Obstructive Sleep Apnea and Striatal Dopamine Availability in Parkinson's Disease.

BACKGROUND: Sleep disorders are frequently associated with Parkinson's disease. Obstructive sleep apnea syndrome is one of these sleep disorders and is associated with the severity of motor symptoms in Parkinson's disease. Obstructive sleep apnea can lead to dopaminergic neuronal cell degeneration and may impair the clearance of α-synuclein in Parkinson's disease. Striatal dopamine uptake is a surrogate marker of nigral dopaminergic cell damage. OBJECTIVE: We aimed to investigate the differences in striatal dopamine availability between Parkinson's disease patients with or without obstructive sleep apnea. METHODS: A total of 85 de novo and nonmedicated Parkinson's disease patients were enrolled. Full-night polysomnography was performed for all patients, and obstructive sleep apnea was diagnosed as apnea/hypopnea index ≥5. Positron emission tomography was performed with 18 F-N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane, and the regional standardized-uptake values were analyzed using a volume-of-interest template and compared between groups with or without obstructive sleep apnea. RESULTS: Dopamine availability in the caudate nucleus of the obstructive sleep apnea group was significantly lower than that of the nonobstructive sleep apnea group. On subgroup analysis, such association was found in female but not in male patients. In other structures (putamen, globus pallidus, and thalamus), dopamine availability did not differ between the two groups. CONCLUSION: This study supports the proposition that obstructive sleep apnea can contribute to reduced striatal dopamine transporter availability in Parkinson's disease. Additional studies are needed to assess the causal association between obstructive sleep apnea and the neurodegenerative process in Parkinson's disease. © 2023 International Parkinson and Movement Disorder Society.

Comparison of disease progression between brain-predominant Parkinson's disease versus Parkinson's disease with body-involvement phenotypes.

Recently, new disease phenotyping has been proposed based on the origin site of α-synuclein pathology in Parkinson's disease (PD). In addition, a great deal of evidences suggested of parallel degeneration in the central nervous system and peripheral nervous system in PD. The myocardial uptake pattern of 123I-meta-iodobenzylguanidine can be a surrogate imaging biomarker for the peripheral nervous system involvement in PD. This study aimed to compare the clinical progression between brain-predominant PD (br-PD) and PD with body-involvement (bo-PD) phenotypes according to the onset of cardiac sympathetic denervation (CSD); the bo-PD group was defined as having the early onset of CSD and the br-PD phenotype was defined as those without initial CSD but later developed CSD in subsequent scans (the delayed onset of CSD). Clinical chracteristics, dopamine transporter activity, and non-motor manifestations were compared between the groups. Motor symptoms and cognitive functions at the initial and follow-up tests [3.1 (±1.4) years interval] were compared between the groups. This study included 29 br-PD and 103 bo-PD patients. Symptoms of rapid-eye-movement sleep behavior disorder, excessive daytime sleepiness, constipation, and orthostatic hypotension were more frequent in the bo-PD than in the br-PD group. The Unified Parkinson's Disease Rating Scale part III score was higher at the initial and increased more steeply during the follow-up period in the bo-PD patients than in the br-PD patients. Although the general cognitive status was not much different between the groups at initial and follow-up, each group showed statistically different cognitive domain profiles and progression patterns. The results demonstrated that the bo-PD group had more severe initial symptoms and steeper motor deterioration than the br-PD group, which indicated that there may be the more pathological involvements of central and peripheral nervous systems in the bo-PD group.

A prospective multi-centre study of susceptibility map-weighted MRI for the diagnosis of neurodegenerative parkinsonism.

OBJECTIVES: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. METHODS: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). RESULTS: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). CONCLUSIONS: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. KEY POINTS: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners.

Cortical Thickness from MRI to Predict Conversion from Mild Cognitive Impairment to Dementia in Parkinson Disease: A Machine Learning-based Model.

