Objectively measured prolonged sleep is associated with plasma cytokines in older adults with mild cognitive impairment.

This study aimed to determine whether objective sleep time is associated with the concentrations of various plasma cytokines in older adults with mild cognitive impairment (MCI). In total, 118 adults with MCI (66 women; mean age: 75.7 years) participated in this prospective cohort study. All participants were required to wear a wristband sensor for 7.8 days, on average, every 3 months for 1 year and undergo measurement of 27 plasma cytokines using multiplex immunoassays. After adjusting for potential confounders, the associations of total sleep time with cytokine concentrations were assessed by multiple linear regression analysis. The total sleep time was significantly correlated with plasma interleukin (IL)-9 and macrophage inflammatory protein (MIP)-1ß levels (r = 0.239, p = 0.009, and r = 0.242, p = 0.008, respectively). Moreover, these associations remained significant after adjusting for covariates, including demographic characteristics, lifestyle-related diseases, and apolipoprotein E status (ß = 0.272, 95% confidence interval: 0.095-0.448, p = 0.003, and ß = 0.27, 95% confidence interval: 0.092-0.449, p = 0.003, respectively). Thus, this study is the first to demonstrate the association between objective prolonged sleep and higher plasma IL-9 and MIP-1ß levels in older adults with MCI.

Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD) is a debilitating dementia characterized by progressive memory loss and aggregation of amyloid-ß (Aß) protein into amyloid plaques in patient brains. Mutations in presenilin (PS) lead to abnormal generation of Aß, which is the major cause of familial AD (FAD), and apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) onset. However, whether dysfunction of PS is involved in the pathogenesis of SAD is largely unknown. We found that ApoE secretion was completely abolished in PS-deficient cells and markedly decreased by inhibition of γ-secretase activity. Blockade of γ-secretase activity by a γ-secretase inhibitor, DAPT, decreased ApoE secretion, suggesting an important role of γ-secretase activity in ApoE secretion. Reduced ApoE secretion is also observed in nicastrin-deficient cells with reduced γ-secretase activity. PS deficiency enhanced nuclear translocation of ApoE and binding of ApoE to importin α4, a nuclear transport receptor. Moreover, the expression of PS mutants in PS-deficient cells suppressed the restoration effects on ApoE secretion compared with the expression of wild-type PS. Plasma ApoE levels were lower in FAD patients carrying PS1 mutations compared with normal control subjects. Our findings suggest a novel role of PS contributing to the pathogenesis of SAD by regulating ApoE secretion.SIGNIFICANCE STATEMENT Familial AD (FAD) typically results from mutations in the genes encoding amyloid precursor protein, presenilin 1 (PS1), or PS2. Many PS mutants have been found to exert impaired γ-secretase activity and increased amyloid-ß 42 (Aß42)/Aß40 ratio, which induce early amyloid deposition and FAD. On the other hand, apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) and contributes to AD pathogenesis because it has reduced Aß clearance capability compared with ApoE3 and ApoE2. FAD and SAD have long been considered to be caused by these two independent mechanisms; however, for the first time, we demonstrated that PS is essential for ApoE secretion and PS mutants affected ApoE secretion in vitro and in human samples, suggesting a novel mechanism by which PS is also involved in SAD pathogenesis.

A Case of Miller Fisher Syndrome with Cerebellar Hypoperfusion.

We report a case of a 76-year-old man with Miller Fisher syndrome presenting with acute ophthalmoplegia and ataxia. Cerebrospinal fluid analysis showed normocytosis with an increased protein level. Serum anti-GQ1b IgG and anti-GT1a IgG antibodies were positive. Based on these results, the patient was diagnosed with Miller Fisher syndrome. He was treated with two courses of intravenous immunoglobulin, which improved his neurological symptoms. Brain perfusion single-photon emission computed tomography showed that cerebellar blood flow was decreased in the acute stage of the disease and improved after treatment. Although the prevailing view is that ataxia in Miller Fisher syndrome patients is of a peripheral origin, this case suggests that cerebellar hypoperfusion contributes to the development of ataxia in Miller Fisher syndrome.

