus, temporal, frontal, and parieto-occipital lobes. Correction for intracranial volume was carried out before comparison. There was no age difference between groups (mean age, 74 years). On the Clinical Dementia Rating scale (CDR) cognitive impairment was mild (CDR = 0.5) in the majority of PDD and AD patients. Hippocampal (P < 0.0004) volumes were smaller in the patient groups. Effect sizes compared with the control group were: PD, 0.66; PDD, 1.22; and AD, 1.81. The other volumes did not differ significantly. Among PD and PDD patients, recognition memory (r = 0.54, P = 0.015) and Mini-Mental State Examination scores (r = 0.56, P = 0.01) correlated with left, but not right hippocampal volume. In conclusion, hippocampal volume showed a pattern (Control > PD > PDD > AD) suggesting progressive hippocampal volume loss in PD. Volumetric MRI imaging might provide an early marker for dementia in PD.     

Alzheimer''s disease: neuropathological correlates of cognitive and motor disorders

Correlations between clinical symptoms and changes in brain neuropathology were investigated in 34 patients with Alzheimer's disease, who were compared with 17 non-demented, age-matched controls. The patients were originally found in a community survey of dementia and were followed up prospectively until death. A highly significant correlation emerged between the severity of dementia and the numbers of plaques and tangles in the material as a whole, but no essential difference was found between severely and less severely demented patients. Low brain weight correlated highly with many clinical symptoms and signs and the severity of dementia. A multiple regression model consisting of plaques and tangles in amygdala, gyrus frontalis medius, gyrus angularis, and gyrus temporalis medius, plaques of gyrus rectus, tangles of the hippocampus, gyrus precentralis and gyrus cinguli together with brain weight, emerged to link dementia to neuropathological changes at the level of maximum significance. Dyskinetic movements were associated with damage of several brain areas, implying a multiple etiology.     

Apolipoprotein E in the brain and its role in Alzheimer''s disease.

Recent evidence indicates that apolipoprotein E (apoE) plays a central role in the brain response to injury. The coordinated expression of apoE and its main receptor, the apoE/apoB (LDL) receptor, appears to regulate the transport of cholesterol and phospholipids during the different phases of the reinnervation process. The recent discovery that a peculiar form of apoE, the apoE4, is strongly linked to both sporadic and familial late onset Alzheimer's disease (AD) raises the possibility that a dysfunction of the lipid transport system associated with compensatory sprouting and synaptic remodelling could be central to the AD process. The role of apoE in the central nervous system (CNS) is particularly important in relation to the function of the cholinergic system which relies to a certain extent on the integrity of phospholipid homeostasis in neurons. Recent evidence suggests that apoE4 allele has a direct impact on cholinergic function in AD.     

Coexistence of movement disorders and epilepsia partialis continua as the initial signs in probable Creutzfeldt-Jakob disease.

Movement disorders and epilepsy rarely occur in the early stage of Creutzfeldt-Jakob disease (CJD) but have not been reported concurrently. We report on a 47-year-old patient with probable CJD who presented with generalized chorea and focal dystonia with myoclonic jerks on the right hand. Myoclonic jerks progressed to epilepsia partialis continua within 5 days of admission to the hospital. The diagnosis of our patient was compatible with probable CJD on the basis of clinical course, electroencephalogram, and diffusion-weighted magnetic resonance imaging findings, and presence of 14-3-3 protein in cerebrospinal fluid. To our knowledge, this is the first report of a case developing both movement disorders and epilepsia partialis continua in the early stage of the disease.     

Mental disorders in a female patient with probable Creutzfeldt-Jakob disease

The paper presents an overview of the current knowledge about the etiology, classification of Creutzfeldt-Jakob disease, abnormalities in the results of the EEG, MR and laboratory examinations in patients with this disease. The diagnostic value of the CSF examination for presence of protein 14-3-3 is underlined. The article is based on both Polish and foreign literature, describing mainly the diagnostics of CJD. The case of a female patient with dementia, mental disorders and neurological symptoms in the course of probable CJD, who was hospitalized at the Psychogeriatric Department of the Neuropsychiatric Hospital in Lublin is described.     