Background Group comparison results associating cortical thinning and Parkinson disease (PD) dementia (PDD) are limited in their application to clinical settings. Purpose To investigate whether cortical thickness from MRI can help predict conversion from mild cognitive impairment (MCI) to dementia in PD at an individual level using a machine learning-based model. Materials and Methods In this retrospective study, patients with PD and MCI who underwent MRI from September 2008 to November 2016 were included. Features were selected from clinical and cortical thickness variables in 10 000 randomly generated training sets. Features selected 5000 times or more were used to train random forest and support vector machine models. Each model was trained and tested in 10 000 randomly resampled data sets, and a median of 10 000 areas under the receiver operating characteristic curve (AUCs) was calculated for each. Model performances were validated in an external test set. Results Forty-two patients progressed to PDD (converters) (mean age, 71 years ± 6 [standard deviation]; 22 women), and 75 patients did not progress to PDD (nonconverters) (mean age, 68 years ± 6; 40 women). Four PDD converters (mean age, 74 years ± 10; four men) and 20 nonconverters (mean age, 67 years ± 7; 11 women) were included in the external test set. Models trained with cortical thickness variables (AUC range, 0.75-0.83) showed fair to good performances similar to those trained with clinical variables (AUC range, 0.70-0.81). Model performances improved when models were trained with both variables (AUC range, 0.80-0.88). In pair-wise comparisons, models trained with both variables more frequently showed better performance than others in all model types. The models trained with both variables were successfully validated in the external test set (AUC range, 0.69-0.84). Conclusion Cortical thickness from MRI helped predict conversion from mild cognitive impairment to dementia in Parkinson disease at an individual level, with improved performance when integrated with clinical variables. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Port in this issue.

Neuropsychiatric symptoms and striatal monoamine availability in early Parkinson's disease without dementia.

BACKGROUND AND OBJECTIVE: Neuropsychiatric symptoms are relatively common in Parkinson's disease (PD). Many studies have revealed that striatal monoamine availability is associated with specific neuropsychiatric symptoms. This study was aimed to investigate the association between comprehensive neuropsychiatric symptoms and striatal monoamine availability in patients with early PD without dementia. METHODS: A total of 156 newly diagnosed patients with PD without dementia were included. All patients' mental and behavioral problems were assessed with the 12-item Neuropsychiatric Inventory (NPI). They underwent positron emission tomography (PET) with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and brain magnetic resonance imaging (MRI). Patients were divided into no neuropsychiatric symptoms and neuropsychiatric symptoms groups according to total NPI score. After normalizing the PET images to spatially normalized MRI, regional standardized uptake value ratios (SUVRs) with a volume of interest template were analyzed for the two groups. RESULTS: Ninety-eight patients had more than one neuropsychiatric symptom. The SUVR of the thalamus in neuropsychiatric symptoms group was significantly lower than the SUVR in no neuropsychiatric symptoms group independent of age, sex, disease duration, or severity of motor symptoms. CONCLUSION: Patients with early PD who have neuropsychiatric symptoms had a lower monoamine availability in the thalamus than those with no neuropsychiatric symptoms. This finding suggests that decreased monoamine transporter availability in the thalamus may be an imaging biomarker of neuropsychiatric symptoms in patients with PD.

Low thalamic monoamine transporter availability is related to excessive daytime sleepiness in early Parkinson's disease.

Although excessive daytime sleepiness (EDS) is a frequent non-motor dysfunction in Parkinson's disease (PD), the exact pathophysiology remains elusive. This study investigates the relationship between daytime sleepiness and presynaptic monoamine transporter densities of the basal ganglia in patients with early PD. Sixty-four patients with early PD who were evaluated with positron emission tomography (PET) using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane were enrolled. EDS was evaluated with the Epworth Sleepiness Scale (ESS); nocturnal disabilities and nighttime sleep problems were assessed with Parkinson's Disease Sleep Scale 2nd version. PET images were normalized, and the standardized uptake value ratios (SUVRs) for caudate, putamen, globus pallidus, thalamus, and ventral striatum were obtained. The associations between regional SUVRs and ESS scores were analyzed. Among the patients studied, 12 had EDS defined as ESS > 10. The SUVR of the thalamus demonstrated a significant inverse relationship with ESS score, and thalamic monoamine availability appeared to predict EDS when controlling for covariates. The findings suggest that disrupted dopaminergic and serotonergic modulation of the thalamus may be implicated in EDS in PD. This in vivo study might contribute to elucidation of the neurobiological mechanism of hypersomnolence in PD.

