Satoshi Tanimukai

Medial temporal and whole-brain atrophy in dementia with Lewy bodies A volumetric MRI study

Objective: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. A recent pathologic study has indicated that the medial temporal lobe in patients with DLB was less atrophic than that in patients with AD. The purpose of this study was to examine whether medial temporal MRI volumetry was useful to differentiate DLB from AD clinically. Methods: We compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in 27 patients with probable DLB (based on the criteria of the Consortium on DLB International Workshop), 27 patients with probable AD(based on criteria of the National Institute of Neurological Disease and Stroke/Alzheimers Disease and Related Disorders Association), and 27 normal elderly subjects using an MRI-based volumetric technique. The three groups were matched for age and sex. Severity of cognitive disturbances represented by their Mini-Mental State Examination score was comparable between the DLB and AD groups. Results: Hippocampal volume (normalized to intracranial volume) in the DLB group was significantly larger than that in the AD group, but significantly smaller than that in the normal control group. There were no significant differences in the amygdala and whole-brain volume between the DLB group and the AD group, but the atrophies of the amygdala and whole brain were more severe in the DLB group than those in the control group. Conclusions: These findings indicate the usefulness of MRI hippocampal volumetry in clinically discriminating patients with DLB from patients with AD.

Apolipoprotein E ε4 and the pattern of regional brain atrophy in Alzheimer's disease

Background: Although the APOE ε4 allele increases the risk of developing AD, the effects of the ε4 allele on brain atrophy in clinical AD patients are controversial. Objective: To investigate a possible relationship between the genetic variants of APOE and brain atrophy in patients with AD. Methods: Using MRI-based volumetry techniques, the authors compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in probable AD patients (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association) with different APOE alleles. One group (n = 46) had the ε3/3 allele, one group (n = 46) had the ε3/4 allele, and one group (n = 46) had the ε4/4 allele. The three groups were matched for age, sex, disease duration, education level, and severity of dementia represented by their score of the Mini-Mental State Examination. A possible difference in pattern of cognitive deficits with dose of the APOE ε4 allele was also examined. Results: The normalized hippocampal volume was correlated with the number of APOE ε4 alleles (r = −0.285, p = 0.0007). The amygdalar volume was also correlated with the number of APOE ε4 alleles (r = −0.178, p = 0.037). The number of APOE ε4 alleles was positively correlated with the whole-brain volume (r = 0.185, p = 0.030). It was also correlated with Wechsler Adult Intelligence Scale–Revised performance IQ (r = 0.203, p = 0.017) and with Wechsler Memory Scale–Revised attention/concentration score (r = 0.191, p = 0.025). Conclusions: Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE ε4 allele on the brains of AD patients may have regional specificity.

Visual hallucinations and regional cerebral metabolism in dementia with lewy bodies (DLB)

To investigate the neurobiological bases of visual hallucinations in dementia with Lewy bodies (DLB), regional cerebral glucose metabolism was compared among three patient groups; DLB with visual hallucinations, DLB without visual hallucinations and Alzheimers disease (AD) without visual hallucinations. The regional metabolism was significantly lower in both DLB groups than in the AD group in the primary visual area and the posterior temporal, parietal and lateral occipital association areas. The hypometabolism in the right posterior temporal and parietal areas was significantly milder in DLB with visual hallucinations than in DLB without hallucinations. The hypometabolism in the primary visual cortex and the relatively preserved metabolism in the right temporoparietal association cortices may be associated with the occurrence of visual hallucinations in DLB patients.

