Association of Intrinsic Functional Connectivity between the Locus Coeruleus and Salience Network with Attentional Ability.

The locus coeruleus (LC) is a brainstem region associated with broad neural arousal because of norepinephrine production, but it has increasingly been associated with specific cognitive processes. These include sustained attention, with deficits associated with various neuropsychological disorders. Neural models of attention deficits have focused on interrupted dynamics between the salience network (SAL) with the frontoparietal network, which has been associated with task-switching and processing of external stimuli, respectively. Conflicting findings for these regions suggest the possibility of upstream signaling leading to attention dysfunction, and recent research suggests LC involvement. In this study, resting-state functional connectivity and behavioral performance on an attention task was examined within 584 individuals. Analysis revealed significant clusters connected to LC activity in the SAL. Given previous findings that attention deficits may be caused by SAL network switching dysfunctions, findings here further suggest that dysfunction in LC-SAL connectivity may impair attention.

Untreated hypertension and prognosis paradox in acute ischemic stroke.

INTRODUCTION: This study is to explore the long-term functional outcome of antihypertensive medication-naïve, untreated hypertension (HTN) patients with acute ischemic stroke compared to those with no prior HTN and those with treated HTN. PATIENTS AND METHODS: We analyzed a prospectively collected stroke registry of all patients with acute ischemic stroke consecutively admitted to Incheon St. Mary's Hospital. Patients who received reperfusion therapy were excluded. Long-term functional outcomes were assessed at a 3-month follow-up visit using the modified Rankin Scale. RESULTS: A total of 1044 patients was enrolled. Compared to patients with no or treated HTN, those with untreated HTN had higher odds for more favorable outcomes (adjusted odds ratio (OR): 1.7 [95% CI: 1.0-2.7, p = 0.050*] and 1.7 [95% CI: 1.0-2.8, p = 0.047*], respectively) when the stroke was large vessel atherosclerosis (LAA)/cardioembolic (CE) with large vessel occlusion/stenosis. However, no such association was observed when there was no large vessel occlusion or stenosis, in total patients, or if the index stroke was related to SVO. In untreated HTN patients with LAA/CE and large vessel occlusion/stenosis compared to patients in the lowest mean arterial pressure quartile (< 96.7 mmHg), patients in the second and third highest quartiles had higher odds of favorable outcomes. CONCLUSIONS: Patients with untreated HTN had significantly more favorable outcomes at 3 months after ischemic stroke compared to those with no or treated HTN when the stroke was LAA/CE with large vessel occlusion/stenosis. Untreated HTN patients also showed an association between higher MAP and favorable outcomes.

Multiple chronic lacunes predicting early neurological deterioration and long-term functional outcomes according to TOAST classification in acute ischemic stroke.

INTRODUCTION: Studies regarding multiple chronic lacunes (MCLs) and clinical outcome according to stroke etiology are scarce. We sought to evaluate the association between MCL and short-term/long-term clinical outcomes according to stroke etiology. PATIENTS AND METHODS: We analyzed a prospectively collected stroke registry of acute ischemic stroke patients over 4 years. The enrolled patients were classified as having large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolic (CE) stroke, and other etiology. The early neurological deterioration (END) and favorable outcome at 3 months were assessed. RESULTS: A total of 1070 patients were enrolled. Patients with MCL had significantly more END compared to those without MCL both in total population (adjusted odds ratio (OR), 1.7; 95% confidence interval [CI], 1.1-2.5; p = 0.013*) and in the LAA group (adjusted OR, 2.3; 95% CI, 1.3-4.2, p < 0.006). Patients with MCL had a significantly lower OR for favorable outcome at 3 months compared to those without MCL both in total population (adjusted OR, 0.7; 95% CI, 0.5-1.0, p = 0.035) and in the LAA group (adjusted OR, 0.6; 95% CI, 0.3-1.0, p = 0.043). However, MCL was not associated with END or long-term functional outcome in patients with SVO, CE, or other etiology. CONCLUSIONS: The presence of MCL was an independent predictive factor for END as well as long-term poor functional outcome in acute ischemic stroke patients. These associations were only observed in patients with LAA, not in those with SVO, CE, or other etiology.

Changes of regional cerebral blood flow after repeated transcranial direct current stimulation in healthy participants: a pilot study.