Changes in objectively measured lifestyle factors during the COVID-19 pandemic in community-dwelling older adults.

BACKGROUND: In this manuscript, we investigate whether objectively measured lifestyle factors, including walking steps, sedentary time, amount of unforced physical activity, level of slight and energetic physical activity, conversation time, and sleep parameters, were altered before and during the COVID-19 pandemic among community-dwelling older adults. METHODS: Data were obtained from a prospective cohort study conducted from 2015 to 2019 and a subsequent dementia prevention study undertaken in September 2020. Community-dwelling adults aged ≥ 65 years wore wearable sensors before and during the pandemic. RESULTS: A total of 56 adults were enrolled in this study. The mean age was 74.2 ± 3.9 years, and 58.9% (n = 33) of the participants were female. Moderate and vigorous physical activity time significantly decreased, and sedentary time significantly increased during the pandemic. CONCLUSIONS: This is the first study to demonstrate differences in objectively assessed lifestyle factors before and during the COVID-19 pandemic among community-dwelling older adults. The findings show that the pandemic has adversely affected physical activity among older adults living on their own in Japan.

Cerebrospinal Fluid Interleukin-6 in Immune Checkpoint Inhibitor-Induced Autoimmune Meningoencephalitis.

Immune checkpoint inhibitors (ICIs) have proven clinical benefits in various advanced cancers. However, despite their significant therapeutic efficacy, ICIs induce immune-related adverse events. Among these events, autoimmune meningoencephalitis often has severe effects on patients' outcomes, but its specific clinical features are still unclear. Here, we report two cases of ICI-associated meningoencephalitis with elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF). A 47-year-old woman (Case 1) with renal cell carcinoma developed severe headache after a seventh nivolumab administration. A neurological examination revealed jolt accentuation signs and hyperreflexia in all extremities. CSF analysis revealed a high IL-6 value (6,620 pg/mL) with marked pleocytosis. A 70-year-old woman (Case 2) who received an initial administration of nivolumab plus ipilimumab for renal cell carcinoma developed alterations of consciousness. She presented with impaired consciousness, neck stiffness, and hyperreflexia in all extremities. CSF analysis demonstrated a high IL-6 value (49.3 pg/mL) with mild pleocytosis. Both patients were treated with steroid pulse therapy (methylprednisolone 1,000 mg/day, 3 days), followed by the administration of oral predonisolone. The symptoms and laboratory findings improved in both cases. CSF IL-6 values were proportional to the severity of meningoencephalitis and other clinical parameters. These findings may help elucidate the mechanisms of central nervous system complications that are caused by ICIs.

Association of serum thyroid hormone levels with positron emission tomography imaging in non-demented older adults.

BACKGROUND: Although increasing evidence indicates that even variations in normal range thyroid function are associated with Alzheimer's disease (AD), the association between serum thyroid hormone levels within the reference range and AD biomarkers remains unclear. This study examined whether variations in thyroid hormones within the reference range are associated with brain amyloid burden and cortical glucose metabolism in older adults without dementia. METHODS: One hundred and two non-demented older adults underwent 11 C-Pittsburgh Compound B positron emission tomography (PiB-PET), 18 F-fluorodeoxyglucose (FDG)-PET, and measurement of serum thyroid-stimulating hormone (TSH), free triiodothyronine (T3), and free thyroxine (T4) levels. The discrimination between PiB-negative and PiB-positive subgroup was made on the basis of a subject's cortical uptake value ratio greater than 1.4. The association of serum thyroid hormone levels with global PiB or FDG uptake, and PiB or FDG uptake in each region of interest, including frontal and temporoparietal lobes and posterior cingulate gyrus, was analysed using a multiple regression model with adjustment for covariates, including age, gender, years of education, apolipoprotein E4 status or PiB uptake value. RESULTS: In the PiB-positive subgroup, the serum TSH levels positively associated with the global FDG uptake (ß = 0.471, P = 0.003) and FDG uptake in the frontal and temporoparietal lobes (ß = 0.466, P = 0.003, ß = 0.394, P = 0.012, respectively); the serum-free T3 levels negatively associated with the FDG uptake in the temporoparietal lobe and posterior cingulate region (ß = -0.351, P = 0.033, ß = -0.544, P = 0.002, respectively). The PiB-negative subgroup showed no significant associations. The serum thyroid hormone levels did not correlate with the global PiB uptake and PiB uptake in each region. CONCLUSIONS: The variations in the thyroid hormones within the reference ranges are associated with glucose metabolism, particularly in the specific regions affected by the neuropathologic changes of AD, in non-demented older adults with brain amyloid burden.