"Depressed" caudate and ventral striatum dopamine transporter availability in de novo Depressed Parkinson's disease.

Depression can occur before the onset of motor symptoms in Parkinson's disease (PD) patients. The pathophysiology of depression in PD involves various brain regions and relevant functional circuits. This study investigated whether there exist distinctive patterns of presynaptic monoamine transporter densities in the basal ganglia depending on the degree of depression in patients with PD. A total of 123 early and drug-naïve PD patients were enrolled. Their affective status was evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS), and subjects were subgrouped into one of the following three groups according to their MADRS scores: no depression, mild depression, and moderate-to-severe depression. All patients underwent positron emission tomography (PET) using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane. The PET images were normalized, and differences in the regional standardized uptake value ratios (SUVRs) for each side of the caudate, putamen, globus pallidus, thalamus, and ventral striatum were analyzed and compared between the three groups. A trend analysis was performed across the groups to discern any associations between SUVR values of the basal ganglia and depression severity. The SUVR values of the caudate, anterior caudate nuclei, and ventral striatum declined as MADRS increased. The SUVR values of the striatum showed an inverse dose-dependent trend of antero- and ventroposterior gradient across the groups. This result indirectly revealed the involvement of the associative and limbic circuitry of the brain that are modulated by monoamines in early PD with depression. This might suggest an in vivo causal relationship between the ventral striatum, caudate and depression.

Excessive daytime sleepiness and its impact on quality of life in de novo Parkinson's disease.

Excessive daytime sleepiness (EDS) is one of the most common sleep problems in patients with Parkinson's disease (PD); however, its clinical implications are not clear, especially in early stage, non-medicated PD patients. This study investigated EDS in Korean patients with de novo PD and its impact on quality of life. This cross-sectional study was carried out with 198 PD patients who underwent a structured clinical interview and examination based on common and conventional scales. Motor and nonmotor symptoms were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Non-Motor Symptoms Scale (NMSS). EDS was evaluated with the Epworth Sleepiness Scale (ESS), the nocturnal disabilities and nighttime sleep problems were assessed with Parkinson's Disease Sleep Scale 2nd version, and quality of life was measured with the Parkinson's Disease Quality of Life 39 (PDQ-39). The relationships between ESS score and each scale were investigated. Among the patients studied, 42 patients had EDS defined as ESS > 10. Patients with EDS had a higher motor burden, greater nocturnal disabilities, more severe non-motor symptoms, and lower quality of life than did patients without EDS. Partial correlations revealed that ESS score was related to PDQ-39 summary index, irrespective of age, body mass index, or disease duration. These results show that EDS can have an immense negative impact on quality of life. The causes of EDS are multifactorial, which complicates its treatment. Further investigations are required to determine the safety and efficacy of potential EDS therapies and to develop novel EDS treatments in PD.

Comparison of odor identification among amnestic and non-amnestic mild cognitive impairment, subjective cognitive decline, and early Alzheimer's dementia.

Olfactory impairment might be an important clinical marker and predictor of Alzheimer's disease (AD). In the present study, we aimed to compare the degree of olfactory identification impairment in each mild cognitive impairment (MCI) subtype, subjective memory impairment, and early AD dementia and assessed the relationship between olfactory identification and cognitive performance. We consecutively included 50 patients with amnestic MCI, 28 patients with non-amnestic MCI, 20 patients with mild AD, and 17 patients with subjective memory impairment (SMI). All patients underwent clinical and neuropsychological assessments. A multiple choice olfactory identification cross-cultural smell identification test was also utilized. Controlling for age and gender, olfactory impairment was significantly more severe in patients with AD and amnestic MCI compared with the results from the non-amnestic MCI and SMI groups. Higher scores on MMSE, verbal and non-verbal memory, and frontal executive function tests were significantly related to olfactory identification ability. In conclusion, olfactory identification is impaired in amnestic MCI and AD. These findings are consistent with previous studies. In amnestic MCI patients, this dysfunction is considered to be caused by underlying AD pathology.