BACKGROUND: Transcranial direct current stimulation (tDCS) can potentially enhance brain function and cognition in healthy individuals as well as in patients with cognitive impairment. However, neural correlates of repeated tDCS remain relatively unexplored in a healthy population. PURPOSE: To assess the effects of repeated tDCS on regional cerebral blood flow (rCBF) in healthy volunteers in a pilot investigation. MATERIAL AND METHODS: Five healthy adults received bifrontal tDCS to the dorsolateral prefrontal cortex (F3-F4 montage, 1 mA intensity, 30 minutes/session, five sessions/week) over four weeks. All participants underwent brain single-photon emission computed tomography (SPECT) scans at baseline and one week after the last tDCS session. Changes in rCBF were examined using Statistical Parametric Mapping. RESULTS: Resting rCBF was significantly improved in the right superior frontal gyrus at the follow-up (P < 0.001). Adverse events were not reported and the stimulation was well-tolerated. CONCLUSION: Repeated tDCS may be effective for enhancing brain function in healthy participants. Larger sham-controlled studies should be performed to confirm our preliminary findings.

The Prevalence of Microembolic Signals in Transcranial Doppler Sonography With Bubble Test in Acute Ischemic Stroke.

OBJECTIVES: Transcranial Doppler ultrasound (TCD) is noninvasive and highly sensitive and specific for the diagnosis of patent foramen ovale (PFO). We evaluated the diagnostic implications of the TCD with a saline agitation test as a routine work-up for ischemic stroke patients. METHODS: A TCD bubble study was performed in all consecutive ischemic stroke patients as a routine work-up. We evaluated the prevalence of microembolic signals (MES) for each stroke etiology and the optimal number of MES for predicting the PFO-attributable stroke. RESULTS: Subjects (N = 499) with acute ischemic stroke were enrolled. A significant fraction of patients had MES during both normal respiration (5.7-44.4%) and the Valsalva maneuver (19.5-55.6%) across all stroke etiology categories. The optimal MES threshold for the diagnosis of PFO-attributable stroke confirmed by transesophageal echocardiography was 46 MES during the Valsalva maneuver (96% sensitivity and 95% specificity). Applying ≥46 MES during the Valsalva maneuver as a threshold effectively increased the ability to differentially diagnose PFO-attributable stroke from other etiologies. The number of MES during the Valsalva maneuver was negatively correlated with increasing age (r = -.108; P = .016). CONCLUSIONS: A significant fraction of patients had right to left shunt across all Trial of ORG 10172 in Acute Stroke Treatment etiologies. A threshold number of MES facilitated the differential diagnosis of PFO-attributable stroke from other etiologies, and the optimal threshold was 46 MES during the Valsalva maneuver.

Possible neuroprotective effects of rasagiline in Alzheimer's disease: a SPECT study.

BACKGROUND: The current lack of effective treatments for Alzheimer's disease (AD) and the rapidly increasing burden of the disease highlight the urgent need to find new treatments. Despite accumulating evidence of the beneficial effects of rasagiline in neurodegenerative diseases such as Parkinson's disease, the effects of rasagiline on the brains of patients with AD have not been elucidated. PURPOSE: To examine the effects of rasagiline on regional cerebral flow (rCBF) in patients with AD using single photon emission computed tomography (SPECT). MATERIAL AND METHODS: Among 22 patients with AD, 11 patients received adjunctive rasagiline at 1 mg/day in conjunction with acetylcholinesterase inhibitors (AChEI); 11 patients were only treated with AChEI for about 1.6 years. All patients underwent brain technetium-99m hexamethylpropylene amine oxime SPECT scans and clinical assessments at baseline and follow-up visits. Annual percent changes in rCBF were compared between the groups in a voxel-wise manner. RESULTS: SPECT analysis revealed that the rasagiline-treated group showed more increased rCBF in the cingulate gyrus, inferior frontal gyrus, putamen, and thalamus compared to the comparison group (P < 0.005). CONCLUSION: We demonstrated that adjunctive rasagiline treatment may have beneficial effects on brain perfusion in patients with AD, suggesting potential neuroprotective effects.

Electroencephalography in Predicting Short-Term Clinical Outcomes after Cardiac Arrest.