"Recurrent multiple cerebral infarctions related to the progression of adenomyosis: a case report".

BACKGROUND: Benign gynecologic tumor, such as uterine adenomyosis, has been suggested to develop hypercoagulability. Although some cases of cerebral infarction associated with adenomyosis have been reported, the mechanism of hypercoagulation initiated by adenomyosis is still not clear, and the therapeutic strategy is uncertain. CASE PRESENTATION: A 44-year-old woman was presented to our department with headache, left hand weakness, and gait disturbance during her menstrual phase. She had a history of adenomyosis and infertility treatment for 18 years and heavy menstrual bleeding. Magnetic resonance imaging on admission showed multiple hyperintense lesions in cortical and subcortical areas in the cerebrum and cerebellum on diffusion-weighted imaging. Transesophageal echocardiography showed neither embolic sources nor existence of foramen ovale. Her laboratory data revealed anemia, a high D-dimer level, and elevated levels of a mucinous tumor marker. She had adenomyosis and no malignancy was detected. Anticoagulation therapy with intravenous heparin followed by rivaroxaban did not prevent recurrence of cerebral infarction. We discontinued rivaroxaban, and started warfarin therapy with pseudomenopause treatment, which prevented recurrence for 6 months. Five months after her last pseudomenopause treatment, multiple cerebral infarctions occurred. Total hysterectomy was performed, which prevented recurrence of the multiple cerebral infarctions for 2 years without anticoagulation therapy. CONCLUSIONS: Our findings reveal for the first time that anticoagulation therapy, including novel oral anticoagulants, had no preventive effect against cerebral infarctions associated with adenomyosis in a middle-aged woman. Although pseudomenopause treatment temporarily prevented recurrence, resection of the adenomyosis might be the most effective therapy in these cases.

Induction of Genes Expressed in Endothelial Cells of the Corpus Callosum in the Chronic Cerebral Hypoperfusion Rat Model.

BACKGROUND: Cerebrovascular white matter lesions (WMLs) are associated with cognitive impairment in patients with subcortical vascular dementia. We performed a comprehensive gene expression analysis to elucidate genes associated with WML development in a chronic cerebral hypoperfusion rat model. METHODS: Brains of rats with bilateral carotid ligation (2VO, n = 10) and sham-operated rats (n = 5-10/group) were removed on days 1, 7, or 28 after surgery. Total RNA isolated from the corpus callosum was evaluated by microarray analysis and quantitative reverse transcription-polymerase chain reaction. RESULTS: On days 7 and 28, WMLs exhibited histologic changes. On day 7, 16 genes were differentially expressed between groups. mRNA levels of Ptprb, Kcnj8, Crispld2, Bcl6b, and Gja5 were differentially expressed in 2VO rats on day 7, but then returned to normal, whereas mRNA levels of Vwf and Trappc6a were upregulated after day 7. Immunohistochemistry showed that GJA5 and vWF were detected in endothelial cells, KCNJ8 in endothelial cells and astrocytes, CRISPLD2 in neurons and astrocytes, and TRAPPC6A in neurons. CONCLUSION: Our findings indicate novel genes that may be associated with WML development in the chronic cerebral hypoperfusion rat model, and suggest an important role of neurovascular dysfunction in the pathophysiology.

Evaluation of regional cerebral blood flow in Alzheimer's disease patients with subclinical hypothyroidism.

