Association between Visceral Adipose Tissue Metabolism and Cerebral Glucose Metabolism in Patients with Cognitive Impairment.

Visceral adipose tissue (VAT) dysfunction has been recently recognized as a potential contributor to the development of Alzheimer's disease (AD). This study aimed to explore the relationship between VAT metabolism and cerebral glucose metabolism in patients with cognitive impairment. This cross-sectional prospective study included 54 patients who underwent 18F-fluorodeoxyglucose (18F-FDG) brain and torso positron emission tomography/computed tomography (PET/CT), and neuropsychological evaluations. VAT metabolism was measured by 18F-FDG torso PET/CT, and cerebral glucose metabolism was measured using 18F-FDG brain PET/CT. A voxel-based analysis revealed that the high-VAT-metabolism group exhibited a significantly lower cerebral glucose metabolism in AD-signature regions such as the parietal and temporal cortices. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that VAT metabolism was negatively associated with cerebral glucose metabolism in AD-signature regions. In addition, higher VAT metabolism was correlated with poorer outcomes on cognitive assessments, including the Korean Boston Naming Test, Rey Complex Figure Test immediate recall, and the Controlled Oral Word Association Test. In conclusion, our study revealed significant relationships among VAT metabolism, cerebral glucose metabolism, and cognitive function. This suggests that VAT dysfunction actively contributes to the neurodegenerative processes characteristic of AD, making VAT dysfunction targeting a novel AD therapy approach.

Association between Visceral Adipose Tissue Metabolism and Alzheimer's Disease Pathology.

The visceral adipose tissue (VAT) has been recognized as an endocrine organ, and VAT dysfunction could be a risk factor for Alzheimer's disease (AD). We aimed to evaluate the association of VAT metabolism with AD pathology. This cross-sectional study included 54 older subjects with cognitive impairment who underwent 2-deoxy-2-[fluorine-18]-fluoro-D-glucose (18F-FDG) torso positron emission tomography (PET) and 18F-florbetaben brain PET. 18F-FDG uptake in VAT on 18F-FDG PET images was used as a marker of VAT metabolism, and subjects were classified into high and low VAT metabolism groups. A voxel-based analysis revealed that the high VAT metabolism group exhibited a significantly higher cerebral amyloid-ß (Aß) burden than the low VAT metabolism group. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that 18F-FDG uptake in VAT was significantly associated with the cerebral Aß burden (ß = 0.359, p = 0.007). In conclusion, VAT metabolism was associated with AD pathology in older subjects. Our findings suggest that VAT dysfunction could contribute to AD development.

Prognostic Factors of COVID-19 Infection in Elderly Patients: A Multicenter Study.

The outbreak of the COVID-19 pandemic is a substantial threat to the health of all populations worldwide, and old age is a robust risk factor for poor prognosis of COVID-19 infection. To reduce the fatality rate of COVID-19 infection, further understanding of elderly patients with COVID-19 is necessary. We aimed to investigate the prognostic factors in elderly patients with COVID-19. This was a multicenter and retrospective study. Overall, 340 elderly patients with COVID-19 were enrolled in 3 hospitals in Daegu, South Korea. Death and severe pneumonia requiring oxygen treatment were defined as poor clinical outcomes. Of the patients studied, 15% died and 35.2% were classified as having severe pneumonia. In binary logistic regression analysis, activities of daily living (ADL) impairment, fever during hospitalization, initial infiltration on chest radiograph, and initial increased C-reactive protein (CRP) were significantly associated with severe pneumonia (OR = 5.33, p < 0.001; OR = 3.2, p = 0.002; OR = 2.32, p = 0.044; and OR = 1.33, p < 0.001, respectively). ADL impairment, comorbidity, fever during hospitalization, and initial increased CRP were significantly associated with death (OR = 7.13, p < 0.001; OR = 3.28, p = 0.005; OR = 3.15, p = 0.032, and OR = 1.18, p < 0.001, respectively). ADL impairment, fever, and initial CRP were poor prognostic factors in elderly patients with COVID-19. Understanding these poor prognostic factors is necessary to control the disease in elderly patients.