BACKGROUND: Early consciousness recovery after cardiac arrest (CA) is one of the most explicit and self-evident prognostic factors for clinical outcomes. We aimed to evaluate the prognostic value of electroencephalography (EEG) phenotypes according to the American Clinical Neurophysiology Society's Critical Care EEG classification for predicting early recovery after CA. METHODS: Consecutive patients admitted to the ICU after CA were enrolled. We analyzed Glasgow Coma Scale (GCS) score within 10 days after CA and evaluated mortality within 28 days according to EEG pattern subtype. RESULTS: Among the total of 71 patients, 9 had periodic discharges (PDs) EEG pattern, 4 had rhythmic delta activity (RDA), 8 had spike-and-wave (SW), 22 had low voltage, 5 had burst suppression, and 23 had other EEG patterns. Initial GCS scores, GCS scores 3 days after CA (or 3 days after targeted temperature management [TTM]), and 10 days after CA (or 10 days after TTM) were significantly different among EEG subtypes (p < 0.001, respectively) (Table 2). GCS scores were significantly higher in RDA and the other EEG group compared to the PDs, SW, low voltage, and burst suppression groups (p < 0.001). Significant group × time interactions were observed for the follow-up period between EEG phenotypes (p < 0.001) demonstrating the most increase in the other EEG pattern group. CONCLUSIONS: Consciousness states were significantly worse in the PDs, SW, burst suppression, and low-voltage groups compared to the RDA and the other EEG pattern within 10 days after CA. The degree of consciousness recovery differed significantly by EEG pattern subtype within 10 days.

Correction to: Cerebral perfusion abnormalities in patients with persistent postural-perceptual dizziness (PPPD): a SPECT study.

The authors inadvertently forgot to provide the following funding information in the original publication: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (2018R1A6A3A11041118).

Cerebral perfusion abnormalities in patients with persistent postural-perceptual dizziness (PPPD): a SPECT study.

Persistent postural-perceptual dizziness (PPPD) is a recently defined syndrome with chronic dizziness interrupting daily life. Although the high levels of anxiety and functional changes in postural control strategy and multi-sensory information processing and integration may be underlying the pathophysiology, its neural mechanisms are poorly understood. The aim of this study was to examine the regional cerebral blood flow (rCBF) in patients with PPPD using single photon emission computed tomography (SPECT). A total of 25 patients with PPPD and 25 healthy controls participated in the study. All participants underwent brain SPECT and the patients completed the Dizziness Handicap Inventory. SPECT images were compared between the groups, and the correlation of rCBF and disease severity/duration was assessed in patients. Compared with controls, PPPD patients showed a significantly decreased rCBF in the insula and frontal lobe, mainly in the left posterior insula, bilateral superior frontal gyrus, right inferior frontal gyrus, right precentral gyrus, and left medial orbital gyrus. Additionally, PPPD patients showed a significant rCBF increase in the bilateral cerebellum compared with controls. The results of our study suggest that the altered rCBF in the insular, frontal, and cerebellar cortices might be reflecting the process of maladaptation and the compensatory responses for the changes in PPPD.

Blood-brain barrier permeability assessed by perfusion computed tomography predicts hemorrhagic transformation in acute reperfusion therapy.

Hemorrhagic transformation (HT) is one of the most feared complications of acute recanalization therapies. The aim of this study was to evaluate whether blood-brain barrier permeability (BBBP) imaging can predict HT in the setting of acute recanalization therapy and to determine the sensitivity and specificity of BBBP for the prediction of HT according to the type of reperfusion therapy. We assessed a total of 46 patients who received recanalization therapy (intravenous (IV) recombinant tissue plasminogen activator (tPA), mechanical thrombectomy with a stent retriever or both) for acute ischemic stroke within the internal carotid artery or middle cerebral artery. BBBP above the threshold was significantly associated with HT after adjustment for confounding factors in all patients (OR 45.4, 95% CI 2.9~711.2, p = 0.007), patients who received IV tPA (OR 20.1, 95% CI 1.2-336.7, p = 0.037), and patients who received endovascular therapy (OR 47.2, 95% CI 1.9-1252.5, p = 0.022). The sensitivity and specificity of the initial BBBP measurement as a predictor of HT in the overall 46 patients were 80 and 71%, respectively. These values were 75 and 64% in only IV tPA group, 100 and 80% in only endovascular group, 77 and 67% in IV tPA with or without endovascular therapy group, and 86 and 76% in endovascular therapy with or without bridging IV tPA therapy group. Increased pretreatment BBBP values were significantly associated with HT after acute recanalization therapy. This correlation with HT was stronger in patients receiving endovascular mechanical thrombectomy than in patients receiving IV rtPA.