BACKGROUND: This study examined regional cerebral blood flow (rCBF) in Alzheimer's disease (AD) patients with and without subclinical hypothyroidism (SCH). METHODS: Eleven AD patients with SCH and 141 AD patients without SCH underwent brain perfusion single photon emission computed tomography (SPECT). The SPECT data were analyzed by statistical parametric mapping (SPM8) and FineSRT. RESULTS: AD patients with SCH showed a significantly decreased rCBF mainly in the temporal lobe and thalamus, whereas those without SCH showed a significantly decreased rCBF in the parietotemporal lobe and cingulate gyrus as well as the frontal lobe. CONCLUSION: Our findings suggest that SCH may affect cerebral perfusion in regions associated with the memory function.

Tolerability and efficacy of the long-term administration of memantine hydrochloride (Memary®) in patients with moderate to severe Alzheimer's disease.

AIM: Memantine hydrochloride (Memary®), launched in June 2011 in Japan, is used in patients with moderate to severe Alzheimer's disease. We performed an integrated analysis of data obtained from different clinical studies of memantine hydrochloride conducted between 2002 and 2011 in Japan in order to examine the long-term tolerability and efficacy of this drug at a dose of 20 mg/day. METHODS: Using clinical studies of memantine hydrochloride performed in Japan between 2002 and 2011, the therapeutic safety and the time course of MMSE scores in 702 subjects who had received memantine hydrochloride were examined. RESULTS: The mean duration of memantine treatment was 798.1 days, with the longest duration of 3,373 days (approximately nine years and two months). The incidence of adverse events every 52 weeks of treatment ranged from 71.0% to 88.9%, and the incidence of adverse drug reactions ranged from 5.6% to 32.1%, with no associations between the incidence of adverse events and the treatment duration. There were no adverse drug reactions specific to the long-term administration of this drug. The occurrence of "adverse events" was the primary reason for drug discontinuation. During the long-term study observation period, there were many cases of adverse events and treatment discontinuation due to the background factors of the subjects, including adverse events associated with aging and progression of the underlying conditions. In addition, treatment discontinuation was also associated with admission to a nursing home or facility due to changes in home nursing care. The degree of MMSE score reduction over time was lower in the patients treated with memantine than the expected MMSE score reduction observed in the untreated patients. CONCLUSIONS: Based on these findings, there are no issues regarding the tolerability of memantine hydrochloride administered at a dose of 20 mg/day over the long term. Considering changes in the MMSE score, the results indicated that memantine hydrochloride may inhibit worsening of the cognitive function for long periods of time in patients with Alzheimer's disease.

Cognitive Impairment and Early-onset Cerebral Amyloid Angiopathy in a Middle-aged Man with a History of Childhood Traumatic Brain Injury.

We herein report the a 42-year-old man with early-onset cerebral amyloid angiopathy (CAA) and a history of traumatic brain injury and neurosurgery in childhood. Computed tomography revealed cognitive impairment and recurrent lobar intracerebral hemorrhaging. Magnetic resonance imaging indicated cerebral microbleeds, and Pittsburgh compound B positron emission tomography detected brain amyloid deposition, mainly in the region of trauma and occipital lobes. Interestingly, the patient had no genetic predispositions or relevant family history. This case suggests that a single traumatic brain injury or neurosurgery in childhood can cause early-onset CAA.

X-linked Myotubular Myopathy Manifesting Carrier with Central and Peripheral Nervous System Involvement.

X-linked myotubular myopathy (XLMTM) is a rare genetic disorder caused by X-linked mutations in the MTM1 gene. Although heterozygous females are typically asymptomatic, affected cases have recently been reported. We herein report a case of XLMTM manifesting carrier of the pathogenic c.206dupG mutation in MTM1 with uncommon extramuscular symptoms. She developed gaze nystagmus and cognitive impairment in addition to muscle weakness. Electrophysiological studies and brain magnetic resonance imaging indicated the involvement of the central and peripheral nervous systems. XLMTM manifesting carriers may have a wider spectrum of clinical phenotypes than currently assumed. Appropriate follow-up of extramuscular and conventional muscular manifestations is important in such cases.

Comparison of Brain Amyloid Deposition and Cortical Glucose Metabolism Between Clinic- and Community-Based Cohort.

