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

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.

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 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.

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.

Apogeotropic central positional nystagmus as a sole sign of nodular infarction.

Positional vertigo and nystagmus without associated neurological symptoms and signs are characteristic features of benign paroxysmal positional vertigo (BPPV). Although positional nystagmus may occur with caudal cerebellar infarction including the nodulus, positional nystagmus is usually associated with other neurological signs such as spontaneous or gaze-evoked nystagmus, perverted head-shaking nystagmus, cerebellar dysmetria, or severe gait ataxia with falling. We present a patient with nodular infarction who had positional vertigo with nystagmus as a sole manifestation. Video-oculography showed apogeotropic positional horizontal nystagmus during head turning while supine, which was consistent with apogeotropic BPPV involving the horizontal canal. MRI disclosed acute infarct in the nodulus. Nodulus infarction should be considered in a patient with positional nystagmus, especially when the presenting symptoms and signs are consistent with BPPV involving the horizontal canal.

Unusual caloric responses in a patient with a fourth ventricular ependymoma.

The caloric test is probably the most widely used clinical test of vestibular function. A unilateral decrease in response to cold and warm water reliably indicates a unilateral peripheral vestibular lesion. Central signs on caloric testing are less common but important to recognize because they are often associated with lesions of the brainstem. We describe a patient with a tumor originating in the floor of the fourth ventricle who presented with premature reversal after cold stimulation on one side and perverted nystagmus after cold stimulation of the other side.

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.

Origin of isolated vertigo in rotational vertebral artery syndrome.

Rotational vertebral artery syndrome (RVAS) is characterized by recurrent attacks of paroxysmal vertigo, nystagmus, and ataxia induced by head rotation. Although recent report has described the RVAS as an important but unrecognized cause of isolated vascular vertigo, the locus of injury site responsible for isolated vertigo in RVAS is still unclear. We report here two patients with RVAS who had a stereotypic clinical presentation characterized by recurrent attacks of isolated vertigo induced by head rotation. The pattern of nystagmus observed in our patients with RVAS can be best explained by the stimulation of the vestibular labyrinth bilaterally or unilaterally. In RVAS, the isolated vertigo may occur due to transient ischemia of the superior vestibular labyrinth. RAVS should be considered in the differential diagnosis of positional vertigo, especially when vertigo is developed while sitting or standing position.

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.

Infarction in the territory of anterior inferior cerebellar artery: spectrum of audiovestibular loss.

BACKGROUND AND PURPOSE: To define the detailed spectrum of audiovestibular dysfunction in anterior inferior cerebellar artery territory infarction. METHODS: Over 8.5 years, we prospectively identified 82 consecutive patients with anterior inferior cerebellar artery territory infarction diagnosed by MRI. Each patient completed a standardized audiovestibular questionnaire and underwent a neuro-otologic evaluation, including bithermal caloric tests and pure tone audiogram. RESULTS: All but 2 (80 of 82 [98%]) patients had acute prolonged vertigo and vestibular dysfunction of peripheral, central, or combined origin. The most common pattern of audiovestibular dysfunction was the combined loss of auditory and vestibular function (n=49 [60%]). A selective loss of vestibular (n=4 [5%]) or cochlear (n=3 [4%]) function was rarely observed. We could classify anterior inferior cerebellar artery territory infarction into 7 subgroups according to the patterns of neuro-otological presentations: (1) acute prolonged vertigo with audiovestibular loss (n=35); (2) acute prolonged vertigo with audiovestibular loss preceded by an episode(s) of transient vertigo/auditory disturbance within 1 month before the infarction (n=13); (3) acute prolonged vertigo and isolated auditory loss without vestibular loss (n=3); (4) acute prolonged vertigo and isolated vestibular loss without auditory loss (n=4); (5) acute prolonged vertigo but without documented audiovestibular loss (n=24); (6) acute prolonged vertigo and isolated audiovestibular loss without any other neurological symptoms/signs (n=1); and (7) nonvestibular symptoms with normal audiovestibular function (n=2). CONCLUSIONS: Infarction in the anterior inferior cerebellar artery territory can present with a broad spectrum of audiovestibular dysfunctions. Unlike a viral cause, labyrinthine dysfunction of a vascular cause usually leads to combined loss of both auditory and vestibular functions.