Prognostic Value of Serum D-Dimer in Noncardioembolic Ischemic Stroke.

BACKGROUND: Although D-dimer levels are significantly associated with cardioembolic infarction, the significance of D-dimer levels in relation to the severity and functional outcomes of other stroke subtypes, such as lacunar and large artery atherosclerosis infarction, remains unclear. The purpose of this study was to evaluate whether elevated initial D-dimer levels are significantly and cross-sectionally associated with poor functional outcomes at each time point during a 9-month follow-up period. We also investigated the significance of D-dimer levels in longitudinal temporal changes of functional outcomes in these patients. METHODS: We recruited 146 patients with lacunar infarction and 161 patients with large artery atherosclerosis infarction who were consecutively admitted to our hospital after acute stroke. Serum D-dimer levels were evaluated initially and the modified Rankin scale were measured initially and at 1-, 3-, 6-, and 9-month follow-up visits. RESULTS: Patients with higher D-dimer levels had significantly worse initial functional outcomes, and these worse outcomes were maintained throughout the 9-month follow-up period compared with the low D-dimer group. However, regardless of stroke subtype, D-dimer levels did not influence long-term changes in functional outcomes over the 9-month follow-up period. CONCLUSION: This study suggests that elevated D-dimer levels can be used as a surrogate marker for poor functional outcomes only during the acute stage. Further evaluation of serum D-dimer levels could provide a helpful predictive marker for stroke prognosis.

Parkinson's disease might increase the risk of cerebral ischemic lesions.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. Cerebrovascular diseases such as cerebral ischemic lesion (CIL) also commonly occur in elderly adults. However, previous studies on the relationship between PD and cerebrovascular disease have not found consistent results. Therefore, we conducted this study to evaluate whether or not PD is related to an increased prevalence of ischemic cerebrovascular lesions. METHODS: This study recruited 241 patients with PD and 112 healthy controls (HCs). All subjects underwent brain magnetic resonance imaging and general neuropsychological tests. The motor severity of PD was evaluated according to the Hoehn and Yahr stage (HY stage), and the severity of CIL in all subjects was classified according to Fazekas grade. The PD patients were classified into two subgroups according to HY stage (Group 1 - HY 1, 2; Group 2 - HY 3 to 5). RESULTS: Among all PD patients, 76% had small vessel disease, while 44% of all HCs had small vessel disease (p<0.001). Regarding the difference between the two subgroups according to motor severity, group 2 showed significantly higher Fazekas scale score and more severe CIL, indicating a higher prevalence of small vessel disease compared to group 1. CONCLUSION: This study demonstrates that PD patients have a significantly higher prevalence of CIL compared to HCs. Therefore, although the present study is not a large-scale study, we cautiously suggest that PD can play an important role as a risk factor in the occurrence of ischemic cerebrovascular disease.

Simultaneous acoustic stimulation of human primary and secondary somatosensory cortices using transcranial focused ultrasound.

BACKGROUND: Transcranial focused ultrasound (FUS) is gaining momentum as a novel non-invasive brain stimulation method, with promising potential for superior spatial resolution and depth penetration compared to transcranial magnetic stimulation or transcranial direct current stimulation. We examined the presence of tactile sensations elicited by FUS stimulation of two separate brain regions in humans-the primary (SI) and secondary (SII) somatosensory areas of the hand, as guided by individual-specific functional magnetic resonance imaging data. RESULTS: Under image-guidance, acoustic stimulations were delivered to the SI and SII areas either separately or simultaneously. The SII areas were divided into sub-regions that are activated by four types of external tactile sensations to the palmar side of the right hand-vibrotactile, pressure, warmth, and coolness. Across the stimulation conditions (SI only, SII only, SI and SII simultaneously), participants reported various types of tactile sensations that arose from the hand contralateral to the stimulation, such as the palm/back of the hand or as single/neighboring fingers. The type of tactile sensations did not match the sensations that are associated with specific sub-regions in the SII. The neuro-stimulatory effects of FUS were transient and reversible, and the procedure did not cause any adverse changes or discomforts in the subject's mental/physical status. CONCLUSIONS: The use of multiple FUS transducers allowed for simultaneous stimulation of the SI/SII in the same hemisphere and elicited various tactile sensations in the absence of any external sensory stimuli. Stimulation of the SII area alone could also induce perception of tactile sensations. The ability to stimulate multiple brain areas in a spatially restricted fashion can be used to study causal relationships between regional brain activities and their cognitive/behavioral outcomes.