BACKGROUND: The differences in positron emission tomography (PET) imaging among older adults with mild cognitive impairment (MCI), according to the recruitment source, remain unclear. OBJECTIVE: To investigate the differences in brain amyloid deposition and cortical glucose metabolism according to recruitment source among older adults with MCI. METHODS: Participants in the clinic-based MCI cohort, who were referred to Oita University Hospital for cognitive decline, consisted of 90 adults with MCI. The community-based MCI cohort, which participated in a prospective cohort study, consisted of 118 adults with MCI. Participants underwent cognitive function evaluation, 11C-Pittsburgh compound B (PiB)-PET, and 18F-fluorodeoxyglucose (FDG)-PET. The prevalence of amyloid positivity and mean PiB and FDG uptake values were compared between the cohorts. Moreover, a voxel-by-voxel group study was performed to determine the areas with significant differences between the clinic- and community-based MCI cohorts. RESULTS: The prevalence of amyloid positivity and mean PiB uptake value in the clinic-based MCI cohort were significantly higher than those in the community-based MCI cohort (p < 0.001 and p < 0.001, respectively). The mean FDG uptake value in the clinic-based MCI cohort was significantly lower than that in the community-based MCI cohort (p < 0.001). SPM 8 analysis showed significantly increased PiB uptake in the precuneus and parietotemporal lobe and significantly decreased FDG uptake in the posterior cingulate in the clinic-based MCI cohort compared to the community-based MCI cohort. CONCLUSION: The prevalence and severity of amyloid pathology in older adults with MCI varied depending on the recruitment source.

Cerebrospinal fluid B-cell activating factor levels as a novel biomarker in patients with neurosarcoidosis.

OBJECTIVES: Neurosarcoidosis (NS) is a severe complication of sarcoidosis. Patients with NS often have poor outcomes. To improve both the quality of life and prognosis in patients with NS, accurate and reliable methods for early diagnosis and determining the efficacy of treatment are needed. This study aims to investigate B-cell-activating factor of the tumor necrosis factor family (BAFF) in cerebrospinal fluid (CSF) and elucidate the relationship between CSF BAFF levels and various parameters of NS. METHODS: We studied 20 patients with NS and 14 control subjects. We measured CSF BAFF levels in all subjects and investigated the relationship with clinical findings, serum and CSF measures, and magnetic resonance imaging (MRI) findings. RESULTS: CSF BAFF levels were significantly increased in patients with NS compared with controls (median 0.089 vs 0.04 ng/mL, p = 0.0005). CSF BAFF values were correlated with CSF findings-cell count, protein, angiotensin-converting enzyme, lysozyme, soluble interleukin-2 receptor, and immunoglobulin G-but not with serum parameters. CSF BAFF levels were especially higher in patients with abnormal intraparenchymal lesions of the brain and abnormal spinal MRI findings. CSF BAFF levels decreased significantly after immunosuppressive therapy. CONCLUSION: CSF BAFF may aid the quantitative evaluation of NS and may serve as a biomarker for this disease.

Lifestyle factors that affect cognitive function-a longitudinal objective analysis.

Background: Identifying lifestyle factors associated with cognitive decline has critical clinical and public health implications for dementia prevention in later life. The longitudinal associations of sleep and physical activity with cognitive function remain unclear. This study examined whether objectively measured sleep and physical activity were longitudinally associated with cognitive function in older adults over a three-year period. Methods: This prospective cohort study enrolled 855 community-dwelling adults aged 65 and older, who were followed from 2015 to 2019. All participants were required to wear a wearable sensor for 7 consecutive days every 3 months and had annual cognitive assessments. Wearable sensor data (August 2015-September 2019) and Mini-Mental State Examination (MMSE) scores (August 2015-April 2019) were collected over 3 years of follow-up. First, principal component analysis was conducted to reduce the dimensions of the sleep and physical activity variables to two principal components for inclusion in a mixed-effects model. The sleep index consisted of sleep efficiency, time awake after sleep onset, and waking frequency. The physical activity index was composed of walking comprised steps per day and time devoted to light or moderate-to-vigorous physical activity. A higher sleep index indicated poor sleep quality, whereas a lower physical activity index indicated less physical activity. Second, a linear mixed effect model was used to examine the longitudinal association of sleep and physical activity indices with cognitive decline over time. Results: In total, 855 adults were recruited for this study at baseline. Of these, 729 adults (85.3%) completed a measurement of lifestyle factors and an annual cognitive testing, whereas 126 were excluded because of death or loss during follow-up. After adjusting for age, sex, education level, and time, the sleep index was inversely associated with MMSE scores (estimate, -0.06229; standard error, 0.02202; p = 0.0047) and the physical activity index was positively associated with MMSE scores (estimate, 0.06699; standard error, 0.03343; p = 0.0453). Conclusion: Poor sleep quality and lower physical activity were significant risk factors for subsequent cognitive decline in older adults. The present study facilitates the development of novel evidence-based interventions for physical activity and sleep quality to delay cognitive decline.