Relationship Between Thyroid Hormone Levels and the Pathology of Alzheimer's Disease in Euthyroid Subjects.

Background: Although several studies have reported an association between thyroid dysfunction and Alzheimer's disease (AD), the effect of mild thyroid dysfunction within the normal range of thyrotropin (TSH) on the development of AD remains unclear. The aim of this study was to evaluate the association between thyroid hormones and the pathology of AD in euthyroid subjects. Methods: Sixty-nine subjects with a TSH level between 0.5 and 4.5 µIU/L who underwent 18F-florbetaben positron emission tomography were included in this prospective cross-sectional study. The levels of serum free thyroxine (fT4) and TSH were quantified using radioimmunoassay. Neuropsychological tests were performed to assess cognitive function. Differences in cerebral amyloid-ß (Aß) burden were compared between high-normal TSH (TSH ≥2.5 µIU/mL) and low-normal TSH (TSH <2.5 µIU/mL) groups. Multiple linear regression analyses, adjusted for age, sex, education level, and Neuropsychiatric Inventory scores, were performed to evaluate relationships between thyroid hormone levels and both cerebral Aß burden and cognitive function. Results: The cerebral Aß burden in the high-normal TSH group was significantly higher than in the low-normal TSH group (1.53 ± 0.31 vs. 1.35 ± 0.22, p = 0.009). The fT4 levels were negatively correlated with cerebral Aß burden (ß = -0.240, p = 0.035), and TSH levels were positively correlated with cerebral Aß burden (ß = 0.267, p = 0.020). The fT4 level was also positively associated with cognitive function, as inferred from neuropsychological test scores. Conclusions: Thyroid hormone concentrations were associated with AD pathology in euthyroid subjects. Our findings suggest that AD is likely to occur even in individuals with high-normal TSH levels.

Association between white matter lesions and the cerebral glucose metabolism in patients with cognitive impairment. / Asociación entre daños en la sustancia blanca y metabolismo de la glucosa cerebral en pacientes con disfunción cognitiva.

AIM: White matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive impairment. It has not been sufficiently evident that cognitive impairment in patients with Alzheimer's disease is caused by WMLs as well as ß-amyloid (Aß) pathology. The aim of this study was to evaluate relationship between WMLs and cerebral glucose metabolism in patients with cognitive impairment after adjustment of cerebral Aß burden. MATERIALS AND METHODS: Eighty-three subjects with cognitive performance ranging from normal to dementia, who underwent brain MRI and 18F-florbetaben positron emission tomography (PET) and 18F-fluorodeoxyglucose PET, were included in this cross-sectional study. The Fazekas scale was used to quantify WMLs on brain T2-weighted MRI. The cerebral Aß burden and cerebral glucose metabolism were quantitatively estimated using volume-of-interest analysis. Differences in the regional cerebral glucose metabolism were evaluated between low-WML (Fazekas scale<2) and high-WML (Fazekas scale≥2) groups. Multiple linear regression analysis adjusted for age, sex and cerebral Aß burden was performed to evaluate the relationship between the Fazekas scale score and cerebral glucose metabolism. RESULTS: The regional cerebral glucose metabolism for the bilateral frontal, temporal, and parietal cortices, and limbic lobes in the high-WML group were significantly lower than those in the low-WML group. There were significant negative correlations between the Fazekas scale score and regional cerebral glucose metabolism in the bilateral frontal, bilateral temporal and left parietal cortices, and bilateral limbic lobes. Multiple linear regression analysis revealed that the Fazekas scale score was an independent determinant of the glucose metabolism in the bilateral frontal and temporal cortices and limbic lobes. CONCLUSIONS: WMLs are associated with decreased cerebral glucose metabolism. Our findings suggest that small vessel disease, as well as Aß pathology, may contribute to cognitive impairment in patients with Alzheimer's disease.

Association between white matter lesions and cerebral Aß burden.