Autonomic Nervous System Dysfunction in Patients With Parkinson Disease Having Depression.

BACKGROUND AND AIM: Both depression and cardiovascular autonomic dysfunctions, such as orthostatic hypotension, supine hypertension, and the absence of normal nocturnal blood pressure (BP) fall ("nondipping"), occur relatively commonly in Parkinson disease (PD); however, the relationship between depression and cardiovascular autonomic abnormalities has not been established. In this study, we sought to determine whether the cardiovascular autonomic abnormalities found in PD are associated with depression. METHODS: Among 129 nondemented, levodopa-naive patients with mild PD, 44 had depression. Orthostatic vital signs and ambulatory 24-hour BP monitoring were recorded, and geriatric depressive scales were obtained in all patients. Associations between orthostatic hypotension, supine hypertension, nocturnal hypertension, nondipping, and depression were analyzed. The ratio of the standard deviation of 24-hour heart rate to that of systolic BP (SBP) was utilized as an index of baroreflex-cardiovagal function. RESULTS: Depression was associated with orthostatic hypotension, and patients with depression had higher SBP change during orthostasis and attenuated cardiovagal dysfunction as observed during ambulatory BP monitoring. Across individuals, values for orthostatic changes in BP were correlated with values for geriatric depressive scale. CONCLUSION: Depression is associated with neurocirculatory abnormalities-especially orthostatic hypotension-in early PD. Although the association does not imply causation, this result suggests that depression in PD might be associated with functional impairment of the autonomic nervous system and its pathologic substrate.

Cardiovascular autonomic dysfunctions in elderly patients with essential tremor: comparison with healthy controls.

Questionnaire-based analyses show that patients with essential tremor (ET) may have several autonomic dysfunctions, especially in the cardiovascular and genitourinary domains; yet the laboratory correlates of autonomic dysfunction in ET are unknown and have not been studied. Herein, we explored whether sympathetic and parasympathetic functions differed between control subjects and patients with ET. Seventy-five elderly patients with ET were enrolled in this study, along with 25 age-matched controls. Orthostatic vital signs, ambulatory 24-h blood pressure monitoring and 24-h Holter monitoring values were recorded and metaiodobenzylguanidine (MIBG) uptake was assessed using the heart-to-mediastinum ratio (H/M ratio). The frequencies of orthostatic hypotension, supine hypertension, nocturnal hypertension and non-dipping were not different between the ET patients and the controls, although ET patients had more episodes of orthostatic intolerance. The ET group also had similar heart rate variations as the control group for all the time-domains. The mean H/M ratios for the ET group were not statistically different from that of the control group. This result proves that the autonomic control of the cardiovascular system is normal in ET.

Alteration patterns of brain glucose metabolism: comparisons of healthy controls, subjective memory impairment and mild cognitive impairment.

BACKGROUND: Some groups have focused on the detection and management of subjective memory impairment (SMI) as the stage that precedes mild cognitive impairment (MCI). However, there have been few clinical studies that have examined biomarkers of SMI to date. PURPOSE: To investigate the differences in glucose metabolism as a prodromal marker of dementia in patients with SMI, MCI, and healthy controls using brain F-18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET). MATERIAL AND METHODS: Sixty-eight consecutive patients with SMI, 47 patients with MCI, and 42 age-matched healthy subjects were recruited. All subjects underwent FDG-PET and detailed neuropsychological testing. FDG-PET images were analyzed using the statistical parametric mapping (SPM) program. RESULTS: FDG-PET analysis showed glucose hypometabolism in the periventricular regions of patients with SMI and in the parietal, precentral frontal, and periventricular regions of patients with MCI compared with healthy controls. Interestingly, hypometabolism on FDG-PET was noted in the parietal and precentral frontal regions in MCI patients compared to SMI patients. CONCLUSION: The results suggest that hypometabolism in the periventricular regions as seen on FDG-PET may play a role as a predictive biomarker of pre-dementia, and the extension of reduced glucose metabolism into parietal regions likely reflects progression of cognitive deterioration.

Comparison of I-123 MIBG planar imaging and SPECT for the detection of decreased heart uptake in Parkinson disease.