Objective sleep was longitudinally associated with brain amyloid burden in mild cognitive impairment.

OBJECTIVE: Understanding the longitudinal association of objective sleep and physical activity with brain amyloid burden and cortical glucose metabolism has critical clinical and public health implications for dementia prevention in later life. METHODS: We enrolled 118 individuals aged ≥65 years with mild cognitive impairment, who were followed up on from August 2015 to September 2019. All participants continuously wore an accelerometer sensor for 7 consecutive days every 3 months and received annual 11 C-Pittsburgh compound-B and 18 F-fluorodeoxyglucose positron emission tomography (PET). Sleep and physical activity parameters were assessed using accelerometer sensor data and PET imaging was quantified using a standardized uptake-value ratio. Fifty-seven participants (48.3%) completed a lifestyle factor assessment and PET imaging over the 3-year period. A linear mixed-effects model was applied to examine the longitudinal association of sleep and physical activity parameters with PET imaging over the 3-year period, controlling for potential confounders. RESULTS: Sleep efficiency was inversely associated with amyloid uptake in the frontal lobe. Although sleep duration was positively associated with global amyloid uptake, particularly in the frontal lobe, their impact was extremely small. However, physical activity parameters were not significantly associated with the 11 C-Pittsburgh compound-B-uptake. Furthermore, sleep and physical activity parameters were not significantly associated with cortical glucose metabolism. INTERPRETATION: Lower sleep efficiency could be an early symptom of greater brain amyloid burden at the mild cognitive impairment stage. Therefore, the assessment of sleep may be useful for identifying individuals at higher risk for brain amyloid burden. Future longer term observational studies are required to confirm these findings.

Predicting positron emission tomography brain amyloid positivity using interpretable machine learning models with wearable sensor data and lifestyle factors.

BACKGROUND: Developing a screening method for identifying individuals at higher risk of elevated brain amyloid burden is important to reduce costs and burden to patients in clinical trials on Alzheimer's disease or the clinical setting. We developed machine learning models using objectively measured lifestyle factors to predict elevated brain amyloid burden on positron emission tomography. METHODS: Our prospective cohort study of non-demented, community-dwelling older adults aged ≥ 65 years was conducted from August 2015 to September 2019 in Usuki, Oita Prefecture, Japan. One hundred and twenty-two individuals with mild cognitive impairment or subjective memory complaints (54 men and 68 women, median age: 75.50 years) wore wearable sensors and completed self-reported questionnaires, cognitive test, and positron emission tomography imaging at baseline. Moreover, 99 individuals in the second year and 61 individuals in the third year were followed up. In total, 282 eligible records with valid wearable sensors, cognitive test results, and amyloid imaging and data on demographic characteristics, living environments, and health behaviors were used in the machine learning models. Amyloid positivity was defined as a standardized uptake value ratio of ≥ 1.4. Models were constructed using kernel support vector machine, Elastic Net, and logistic regression for predicting amyloid positivity. The mean score among 10 times fivefold cross-validation repeats was utilized for evaluation. RESULTS: In Elastic Net, the mean area under the receiver operating characteristic curve of the model using objectively measured lifestyle factors alone was 0.70, whereas that of the models using wearable sensors in combination with demographic characteristics and health and life environment questionnaires was 0.79. Moreover, 22 variables were common to all machine learning models. CONCLUSION: Our machine learning models are useful for predicting elevated brain amyloid burden using readily-available and noninvasive variables without the need to visit a hospital. TRIAL REGISTRATION: This prospective study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of Oita University Hospital (UMIN000017442). A written informed consent was obtained from all participants. This research was performed based on the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.