INTRODUCTION: White matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive impairment in older adults. The purpose of this study was to evaluate the association between WMLs and cerebral amyloid-ß (Aß) burden in patients with cognitive impairment. METHODS: A total of 83 patients with cognitive impairment, who underwent brain MRI and F-18 florbetaben PET, were included prospectively: 19 patients were cognitively unimpaired, 30 exhibited mild cognitive impairment (MCI), and 34 exhibited dementia. The Fazekas scale was used to quantify WMLs on T2-weighted brain MR images. Cerebral Aß burden was quantitatively estimated using volume-of-interest analysis. Differences in cerebral Aß burden were evaluated between low-WML (Fazekas scale ≤1) and high-WML (Fazekas scale ≥2) groups. The relationship between the Fazekas rating and cerebral Aß burden was evaluated using linear regression analysis after adjusting for age and sex. RESULTS: In the overall cohort, the high-WML group exhibited significantly higher Aß burden compared with the low-WML group (P = 0.011) and cerebral Aß burden was positively correlated with Fazekas rating (ß = 0.299, P = 0.006). In patients with MCI, the high-WML group exhibited significantly higher Aß burden compared with the low-WML group (P = 0.019) and cerebral Aß burden was positively correlated with Fazekas rating (ß = 0.517, P = 0.003). CONCLUSION: The presence of WMLs was associated with cerebral Aß burden in patients with MCI. Our findings suggest that small vessel disease in the brain is related to Alzheimer's disease pathology.

Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer's dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial.

BACKGROUND AND OBJECTIVE: Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. METHODS: Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. RESULTS: Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups. CONCLUSIONS: Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01380288.

Relationship between postural instability and subcortical volume loss in Alzheimer's disease.

The relationship between postural instability and subcortical structure in AD has received less attention. The aims of this study were to assess whether there are differences in the ability to control balance between Alzheimer's disease (AD) and controls, and to investigate the association between subcortical gray matter volumes and postural instability in AD.We enrolled 107 consecutive AD patients and 37 controls. All participants underwent detailed neuropsychological evaluations, T1-weighted MRI at 3 T, and posture assessment using computerized dynamic posturography. We segmented the volumes of 6 subcortical structures of the amygdala, thalamus, caudate nucleus, putamen, globus pallidus and nucleus accumbens, and of hippocampus, using the FMRIBs integrated registration and segmentation tool.All subcortical structures, except for the globus pallidus, were smaller in AD compared with controls on adjusting for age and gender. Falling frequencies in unilateral stance test (UST) and composite scores in sensory organization test (SOT) were worse in AD than in controls. The motor control test did not reveal any differences between groups. On subgroup analyses in AD, the groups with poor performance in UST or SOT exhibited significantly reduced nucleus accumbens and putamen volumes, and nucleus accumbens volume, respectively. The smaller volume of the nucleus accumbens was associated with postural instability in AD (OR [95% CI] 17.847 [2.59-122.80] for UST, 42.827[6.06-302.47] for SOT, all P < .05).AD patients exhibited reduced ability to control balance compared with controls, and this postural instability was associated with nucleus accumbens volume loss. Furthermore, cognitive dysfunction was more prominent in the group with severe postural instability.

Detailed Relationship Between the Pattern of Blood Pressure Change During the Valsalva Maneuver and the Degree of Orthostatic Hypotension During the Head-Up Tilt Test in Patients With Orthostatic Intolerance: A Retrospective Case-Control Study.

Although the head-up tilt (HUT) test and Valsalva maneuver (VM) have been widely used to identify sympathetic adrenergic impairment, the detailed relationship between the degree of orthostatic hypotension (OH) during the HUT test and the pattern of blood pressure (BP) change during the VM remains unknown. This study was performed to investigate the relationship between the degree of OH during the HUT test and the pattern of BP change during the VM. During a 4-year period, a total of 132 consecutive patients with neurogenic OH and 60 healthy controls were enrolled. The degree of OH was defined as mild (associated with a fall in systolic BP [SBP] ≥ 20 < 30 on tilting, n = 49), moderate (associated with a fall in SBP ≥ 30 < 40 on tilting, n = 43), and severe (associated with a fall in SBP ≥ 40 on tilting, n = 40). A standardized battery of autonomic tests, including the HUT test and VM using Finometer devices for recording beat-to-beat BP and heart rate response, and a quantitative sudomotor axon reflex test, was performed. Sympathetic indexes (SIs 1-6) were calculated from the VM. A composite autonomic severity score (CASS) was also obtained to evaluate the severity and distribution of autonomic dysfunction. The degree of OH was compared with the BP decline and recovery during the VM. All indexes exhibited overall significant differences among tested groups (P < 0.001). Only SI 3 differentiated all subject groups. Compared with other SIs, SI 3 was best correlated with the amount of decrease in the mean SBP (R = 0.473, P < 0.001) on tilting. The decrease in mean SBP on tilting was best correlated with CASS adrenergic subscore. SI 3 can differentiate between groups with different degrees of OH. The SI 3 obtained during VM can improve the diagnostic accuracy of autonomic dysfunction in patients with different degree of OH.

