Group- and Home-Based Cognitive Intervention for Patients with Mild Cognitive Impairment: A Randomized Controlled Trial.

BACKGROUND: We examined the efficacy of group-based cognitive intervention (GCI) and home-based cognitive intervention (HCI) in amnestic mild cognitive impairment (aMCI) and intervention effects on serum brain-derived neurotrophic factor (BDNF). METHODS: In this randomized and rater-blinded trial, 293 patients with aMCI from 18 nationwide hospitals were randomized: 96 to the GCI group, 98 to the HCI group and 99 to the control group. For 12 weeks, subjects receiving GCI participated twice per week in group sessions led by trained instructors, and those receiving HCI completed homework materials 5 days per week. They were assessed at baseline, postintervention (PI) and at the 6-month follow-up after the intervention. The primary endpoint was the change from baseline to PI in the modified Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog). RESULTS: In comparison to the controls (a 0.8-point decrease), the subjects receiving GCI (a 2.3-point decrease, p = 0.01) or HCI (a 2.5-point decrease, p = 0.02) showed significant improvements in the modified ADAS-Cog at PI, respectively. By the 6-month follow-up, those receiving GCI or HCI had better scores in the modified ADAS-Cog than the controls. The changes in BDNF levels significantly correlated with the changes in the modified ADAS-Cog in the GCI (r = -0.29, p = 0.02 at PI) and HCI (r = -0.27, p = 0.03 at 6-month follow-up) groups, respectively. CONCLUSIONS: The GCI and HCI resulted in cognitive improvements in aMCI. An enhanced brain plasticity may be a component of the mechanism underpinning the cognitive improvements associated with the cognitive interventions.

Microstructural changes in the hippocampus and posterior cingulate in mild cognitive impairment and Alzheimer's disease: a diffusion tensor imaging study.

Diffusion tensor imaging (DTI) is a sensitive MRI technique in the detection of white matter degeneration. We sought to demonstrate microstructural changes in normal controls, patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) and to determine which DTI parameters could be a reliable tool for the early diagnosis of AD. In total, 90 participants (35 normal, 20 aMCI, 35 AD) were recruited. We included early AD patients with clinical dementia rating scores of 0.5 and 1. The fractional anisotropy and mean diffusivity values, DTI parameter, were measured with the regions of interest method in the bilateral hippocampal body and posterior cingulate. Clinical history, neurological examination, and neuropsychological assessments were conducted. The DTI parameters in the bilateral hippocampus and posterior cingulate in aMCI and AD were different from those in normal controls. No difference was found in DTI parameters of the posterior cingulate between aMCI and AD. However, hippocampal DTI parameters were different between aMCI and AD. Cognitive summary measures were significantly correlated with DTI parameters, especially FA values in the hippocampus. The DTI analysis technique demonstrated significant microstructural alterations in the hippocampus and posterior cingulate already in prodromal stage of AD. DTI parameters in the hippocampus may be a more sensitive method to determine microstructural changes in early AD states and more correlated with cognition than DTI parameters in the posterior cingulate.

Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI).

The Neuropsychiatric Inventory (NPI) is used to assess neuropsychiatric symptoms in dementia patients. To reduce clinicians' time taken to administer the NPI, the authors studied a caregiver-administered NPI (CGA-NPI), in which caregivers completed the written form of the NPI worksheet. After a brief presupervision session, the caregivers of 61 dementia patients completed the CGA-NPI by reading through the worksheet. This was followed by a postsupervision session to check if the caregivers had completed the form appropriately. The correlation between the prevalence rates of each neuropsychiatric symptom obtained by the CGA-NPI and those obtained by the NPI was fair to good (kappa = 0.57-0.90) in all domains. All frequency, severity, and caregivers' distress scores of the CGA-NPI correlated significantly with those of the NPI (r> 0.6, P<.001). Total CGA-NPI scores also correlated highly with total NPI scores (r= 0.86, P<.001). These results suggest that the CGA-NPI can substitute for the NPI, saving administration time.

Do Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD) progress differently?

Our study aimed to compare cognitive status and declines in AD with/without small vessel disease (SVD) and SIVD at baseline and 1-year follow-up. Patients with Alzheimer's disease without small vessel disease (AD(-)SVD) (n=148), Alzheimer's disease with small vessel disease (AD(+)SVD) (n=94) and SIVD (n=60) were recruited from database of multiple centers in Korea. Basic demographics and detailed neuropsychological results were compared. AD, regardless of SVD, showed worse memory and better executive function than SIVD at baseline. Mini-Mental State Examination scores and visual memory function declined more in AD than those in SIVD whereas Barthel Activities of Daily Living (B-ADL) scores declined more in SIVD. AD showed different patterns of cognitive impairment compared with SIVD. After 1 year, AD showed more rapid cognitive decline in some domains. Further investigations with longer follow-up duration may be needed to confirm the cumulative effects of SVD in AD and different patterns of decline between AD and SIVD.