Effect of white matter lesions on brain perfusion in Alzheimer's disease.

BACKGROUND: This study examined the effect of white matter lesions (WMLs) on regional cerebral blood flow (rCBF) in patients with Alzheimer's disease (AD). METHODS: Ninety-eight patients with AD were included in the study (40 men and 58 women; mean age, 78.1 years). Cognitive function was assessed using the Mini-Mental State Examination. Brain magnetic resonance imaging (MRI) and (99m)Tc ethyl cysteinate dimer single photon emission computed tomography were performed in all subjects. AD patients were divided into two subgroups according to the presence of WMLs on MRI. A voxel-by-voxel group analysis using Statistical Parametric Mapping 8 was used to detect the differences in rCBF between the two groups. RESULTS: Fifty-seven of 98 AD patients (58%) showed mild to moderate WMLs on MRI. The prevalence of hypertension was significantly higher in AD patients with WMLs than in those without WMLs. AD patients with WMLs exhibited a significantly decreased rCBF in the anterior cingulate gyrus and insula, compared to AD patients without WMLs. CONCLUSION: We suggest that WMLs might influence brain regions associated with the limbic system in patients with AD.

Brain perfusion differences in parkinsonian disorders.

We aimed to objectively examine the brain perfusion differences between PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy. (99m) Tc ethylcysteinate dimer single-photon emission CT (SPECT) was performed in 28 patients with PD, 12 with Parkinson variant of multiple system atrophy, 19 with progressive supranuclear palsy, and 17 age- and sex-matched control subjects. A voxel-by-voxel group analysis, using statistical parametric mapping 8, was performed to detect the differences of regional cerebral blood flow among three diseases and control groups. Regional cerebral blood flow was measured using the noninvasive Patlak plot method and calculated using a fully automated region of interest technique. Progressive supranuclear palsy showed decreased regional cerebral blood flow in the cingulate gyrus and thalamus, whereas Parkinson variant of multiple system atrophy showed decreased regional cerebral blood flow in the cerebellum, compared with other patients and controls. Regional cerebral blood flow in the thalamus could be used to discriminate progressive supranuclear palsy from other diseases and control subjects with high sensitivity. These findings suggest that parkinsonian disorders, such as PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy show a distinct SPECT pattern in the frontal cortex, thalamus, and cerebellum. Moreover, the measurements of regional cerebral blood flow in the thalamus and cerebellum may be helpful in screening for the differential diagnosis of parkinsonian syndrome.

Relationship between thyroid hormone levels and regional cerebral blood flow in Alzheimer disease.

Subclinical thyroid disease and even variations in thyroid function within the normal range is associated with cognitive function and a risk of Alzheimer disease (AD). Several studies reported the effect of thyroid hormones on cerebral blood flow. The aim of this study was to objectively evaluate regional cerebral blood flow (rCBF) in association with thyroid hormone levels within the normal range in patients with AD. Serum thyroid-stimulating hormone (TSH), free T3, and free T4 levels were measured in 62 patients with AD (23 men and 39 women; age 56 to 91 y; mean age 77.3 y) and 27 control subjects (9 men and 18 women; age 61 to 93 y; mean age 75.8 y). The 99mTc ethylcysteinate dimer single photon emission computed tomography was performed in all subjects. The rCBF in the region of interest was measured by the noninvasive Patlak plot method and calculated using FineSRT, which is a fully automated region of interest technique. No significant correlation was found between thyroid hormone levels and Mini-Mental State Examination scores or global CBF values. Serum levels of TSH, but not free T3 or free T4, were significantly inversely correlated with rCBF in the middle and inferior temporal regions of right cerebral hemisphere in patients with AD. Control subjects showed no significant correlation between thyroid hormone levels and rCBF. Although these findings of a regional relationship must be considers preliminary, this study proposed the hypothesis that altered TSH levels within the normal range may be related to brain perfusion in right temporal region.