Relation between subcortical grey matter atrophy and conversion from mild cognitive impairment to Alzheimer's disease.

OBJECTIVE: To investigate whether subcortical grey matter atrophy predicts progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD), and to compare subcortical volumes between AD, MCI and controls. To assess the correlation between subcortical grey matter volumes and severity of cognitive impairment. METHODS: We included 773 participants with three-dimensional T1-weighted MRI at 3 T, made up of 181 controls, who had subjective memory symptoms with normal cognition, 201 MCIs and 391 AD. During follow-up (2.0 ± 0.9 years), 35 MCIs converted to AD (progressive MCI) and 160 MCIs remained stable (stable MCI). We segmented volumes of six subcortical structures of the amygdala, thalamus, caudate nucleus, putamen, globus pallidus and nucleus accumbens, and of the hippocampus, using FMRIBs integrated registration and segmentation tool. RESULTS: Analysis of variances, adjusted for sex and age, showed that all structures, except the globus pallidus, were smaller in AD than in controls. In addition, the amygdala, thalamus, putamen, nucleus accumbens and hippocampus were smaller in MCIs than in controls. Across groups, all subcortical greymatter volumes, except the globus pallidus, showed a positive correlation with cognitive function, as measured by Mini Mental State Examination (MMSE) (0.16

Failure of Fixation Suppression of Spontaneous Nystagmus in Cerebellar Infarction: Frequency, Pattern, and a Possible Structure.

To investigate the frequency and pattern of failure of the fixation suppression (FFS) of spontaneous nystagmus (SN) in unilateral cerebellar infarction, and to identify the structure responsible for FFS, 29 patients with acute, mainly unilateral, isolated cerebellar infarction who had SN with a predominantly horizontal component were enrolled in this study. The ocular fixation index (OFI) was defined as the mean slow phase velocity (SPV) of the horizontal component of SN with fixation divided by the mean SPV of the horizontal component of SN without fixation. The OFI from age- and sex-matched patients with vestibular neuritis was calculated and used as the control data. The FFS of SN was only found in less than half (41 %, 12/29) of the patients. Approximately 65 % (n = 7) of the patients with isolated anterior inferior cerebellar artery territory cerebellar infarction showed FFS, whereas only a quarter (n = 3) of the patients with isolated posterior inferior cerebellar artery (PICA) territory cerebellar infarction showed FFS. The proportion of gaze-evoked nystagmus (6/12 [50 %] vs. 2/17 [12 %], p = 0.04) and deficient gain of ipsilesional pursuit (10/12 [83 %] vs. 6/17 [35 %], p = 0.05) was more frequent in the FFS group than in the group without FFS. Lesion subtraction analysis in isolated PICA territory cerebellar infarction revealed that the nodulus was commonly damaged in patients with FFS, compared to that of patients without FFS. Our study shows that FFS of SN due to acute cerebellar infarction is less common than previously thought and the nodulus may be an important structure for the suppression of SN in humans.

Recent Advances in Cerebellar Ischemic Stroke Syndromes Causing Vertigo and Hearing Loss.