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.

Ocular torsion associated with infarction in the territory of the anterior inferior cerebellar artery: frequency, pattern, and a major determinant.

BACKGROUND: Acute ischemic stroke in the distribution of the anterior inferior cerebellar artery (AICA) can cause the vestibular dysfunction in the roll plane of the vestibuloocular reflex with abnormal ocular torsion (OT). There has been no systemic study that carefully investigates the nature of OT that occurs with AICA infarction. OBJECTIVES: To investigate the frequency, the characteristic patterns of OT associated with AICA territory infarction, and the crucial site for determining the direction of OT in AICA territory infarction. METHODS: We studied 12 consecutive cases of infarction in the territory of the AICA diagnosed by brain MRI. Fundus photography, prism cover test, and subjective visual vertical tilting test were performed to evaluate the function of the otolith system. Pure tone audiogram was also performed to evaluate the function of the auditory system. RESULTS: Nine (75%) of 12 patients exhibited pathological ocular torsion (OT). Two types of pathological OT were found: ipsiversive OT accompanying skew deviation (n=6), and contraversive OT only (n=3). Six patients with ipsiversive OT with skew deviation showed an audiovestibular loss with canal paresis and hearing loss ipsilaterally whereas three patients with contraversive OT without skew deviation had a normal audiovestibular response. In all cases with pathological OT, the direction of the subjective visual vertical tilt corresponded to the direction of the OT. CONCLUSIONS: Our findings emphasize that the peripheral vestibular structure with inner ear probably plays a crucial role in determining the direction of OT associated with AICA territory infarction.

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.

Body lateropulsion as an isolated or predominant symptom of a pontine infarction.

BACKGROUND: Lateropulsion of the body--that is, falling to one side--is a well-known clinical feature of stroke in the posterior circulation. Body lateropulsion as an isolated or predominant manifestation of a pontine stroke has not been reported previously. OBJECTIVE: To elucidate the possible mechanisms of patients presenting with body lateropulsion as an isolated or predominant symptom of an isolated pontine infarction. METHODS: Between May 2004 and February 2006, out of 134 patients admitted with an isolated pontine stroke, we identified 8 (6%) consecutive patients in the Keimyung University Stroke Registry who had body lateropulsion as the main presenting symptom. RESULTS: All lesions were localised to the paramedian tegmentum just ventral to the fourth ventricle. All except one showed a uniform pattern of body lateropulsion, in which the direction of falling was away from the side of an infarct. In two patients body lateropulsion was the sole clinical manifestation, whereas the other patients had other neurological signs. All but one patient had contraversive tilting of the subjective visual vertical (SVV). In all cases, the direction of SVV tilt corresponded to the direction of body lateropulsion. The mean net tilt angle was 6.1 degrees. CONCLUSIONS: Based on the known anatomy of ascending vestibular pathways, SVV tilting and MRI findings, it is concluded that body lateropulsion probably results from damage to the graviceptive pathway ascending through the paramedian pontine tegmentum.

Reversal of the concreteness effect for verbs in patients with semantic dementia.

The authors assessed comprehension of carefully matched classes of words, manipulating grammatical subcategory (noun and verb) and semantic (concrete and abstract) characteristics for participants with semantic dementia (SD) or probable Alzheimer's disease (AD). Participants selected the best of four words that matched a verbal description. Participants with AD or SD were significantly impaired with verbs compared with nouns. Moreover, participants with SD showed significantly greater difficulty with motion verbs compared to cognition verbs. The authors argue that two factors contribute to the difficulty with motion verbs for patients with SD. First, the verb semantic network is very poorly organized relative to the noun semantic network, leaving verbs more vulnerable to a progressive neurodegenerative disease. Second, visual feature knowledge is degraded in patients with SD because of the anatomic distribution of the disease in visual association cortex, causing relatively greater difficulty for concrete verbs compared to abstract verbs.