Prevalence and Causes of Early-Onset Dementia in Japan A Population-Based Study

Background and Purpose— Few studies are available that have addressed the prevalence of early-onset dementia (EOD), including early-onset Alzheimer disease and other forms of dementia in Japan. Methods— A 2-step postal survey was sent to all of the 2475 institutions providing medical or care services for individuals with dementia in Japans Ibaraki prefecture (population, 2 966 000) requesting information on EOD cases. Data were then reviewed and collated. Results— We identified 617 subjects with EOD. The estimated prevalence of EOD in the target population was 42.3 per 100 000 (95% CI, 39.4 to 45.4). Of the illnesses that cause EOD, vascular dementia was the most frequent (42.5%) followed by Alzheimer disease (25.6%), head trauma (7.1%), dementia with Lewy bodies/Parkinson disease with dementia (6.2%), frontotemporal lobar degeneration (2.6%), and other causes (16.0%). Conclusions— The prevalence of EOD in Japan appeared to be similar to that in Western countries with the notable exception that vascular dementia was the most frequent cause of EOD in Japan.

Occipital Glucose Metabolism in Dementia with Lewy Bodies with and without Parkinsonism: A Study Using Positron Emission Tomography

Reduction of glucose metabolism in the occipital lobe is reported in dementia with Lewy bodies (DLB) and Parkinson’s disease. If dysfunction of the nigrostriatal system is responsible for occipital hypometabolism, (1) DLB patients with parkinsonism would show a lower occipital metabolism than do patients without parkinsonism, and (2) DLB patients without parkinsonism would show an occipital metabolism comparable to those of normal subjects and patients with Alzheimer’s disease (AD). To examine these hypotheses, we studied the regional cerebral metabolic rate of glucose (rCMRglc) in patients with a clinical diagnosis of DLB or AD, using 18F-fluorodeoxyglucose and positron emission tomography. The subjects consisted of 15 DLB patients with parkinsonism, 7 DLB patients without parkinsonism and 7 AD patients without parkinsonism. The medial and lateral occipital rCMRglc was significantly lower in the DLB patients without parkinsonism than in the AD patients. There were no significant differences in occipital metabolic rates between the DLB groups with and without parkinsonism. DLB patients without parkinsonism showed a significant reduction of occipital glucose metabolism which is comparable with that of DLB patients with parkinsonism. The neurobiological bases of occipital hypometabolism in DLB may be pathological processes in the brainstem or basal forebrain structures other than the nigrostriatal system.

Neuronal substrates for semantic memory: A positron emission tomography study in Alzheimer's disease

We examined 57 patients with mild Alzheimer’s disease by using three kinds of verbal semantic memory tests (category fluency, confrontation naming and generation of verbal definition) and correlated each score with regional cerebral glucose metabolism determined by 18F-fluorodeoxyglucose and positron emission tomography. The scores of all three verbal semantic memory tests correlated significantly with regional cerebral glucose metabolism in the left inferior temporal gyrus, even after controlling for the effects of age, sex and educational attainment. In contrast, the scores of the word recall test did not correlate significantly with regional cerebral glucose metaboliosm in the left inferior temporal gyrus, neither before nor after controlling for these confounders. Our results suggested that the left inferior temporal lobe contributes to verbal semantic memory.

Effect of the Apolipoprotein E ε4 Allele on White Matter Hyperintensities in Dementia

Background and Purpose—The clinical significance of the apoE e4 allele in white matter changes in patients with dementia has been a subject of debate. We studied the association between the apoE e4 allele and white matter hyperintensities (WMHs) before and after control for (1) potential vascular risk factors and (2) the presence of lacunar infarcts in patients with dementia. Methods—The subjects were 131 patients with dementia who had either Alzheimer’s disease or vascular dementia, or a combination of these 2 types of dementia, with or without WMHs, lacunar infarcts, or both. The association of the e4 allele with WMHs was examined before and after control for age, sex, duration of symptoms, education level, severity of dementia, presence of lacunar infarcts, and potential vascular risk factors, including hypertension, diabetes mellitus, lipid disorders, smoking habit, drinking habit, and cardiac diseases. Results—WMHs were observed in 73 (55.7%) of the patients. Neither the number of apoE e4 alleles nor...