Functional assessment staging (FAST) in Korean patients with Alzheimer's disease.

Functional Assessment Staging (FAST) was devised to meet the need for a more brief patient-derived rating scale for evaluating changes in functional performance and activities of daily living skills in all the stages of Alzheimer's disease (AD). FAST was administered to 464 patients with probable AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. The patients were also evaluated using the Korean version of the Mini-Mental Status Examination (K-MMSE), the Clinical Dementia Rating (CDR), the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Global Deterioration Scale (GDS), the Barthel Activities of Daily Living (B-ADL), and the Seoul-Instrumental Activities of Daily Living (S-IADL). For patients with moderate to severe dementia, the Korean versions of the Severe Impairment Battery (SIB-Ko) and Baylor profound mental status examination (BPMSE-Ko) were also administered. There were significant correlations between the FAST and the K-MMSE scores (r= - 0.71, p< 0.001), between the FAST and the SIB-Ko scores (r= - 0.54, p< 0.001) and between the FAST and the BPMSE-Ko scores (r=- 0.46, p< 0.001). The FAST was also correlated with the CDR, the CDR-SB, the B-ADL, and the S-IADL (p< 0.001). Ultimately, FAST is a reliable and valid assessment technique for evaluating functional deterioration in AD patients throughout the disease course. Moreover, the findings of the present study suggest that the FAST elucidates a characteristic pattern of progressive, ordinal, and functional decline in AD in Korean AD patients with dementia.

Two cases of discontinuation syndrome following cessation of memantine.

Although memantine is widely used and generally considered safe, an abrupt cessation of memantine may result in discontinuation syndrome that can be distressing and result in decline of natural course. We report two patients who developed significant behavior disturbance after abrupt cessation of memantine. Although re-trial of memantine improves these symptoms, more additional drugs may be required to achieve previous status. Therefore, abrupt cessation of memantine should be prudent and require cautious follow up.

Cerebellar Hypoperfusion during Transient Global Amnesia: An MRI and Oculographic Study.

BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is characterized by sudden anterograde and retrograde amnesia lasting for up to 24 hours. Diffusion-weighted magnetic resonance imaging (DWI) in cases of TGA and ischemia demonstrates a high frequency of high signal intensities restricted to the hippocampus, and this has been proposed as an etiology of TGA. The aims of this study were to characterize the DWI and single-photon-emission computed tomography (SPECT) findings during the acute and recovered phases of TGA and to correlate the findings with oculomotor abnormalities. METHODS: Five consecutive patients with a clinical diagnosis of TGA underwent DWI and SPECT of the brain within 24 hours after symptom onset and again 3 days later. Eye movements were also recorded using three-dimensional video-oculography. RESULTS: In all patients, DWI disclosed small punctuate (1-3 mm), high-signal lesions in the lateral portion of the hippocampus. The initial SPECT also revealed hypoperfusion in the cerebellar vermis, which had recovered by the follow-up examination. Three patients showed saccadic hypermetria or impaired smooth pursuit only during the acute phase. CONCLUSIONS: Our patients with TGA showed cerebellar vermian hypoperfusion in addition to ischemic insults to the lateral hippocampus. The oculomotor abnormalities observed in our patients support the occurrence of cerebellar dysfunction during the TGA attack.

Associated conditions and clinical significance of awake bruxism.

BACKGROUND: Awake bruxism is defined as an oral parafunctional activity that includes clenching and grinding of teeth during wakefulness. Confirming the possible related anatomy and the clinical significance of awake bruxism in geriatric hospitals is the aim of this study. METHODS: We analyzed the medical records of 503 patients who were admitted to hospital from April to June 2008. After the recognition of bruxism, the clinical, brain imaging studies and statistical parametric mapping (SPM) of brain single photon emission computed tomography were performed. RESULTS: In each disease group, five of 125 Alzheimer's disease (AD) patients (4.0%), three of 11 frontotemporal dementia (FTD) patients (27.3%), seven of 230 stroke patients (including two patients related to citalopram, 3.0%), one of 45 Parkinson's disease patients (2.2%) and four of 17 hydrocephalus patients (23.5%) had bruxism. Even though awake bruxism occurred early after stroke onset, it occurred late after AD and FTD onset. This occurred in a far advanced stage of AD, while it occurred in a moderately advanced stage of FTD. SPM analysis in AD and FTD patients with awake bruxism revealed significant hypoperfusion in frontotemporal and other subcortical structures. Surface electromyography recordings from the masseter muscle showed rhythmic regular motor activity at a rate of 1-2/s. CONCLUSION: This study suggests that awake bruxism is encountered not infrequently in various diseases in geriatric hospitals. It is frequently observed in FTD and normal pressure hydrocephalus, which characteristically shows frontal lobe dysfunction. These facts and SPM analysis show that awake bruxism can be regarded as a frontal neurological sign of various neurological disorders.