Cerebellar ischemic stroke is one of the common causes of vascular vertigo. It usually accompanies other neurological symptoms or signs, but a small infarct in the cerebellum can present with vertigo without other localizing symptoms. Approximately 11 % of the patients with isolated cerebellar infarction simulated acute peripheral vestibulopathy, and most patients had an infarct in the territory of the medial branch of the posterior inferior cerebellar artery (PICA). A head impulse test can differentiate acute isolated vertigo associated with PICA territory cerebellar infarction from more benign disorders involving the inner ear. Acute hearing loss (AHL) of a vascular cause is mostly associated with cerebellar infarction in the territory of the anterior inferior cerebellar artery (AICA), but PICA territory cerebellar infarction rarely causes AHL. To date, at least eight subgroups of AICA territory infarction have been identified according to the pattern of neurotological presentations, among which the most common pattern of audiovestibular dysfunction is the combined loss of auditory and vestibular functions. Sometimes acute isolated audiovestibular loss can be the initial symptom of impending posterior circulation ischemic stroke (particularly within the territory of the AICA). Audiovestibular loss from cerebellar infarction has a good long-term outcome than previously thought. Approximately half of patients with superior cerebellar artery territory (SCA) cerebellar infarction experienced true vertigo, suggesting that the vertigo and nystagmus in the SCA territory cerebellar infarctions are more common than previously thought. In this article, recent findings on clinical features of vertigo and hearing loss from cerebellar ischemic stroke syndrome are summarized.

Recent advances in orthostatic hypotension presenting orthostatic dizziness or vertigo.

Orthostatic hypotension (OH), a proxy for sympathetic adrenergic failure, is the most incapacitating sign of autonomic failure. Orthostatic dizziness (OD) is known to be the most common symptom of OH. However, recent studies have demonstrated that 30-39 % of patients with OH experienced rotatory vertigo during upright posture (i.e., orthostatic vertigo, OV), which challenges the dogma that OH induces dizziness and not vertigo. A recent population-based study on spontaneously occurring OD across a wide age range showed that the one-year and lifetime prevalence of OD was 10.9 and 12.5 %, respectively. Approximately 83 % of patients with OD had at least one abnormal autonomic function test result. So far, 11 subtypes of OD have been proposed according to the pattern of autonomic dysfunction, and generalized autonomic failure of sympathetic adrenergic and parasympathetic cardiovagal functions was the most common type. Four different patterns of OH, such as classic, delayed, early, and transient type have been found in patients with OD. The head-up tilt test and Valsalva maneuver should be performed for a comprehensive evaluation of sympathetic adrenergic failure in patients with OD/OV. This review summarizes current advances in OH presenting OD/OV, with a particular focus on the autonomic dysfunction associated with OD.

Long-term prognosis for hearing recovery in stroke patients presenting vertigo and acute hearing loss.

BACKGROUND AND PURPOSE: Vertebrobasilar ischemic stroke (VBIS) can cause acute hearing loss (AHL) because the vertebrobasilar system supplies most of the auditory system including the inner ear. The aim of this study was to assess the long-term prognosis of AHL associated with VBIS. METHODS: Over 12.5 years, 62 patients with AHL of a vascular cause who were followed for at least 1 year (mean, 49.2 months; SD, 24.4 months) were enrolled in this study. Quantitative audiovestibular function testing was performed during the acute (mostly within 10 days after symptom onset) and last follow-up periods in all patients. RESULTS: On the last follow-up, approximately 65% (39/62) of the patients showed a partial (n=24) or complete (n=15) hearing recovery. All but 2 (97%) patients had acute vertigo and 56 (56/62, 90%) had a unilateral canal paresis to caloric stimulation on the side of the AHL. The most commonly infarcted territory on brain MRI was in the distribution of the anterior inferior cerebellar artery (55/62, 89%). Multivariable analysis showed that multiple risk factors for stroke [odds ratio (OR) 10.46, 95% confidence interval (CI) 1.72 to 13.7, p=0.011] and profound hearing loss [OR 3.92, 95% CI 1.03 to 14.97, p<0.046] predicted a poor outcome for recovery of hearing loss. CONCLUSIONS: Acute hearing loss associated with posterior circulation ischemic stroke exhibits a relatively good long-term outcome. Two or more risk factors for stroke and profound hearing loss are adverse prognostic factors for recovery of hearing loss of a vascular cause.