Validation of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Sleep.

BACKGROUND: Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD. METHODS: In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10-14 days. RESULTS: The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ. CONCLUSION: The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD.

α-Synuclein in the colon and premotor markers of Parkinson disease in neurologically normal subjects.

Extranigral non-motor signs precede the first motor manifestations of Parkinson's disease by many years in some patients. The presence of α-synuclein deposition within colon tissues in patients with Parkinson's disease can aid in identifying early neuropathological changes prior to disease onset. In the present study, we evaluated the roles of non-motor symptoms and signs and imaging biomarkers of nigral neuronal changes and α-synuclein accumulation in the colon. Twelve subjects undergoing colectomy for primary colon cancer were recruited for this study. Immunohistochemical staining for α-synuclein in normal and phosphorylated forms was performed in normally appearing colonic tissue. We evaluated 16 candidate premotor risk factors in this study cohort. Among them, ten subjects showed positive immunostaining with normal- and phosphorylated-α-synuclein. An accumulation of premotor markers in each subject was accompanied with positive normal- and phosphorylated-α-synuclein immunostaining, ranging from 2 to 7 markers per subject, whereas the absence of Lewy bodies in the colon was associated with relative low numbers of premotor signs. A principal component analysis and a cluster analysis of these premotor markers suggest that urinary symptoms were commonly clustered with deposition of peripheral phosphorylated-α-synuclein. Among other premotor marker, color vision abnormalities were related to non-smoking. This mathematical approach confirmed the clustering of premotor markers in preclinical stage of Parkinson's disease. This is the first report showing that α-synuclein in the colon and other premotor markers are related to each other in neurologically normal subjects.

Association of arterial stiffness with cognition in patients with Lewy body disorder.

The brachial-ankle pulse wave velocity (baPWV) is a marker for arterial stiffness, which is associated with cardiovascular diseases. Arterial stiffness is associated with cognitive function in the elderly and patients with Alzheimer's disease (AD). We aimed to investigate the association between arterial stiffness and cognitive function in patients with Lewy body disorder (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We consecutively included 123 patients with PD, 10 patients with DLB, and 27 AD controls. Patients with PD were divided into three groups of normal cognition (PD-NC, n = 63), mild cognitive impairment (PD-MCI, n = 43), and dementia (PD-D, n = 17). Arterial stiffness, measured as baPWV, was compared between the PD-NC, PD-MCI, PD-D, DLB, and AD patients. In LBD, we analyzed the association between arterial stiffness and each cognitive domain with adjustment for covariates. Higher baPWV was significantly associated with cognitive decline in patients with LBD (baPWV in PD-D > PD-MCI > PD-NC; DLB > PD-NC). There was no significant difference in baPWV between PD-D, DLB, and AD patients. In LBD patients, higher baPWV was associated with lower mini mental state examination score (ß ± SE = -0.003 ± 0.001, p = 0.007) and more severe dementia. Higher baPWV was also associated with lower performance in attention, language, visuospatial function, memory, and executive function in LBD patients. This suggests that vascular brain injury is associated with cognitive dysfunction in LBD.

Arterial Stiffness and Cardiovascular Autonomic Dysfunction in Patients with Parkinson's Disease.