Neuropathologic changes in the gerbil brain after chronic hypoperfusion.

Background and Purpose An animal model has been developed to elucidate the pathological changes in brain cytoskeletal proteins during chronic hypoperfusion. Methods Newly designed coiled clips were placed around both carotid arteries of Mongolian gerbils (n=10) to cause stenosis without occlusion. Those gerbils showing impaired learning ability by the passive avoidance paradigm were killed for neuropathologic study after 12 weeks. Results The brains showed ventricular dilatation, cortical atrophy, and rarefaction of the white matter. Immunoreactivity to anti-microtubule-associated protein 2 antibody in the cerebral cortex and the hippocampus was diminished, indicating dendritic changes of neurons. In the thalamic axonal regions, staining with anti-neurofilament 200K protein antibody was increased, suggesting increased amounts of neurofilament proteins or increased phosphorylation of the protein. Increased immunoreactivity to anti-glial fibrillary acidic protein antibody was observed in a wedge-shaped configuration, corresponding to the border zone of perfusion by small vessels. Conclusions These findings suggest that changes in the cytoskeletal proteins in dendrites, axons, and glial cells may cause neuronal death under conditions of chronic cerebral hypoperfusion. (Stroke 1993;24:259–265)

Fall-related injuries in dementia with Lewy bodies (DLB) and Alzheimer's disease

Repeated falls are reported as one of the clinical characteristics in dementia with Lewy bodies (DLB). We examined the incidence of fall‐related injuries in 561 dementia patients with various clinical diagnoses, including DLB and Alzheimer’s disease (AD), in a ward established for dementia research. The incidence of fall‐related injuries was significantly higher in DLB patients (10.7%) than in AD patients (1.1%) (P < 0.001). The high incidence in those patients with DLB cannot be attributed to Parkinsonism because none of the DLB patients with injuries showed extrapyramidal sign. Our observations suggest that patients with a clinical diagnosis of DLB have a high risk of fall‐related injuries, even though they do not show Parkinsonism. An appropriate clinical discrimination between DLB and AD is recommended to manage and prevent fall‐related injuries.

Apathy correlates with prefrontal amyloid β deposition in Alzheimer's disease

Objective Neuropsychiatric symptoms affect many patients with Alzheimers disease (AD). (11C)Pittsburgh Compound-B (PIB) positron emission tomography (PET) has enabled the in vivo visualisation of brain amyloid-β (Aβ) deposition. This study exploratively investigated the correlation between brain Aβ deposition measured by (11C)PIB PET and neuropsychiatric symptoms in AD. Methods Participants were 28 patients (15 women, 13 men) with PIB-positive AD. Clinical assessments included Mini-Mental State Examination, Clinical Dementia Rating scale, neuropsychiatry inventory (NPI) and frontal assessment battery. All patients underwent three-dimensional T1-weighted MRI and (11C)PIB PET. The distribution volume ratio (DVR), an index of (11C)PIB retention and, thus, Aβ deposition, was estimated voxel by voxel from (11C)PIB PET data with partial volume correction. Voxel-based correlation analysis was performed to assess the relationships between DVR and each NPI subscale. Additionally, voxel-based analysis of covariance (ANCOVA) of the DVR images was performed between Patients with AD with and without each neuropsychiatric symptom. Voxel-based morphometry analysis of MRI was also performed. Results Apathy subscale was correlated with (11C)PIB retention in the bilateral frontal and right anterior cingulate. (11C)PIB retention was greater in the bilateral frontal cortex of patients with AD with apathy than those of without apathy. Overlapping areas between the two analyses were the bilateral orbitofrontal gyrus and left superior frontal gyrus. Other NPI subscales were not correlated with (11C)PIB retention. Voxel-based morphometry analysis of MRI showed no significant cluster of correlation between grey matter volume and NPI subscales. Conclusions This study revealed that prefrontal Aβ deposition correlates with apathy.