Detection of hippocampal atrophy in patients with temporal lobe epilepsy: A 3-Tesla MRI shape

In patients with mesial temporal lobe epilepsy (MTLE), brain MRI often detects hippocampal sclerosis (HS). Almost half of patients with MTLE do not show any hippocampal damage on visual or volumetric assessment. Here, we wished to prospectively assess 65 patients with MTLE (41 women, mean age: 39 ± 10 years, range: 21–69; right (12/65 patients) (MRI-negative) nMTLE; right (14/65 patients) (MRI-positive with HS) pMTLE; left (24/65 patients) nMTLE; and left (15/65 patients) pMTLE) using shape analysis (SA). There were significant differences among pMTLE versus nMTLE for age at seizure onset (20.2 ± 12.8 vs. 31.8 ± 16.7 years; p = .0029), duration of epilepsy (14.6 ± 12.7 vs. 21.3 ± 9.6 years; p = .0227), risk of refractoriness (p = .0067), frequency of antecedent febrile convulsions (FCs) (p < .001), as well as a history of epilepsy or FCs (p = .0104). All the subjects underwent the same 3-Tesla MRI protocol. Shape analysis of hippocampal formation was conducted comparing each group versus 44 matched controls.In all four subgroups, SA detected a significant atrophy in the corresponding hippocampus that coincided with the epileptogenic area. The damage was significantly more severe in patients with pMTLE (F value: 5.00) than in subgroups with nMTLE (F value: 3.50) and mainly corresponded to the CA1 subregion and subiculum. In the patients with MTLE, SA detects hippocampal damage that lateralizes with the epileptogenic area. Such damage is most prominent in the CA1 subregion and subiculum that are crucial in the pathogenesis of MTLE.     

Excitatory amino acid binding sites in the hippocampal region of Alzheimer''s disease and other dementias.

Quantitative receptor autoradiography was used to measure muscarinic cholinergic, benzodiazepine, kainate, phencyclidine (PCP), N-methyl-D-aspartate (NMDA) (measured in Tris acetate), quisqualate-sensitive, non-quisqualate-sensitive and total glutamate (measured in Tris chloride buffer) binding sites in adjacent sections of the hippocampal region of 10 Alzheimer's disease, nine control, and six demented, non-Alzheimer's disease postmortem human brains. The measurements were compared to the number of neurofibrillary tangles as revealed by Congo red staining of adjacent sections. All assays and measurements were done by observers blinded to the clinical diagnoses. Binding was decreased significantly for all ligands except quisqualate in stratum pyramidale of CA1 of the Alzheimer's disease brains. The binding loss was significantly greater for the non-quisqualate and NMDA sites than for the muscarinic, benzodiazepine and kainate sites with the total glutamate and PCP site losses being intermediate. Only the loss of benzodiazepine binding was significantly correlated with the number of neurofibrillary tangles. Lesser binding losses were seen in adjacent areas. This difference in the degree of binding decrease is consistent with the hypothesis that NMDA receptors are located on more distal dendrites of hippocampal neurons. There they may be relatively more vulnerable than the other receptors to the pathological process.     

Amygdalar and hippocampal MRI volumetric reductions in Parkinson's disease with dementia.

Parkinson's disease (PD) involves neuropathological changes in the limbic system that lead to neuronal loss and volumetric reductions of several nuclei. We investigated possible volumetric reductions of the amygdala and hippocampus associated to PD. We carried out magnetic resonance imaging (MRI) volumetric studies in 16 patients with PD and dementia (PDD), 16 patients with PD without dementia (PD), and 16 healthy subjects. The general analysis of variance (ANOVA) showed a significant group effect (for the amygdala, P = 0.01; for the hippocampus, P = 0.005). A post-hoc test demonstrated that the differences were due to PDD and control group comparisons for the amygdala (P = 0.008) and for the hippocampus (P = 0.004). In nondemented PD subjects, we observed an 11% reduction in the amygdala and a 10% reduction in the hippocampus compared with that in controls. In summary, demented PD patients have clear amygdalar and hippocampal atrophy that remains statistically significant after controlling for global cerebral atrophy. Nondemented PD patients also showed a degree of volumetric reduction in these structures although the differences were not statistically significant.     

Inflammation and atrophy in multiple sclerosis: MRI associations with disease course