Decreased myocardial uptake of I-123 metaiodobenzylguanidine (MIBG) is an important finding for diagnosis of Parkinson's disease (PD). This study compared I-123 MIBG SPECT and planar imaging with regard to their diagnostic yield for PD. 52 clinically diagnosed PD patients who also had decreased striatal uptake on FP-CIT PET/CT were enrolled. 16 normal controls were also included. All underwent cardiac MIBG planar scintigraphy and SPECT separately. Myocardial I-123 MIBG uptake was interpreted on planar and SPECT/CT images separately by visual and quantitative analysis. The final diagnosis was made by consensus between two readers. Kappa analyses were performed to determine inter-observer agreement for both methods. Sensitivity, specificity, and accuracy were compared with McNemar's test. The sensitivity, specificity, and accuracy were 84.6, 100, and 88.2% for planar images and 96.2, 100 and 97.1% for SPECT, respectively, with a significant difference between the two imaging methods (p < 0.031). All inter-observer agreements were almost perfect (planar scintigraphy: κ = 0.82; SPECT: κ = 0.93). Heart-to-mediastinum ratios from PD patients with negative planar and positive SPECT scans (group A) and patients with positive planar and positive SPECT scans (group B) were 1.69 ± 0.16 (1.59-1.85) and 1.41 ± 0.15 (1.20-1.53), respectively, and showed significant difference (p = 0.023). Lung-to-mediastinum ratios for groups A and B were 2.16 ± 0.20 (1.96-2.37) and 1.6 ± 0.19 (1.3-1.78), respectively, and were significantly higher in the former (p = 0.001). I-123 MIBG SPECT has a significantly higher diagnostic performance for PD than planar images. Increased lung uptake may cause false-negative results on planar imaging.

Subtype of mild cognitive impairment in elderly patients with essential tremor.

BACKGROUND AND AIMS: Several studies have demonstrated that patients with essential tremor (ET) may also have mild cognitive impairments (MCIs), and cross-sectional and population-based studies have shown that ET is associated with prevalent dementia. Different presentations of MCI are suggested to be associated with different pathologies. For example, amnestic MCI may be associated with Alzheimer disease. Therefore, in this study, we explored whether the MCI subtype in patients with ET (MCI-ET+) is different from the MCI subtype in patients without ET attending a memory outpatient clinic (MCI-ET-). METHODS: Using a case-control study design, cognitive status in MCI patients with ET and without ET was assessed by neuropsychological testing. Patients with MCI were stratified into groups: amnestic and nonamnestic MCI, or single-domain and multidomain MCI. RESULTS: Of the 93 patients in the ET+ group and the 169 in the ET- group, 45 (48.4%) and 94 (55.6%) patients had MCI, respectively. The frequency of MCI subtypes between the 2 groups was different, such that 25 (55.6%) patients had nonamnestic MCI in the ET+ group and 68 (72.3%) patients had amnestic MCI in ET- group (χ=10.195, P=0.001). Compared with the MCI-ET+ group, patients in the MCI-ET- group showed more severe impairments in verbal and visuospatial memory functions. CONCLUSIONS: ET is associated with MCI, particularly the nonamnestic subtype. These results suggest that cognitive change in patients with ET may have a different pathogenesis from that of Alzheimer disease.

Relationship between the hs-CRP as non-specific biomarker and Alzheimer's disease according to aging process.

BACKGROUND: Microglia are involved in immune surveillance in intact brains and become activated in response to inflammation and neurodegeneration. Microglia have different functions, neuroprotective or neurotoxic, according to aging in patients with PD. The clinical effect of microglia in patients with Alzheimer's disease (AD) is poorly defined. This prospective study was conducted to investigate the clinical effects of microglia according to the aging process in newly diagnosed AD. METHODS: We examined 532 patients with newly diagnosed AD and 119 healthy controls, and the differences in hs-CRP between these groups were investigated. The patients with AD were classified into 3 subgroups according to age of newly diagnosed AD to investigate the relationship between hs-CRP and the aging process in newly diagnosed AD. RESULTS: There was significantly higher serum high-sensitivity C-reactive protein (hs-CRP), levels in patients with AD compared with healthy controls. A post-hoc analysis of the 3 AD subgroups showed no significant differences in serum hs-CRP level between each group. CONCLUSION: We assumed that neuroinflammation play a role in the pathogenesis of AD, but found no clinical evidence that microglia senescence underlies the microglia switch from neuroprotective in young brains to neurotoxic in aged brains. To clarify the role of microglia and aging in the pathogenesis of AD, future longitudinal studies involving a large cohort are required.