BACKGROUND: Pulse wave velocity is a marker of arterial stiffness and a surrogate marker of vascular damage. Autonomic abnormalities associated with blood pressure are relatively commonly observed in patients with Parkinson's disease (PD). OBJECTIVE: The purpose of this study was to compare arterial stiffness between patients with PD and controls and investigate the associations between cardiovascular autonomic dysfunction and pulse wave velocity in PD. METHODS: One hundred twenty-five PD patients without diabetes mellitus were enrolled into this study, along with 22 age-matched controls. Orthostatic vital signs and ambulatory 24-hour blood pressure monitoring values were recorded. Pulse wave velocity was used to evaluate arterial stiffness. RESULTS: In PD, greater arterial stiffness was associated with orthostatic hypotension, supine hypertension, nocturnal hypertension, and nondipping. Dopaminergic treatment did not influence cardiovascular autonomic dysfunction or arterial stiffness. Although pulse wave velocity was mildly increased in patients with PD compared to controls, the arterial stiffness in PD patients without autonomic failure was similar to that in normal controls. Stiffer arteries were found only in patients with PD and autonomic failure. CONCLUSION: These findings suggest that cardiovascular autonomic dysfunction is associated with arterial stiffness in PD. PD itself does not affect arterial stiffness, whereas autonomic blood pressure disturbances influence alterations in arterial stiffness and architectural changes in the arteries of PD patients.

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.

24-Hour Ambulatory Blood Pressure Monitoring in SWEDDs Patients With Parkinsonism.

BACKGROUND: Patients diagnosed with Parkinson's disease (PD) on clinics who subsequently turn out to have normal dopamine transporter images have been referred to as scans without evidence of dopaminergic deficits (SWEDDs) patients. Cardiovascular autonomic dysfunction has frequently been reported in PD. In this study, we determined the similarities and differences in cardiac autonomic dysfunction between SWEDDs and PD patients. This study investigated whether 24-hour ambulatory blood pressure monitoring (24-hour ABPM) can help identify possible cases with SWEDDs. METHODS: We enrolled 28 SWEDDs patients, 46 patients with PD, and 30 healthy controls. To evaluate cardiac autonomic function, 24-hour ABPM was performed on all subjects. Cardiac metaiodobenzylguanidine (MIBG) scintigraphy was performed on the SWEDDs and PD subjects. RESULTS: The percentage nocturnal decline in blood pressure differed significantly among SWEDDs patients, PD patients, and controls (p<0.05). In addition to the abnormal nocturnal BP, regulation (nondipping and reverse dipping) was significantly higher in SWEDDs and PD subjects than in the control subjects (p<0.05). There was no significant correlation between the % nocturnal blood pressure reduction and parameters of cardiac MIBG uptake ratio. However, orthostatic hypotension was significant correlated with the nocturnal blood pressure dip (%), nocturnal blood pressure patterns, and the cardiac MIBG uptake ratio (early and late) in combined SWEDDs and PD subjects. CONCLUSIONS: Pathologic nocturnal blood pressure regulation and nocturnal hypertension, known characteristics of PD, are also present in SWEDDs. Moreover, cardiac sympathetic denervation should not be attributed to cardiac autonomic dysfunction in SWEDDs patients. As with PD patients, the SWEDDs patients studied here tended to have cardiac autonomic dysfunction.

Arterial stiffness and impaired renal function in patients with Alzheimer's disease.

Impaired renal function is regarded as a risk factor for vascular disease, and is associated with an increasing pulse wave velocity. Both renal dysfunction and arterial stiffness are associated with cognitive impairment and dementia. However, there have been few studies that have evaluated the relationship between albuminuria and arterial stiffness and Alzheimer's disease (AD). We investigated renal dysfunction and arterial stiffness in AD, as compared to normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). Case-control comparisons were made between 29 patients with AD, 27 with MCI, 14 with SMI, and 25 healthy controls. All patients underwent clinical and neuropsychological assessments. The urine albumin/creatinine ratio and estimated glomerular filtration rate (eGFR) were determined. Pulse wave velocity and the ankle-brachial index were used to evaluate arterial stiffness. The urine albumin/creatinine ratio and eGFR were significantly different in patients with AD, compared with the results from cognitive normal controls. The pulse wave velocity was increased and the ankle-brachial index was decreased in AD. The eGFR was well correlated with other indices and decreasing eGFR was independently associated with cognitive decline. In conclusion, albuminuria, a decreased glomerular filtration rate, an increased pulse wave velocity, and a decreased ankle-brachial index were associated with AD. These finding suggests that impaired renal functions and arterial stiffness are related to AD, in which a vascular mechanism plays a prominent role in the cognitive dysfunction associated with the disease.