Brain atrophy may be a useful surrogate marker of axonal loss and disease progression in multiple sclerosis (MS). Several studies have suggested that inflammatory disease activity is a risk factor for atrophy in the early stages of the disease, but may become less important later in the disease course. We aimed to investigate the relationships between atrophy and active inflammation at different stages of the disease course using brain volume measurements from magnetic resonance imaging (MRI) in patients with both relapsing-remitting (RR) (n=95) and secondary progressive (SP) (n=76) MS. Conventional dual echo and three-dimensional magnetization-prepared rapid-acquisition gradient echo imaging were performed in all patients and in 31 healthy controls. Supratentorial and infratentorial brain, and lateral ventricular volumes were determined using modern design stereology.Patients with SP MS had smaller supratentorial (p=0.003) and infratentorial brain volumes (p=0.0003), and larger lateral ventricles (p=0.02) than patients with RR MS. RR MS patients with T(1)-enhancing lesions had smaller supratentorial (p=0.02) and infratentorial (p=0.002) brain volumes and larger ventricles (p=0.002) than those without enhancing lesions. SP MS patients with enhancing lesions also had significantly larger lateral ventricles (p=0.03). Categorical analysis showed that more RR MS patients with enhancing lesions had smaller supratentorial brain (p=0.005), or larger lateral ventricular (p=0.028) volumes, and more SP MS patients with enhancing lesions had increased lateral ventricle volumes (p=0.013), than patients without enhancements. The number of enhancing lesions was significantly correlated with lateral ventricular volumes in both RR MS (r=0.39, p=0.0001) and SP MS (r=0.46, p<0.0001). Our data shows that the presence of active inflammation on a single MRI in the course of RR and SP MS, is associated with a higher risk and higher level of brain atrophy. These findings emphasise the important long-term relationship between inflammation and atrophy in MS and provide additional support for the strategy of early anti-inflammatory treatment to protect tissue integrity.     

The role of MRI in the diagnosis of olivopontocerebellar atrophy

Under the term of olivopontocerebellar atrophy different nosological pictures are grouped, all characterized by showing clinical signs of deficiency of the structures of the pons and of the cerebellum.The diagnosis of olivopontocerebellar atrophy has been made, until now, by clinical criteria while typical anatomopathological changes are found at the autoptic studies.We describe three patients affected by olivopontocerebellar atrophy, of different types and at different stages of disease.In all cases MRI showed a similar and typical picture of atrophy of the olivary eminences of the medulla oblongata resulting in straightening of the angle usually present on the ventral frontier between pons and medulla oblongata. This diagnostic tool demonstrated thus to be of primary relevance yet in the early phases of the disease.

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Sommario Sotto il termine di atrofia olivo-pontocerebellare si raggruppano quadri nosografici di verosimile diversa origine, caratterizzati tutti dalla presenza di segni clinici deficitari pontini e cerebellari. La diagnosi è stata sino ad ora solo clinica con conferma autoptica del danno pontocerebellare. Sono descritti tre casi di atrofia olivo-pontocerebellare, appartenenti, a tre distinti sottogruppi ed in fasi diverse della malattia. In tutti e tre i casi la MRI ha evidenziato un quadro di atrofia pontina e cerebellare ed una riduzione dimensionale delle olive bulbari che risultava in un allargamento dell'angolo pontobulbare normalmente rilevabile sulla faccia anteriore del tronco in proiezione laterale. L'esame si conferma di importanza diagnostica essenziale nella malattia sin dalle sue fasi iniziali.

     

Relations between hypometabolism in the posterior association neocortex and hippocampal atrophy in Alzheimer's disease: a PET/MRI correlative study

OBJECTIVES: Hippocampal atrophy and hypometabolism in the posterior association neocortex are two well known features of Alzheimer's disease. A correlation between these two features was reported twice previously, suggesting intriguing relations. This question has been reassessed, this time controlling for severity of dementia as well as assessing each side of the brain separately and using a voxel based image analysis in addition to the previously employed regions of interest (ROIs). PATIENTS AND METHODS: Eleven patients were studied with probable Alzheimer's disease and mild to moderate dementia in whom both volume MRI and PET assessed cerebral glucose consumption (CMRGlc) were available. Hypothesis driven correlations between hippocampal width (an index of atrophy) and CMRGlc were performed for two posterior association regions, the superior temporal and the inferior parietal (angular gyrus) cortices, using ROIs set separately for each hemisphere. To confirm significant correlations from the ROIs approach, if any, and to assess their specificity for the posterior association neocortex, CMRGlc image voxel based analysis of correlations with hippocampal width was then carried out. RESULTS: There was a significant correlation, in the positive-neurobiologically expected-direction, between right hippocampal width and right angular gyrus metabolism (p< 0.01, Spearman), which remained significant with Kendall partial correlation controlling for dementia severity (estimated by mini mental state scores). Statistical non-parametric mapping (SnPM) confirmed this correlation (p< 0.025), and showed a single additional correlation in the right middle temporal gyrus (p< 0.005), which is also part of the posterior association cortex. CONCLUSION: The findings with both ROIs and voxel based mapping replicate earlier reports of a relation between hippocampal atrophy and ipsilateral association cortex hypometabolism in Alzheimer's disease, and for the first time document that this relation is both region specific and independent of the dementing process itself. Why the correlation was significant only for the right hemisphere is unclear but may be related to the limited sample. Hippocampal-neocortical disconnection due to early and severe medial temporal lobe pathology may at least partly explain the posterior association cortex hypometabolism found in Alzheimer's disease.