Spectrum of autonomic dysfunction in orthostatic dizziness.

OBJECTIVE: To investigate the frequency and detailed spectrum of autonomic dysfunction in patients with orthostatic dizziness (OD). METHODS: Over 20 months, 217 consecutive patients with OD as a presenting symptom of orthostatic intolerance were enrolled. The distribution and severity of autonomic dysfunction were measured by the composite autonomic severity score (CASS), which was derived from a standard autonomic function test including Finapres for recording of the beat-to-beat blood pressure. Sympathetic indexes (SIs) were calculated from the Valsalva maneuver (VM). RESULTS: Approximately 83% of patients showed at least one abnormal autonomic testing result. We classified OD into 11 groups according to the patterns of autonomic dysfunctions. The most common pattern was generalized autonomic failure of sympathetic adrenergic and parasympathetic cardiovagal functions (n=60). Patients with delayed OH had larger BP increases during late phase II of the VM (p=0.04), showed greater phase IV overshoot (p=0.04), and had a smaller pressure recovery time increase (p=0.02) than patients with classic OH. Each SI showed the strongest correlation with the CASS adrenergic subscores. CONCLUSIONS: OD can present with a board spectrum of autonomic dysfunctions. SIGNIFICANCE: This investigation could be useful in understanding the pattern and mechanism of autonomic dysfunction associated with OD.

Hyperventilation-induced nystagmus in vestibular neuritis: pattern and clinical implication.

BACKGROUND: It was the aim of this study to investigate the pattern of evolution of hyperventilation-induced nystagmus (HIN) in vestibular neuritis (VN) and to determine whether HIN influences the dizziness outcome at the last follow-up visit. METHODS: Fifty-three consecutive patients with VN underwent a quantitative vestibular function test including hyperventilation and the Korean version of the Dizziness Handicap Inventory during the acute period and the follow-up visit. RESULTS: The incidence of HIN was higher in the acute (62%, 33/53) than in the chronic (17%, 9/53) stages of VN. Approximately 70% (6/9) of patients who continued to have persistent HIN at the last follow-up reported dizziness compared to only 27% (12/44) of patients who had no HIN. Patients who complained of persistent dizziness were significantly more likely to have persistent HIN and high Korean Dizziness Handicap Inventory scores at the last follow-up compared with patients who did not suffer from dizziness. In terms of the degree of recovery of dizziness, patients with HIN initially beating toward the contralesional side exhibited significantly more improvement than patients with HIN initially beating toward the ipsilesional side. CONCLUSIONS: The presence of either HIN beating toward the ipsilesional side at the acute stage of VN or persistent HIN at the follow-up visit is associated with persistent dizziness.

Response to rivastigmine transdermal patch or memantine plus rivastigmine patch is affected by apolipoprotein E genotype in Alzheimer patients.

BACKGROUND/AIMS: The apolipoprotein E (APOE) genotype in response to pharmacological treatments in patients with Alzheimer's disease (AD) remains a matter of controversy. This analysis investigated the effect of the APOE genotype on the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine patch in patients with mild to moderate AD. METHODS: Two hundred and six (n = 206) patients with probable AD and Mini-Mental State Examination (MMSE) scores of 10-20 were randomized to rivastigmine patch monotherapy or memantine plus rivastigmine patch for 24 weeks. Of the 206 patients with probable AD, 146 patients who consented to genetic testing for APOE were included and assessed for this subgroup study. RESULTS: There were no significant differences on MMSE, NPI, ADAS-cog, ADCS-ADL, CDR-SB, NPI and FAB between rivastigmine patch monotherapy and memantine plus rivastigmine patch according to the APOE genotype. However, patients with moderately severe AD (MMSE ≤15) who were APOE ε4 carriers showed higher responder rates on ADCS-ADL with memantine plus rivastigmine patch compared to rivastigmine patch monotherapy. CONCLUSION: Moderately severe AD patients with the APOE ε4 allele may respond more favorably to memantine plus rivastigmine patch than ε4 noncarriers.