The Effect of Cognitive Training in Patients with Mild Cognitive Impairment and Early Alzheimer's Disease: A Preliminary Study

Background and Purpose

The objective of this study was to determine the benefits of cognitive training in patients with amnestic mild cognitive impairment (aMCI) and those with early Alzheimer''s disease (AD).

Methods

Eleven patients with aMCI and nine with early AD (stage 4 on the Global Deterioration Scale) participated in this study. Six participants with aMCI and six with AD were allocated to the cognitive training group, while five participants with aMCI and three with AD were allocated to a wait-list control group. Multicomponent cognitive training was administered in 18 weekly, individual sessions. Outcome measures were undertaken at baseline, and at 2 weeks and 3 months of follow-up.

Results

In the trained MCI group, there were significant improvements in the delayed-recall scores on the Seoul Verbal Learning Test at both the 2-week and 3-month follow-ups compared with baseline (baseline, 1.6±1.5; 2 weeks, 4.4±1.5, p=0.04; 3 months, 4.6±2.3, p=0.04). The phonemic fluency scores (1.0±0.8 vs. 5.0±1.8, p=0.07) and Korean Mini-Mental State Examination scores (18.8±0.5 vs. 23.8±2.2, p=0.07) also showed a tendency toward improvement at the 2-week follow-up compared to baseline in the trained AD group.

Conclusions

This study provides evidence of the effectiveness of cognitive training in aMCI and early AD. The efficacy of cognitive training programs remains to be verified in studies with larger samples and a randomized design.     

Prevalence of Alzheimer's Dementia and Its Risk Factors in Community-Dwelling Elderly Koreans

Objective

We estimated the prevalence of Alzheimer''s dementia (AD) and mild cognitive impairment (MCI) and their risk factors in an urban community setting, focusing especially on metabolic syndrome.

Methods

A two-phase investigation based on a door-to-door survey was performed. In Phase I, we administered the Korean version of the Mini-Mental State Examination (MMSE-KC) of the Consortium to Establish a Registry for Alzheimer''s disease (CERAD-K). Assessment Packet and the Korean version of the Geriatric Depression Scales (GDS-K) to all 706 participants aged 65 years or older. In Phase II of the study, 175 persons underwent physical and neurological examinations according to the protocol of the CERAD-K clinical assessment battery [CERAD-K (C)] and the neuropsychological assessment battery [CERAD-K (N)]. We also examined the association between cognitive decline and metabolic syndrome. AD and MCI were defined using the DSM-IV-TR criteria and the Clinical Dementia Rating (CDR) scales.

Results

The mean age (±SD) of the subjects was 74.3±16.7 years and the ratio of males to females was 53.2 to 46.8. The prevalence of Alzheimer''s dementia was 9.0%, while that of MCI was 32.9%. Old age and lower educational level had significant associations with cognitive decline in the elderly, but gender, years of alcohol intake or smoking, and metabolic syndrome were not associated with AD or MCI.

Conclusion

In this study, metabolic syndrome was not associated with Alzheimer''s AD or MCI. Information regarding an association between Alzheimer''s dementia and metabolic syndrome in this study will be helpful in formulating future public health policy and prevention strategies in Korea.     

Cognitive profiles in Mild Cognitive Impairment (MCI) patients associated with Parkinson's disease and cognitive disorders

Background:

Mild cognitive impairment (MCI) is rapidly becoming one of the most common clinical manifestations affecting the elderly and represents an heterogeneous clinical syndrome that can be ascribed to different etiologies; the construct of MCI in Parkinson''s disease (PD) (MCI-PD) is more recent but the range of deficits is still variable. Early recognition and accurate classification of MCI-PD could offer opportunities for novel therapeutic interventions to improve the natural pathologic course.

Objective:

To investigate the clinical phenotype of amnestic mild cognitive impairment (aMCI) and in patients with PD and MCI (MCI-PD).

Materials and Methods:

Seventy-three patients with aMCI and in 38 patients with MCI-PD were enrolled. They all underwent Mini–mental State Examination (MMSE), the Rey auditory-verbal learning test and the immediate visual memory (IVM) item of the Mental Deterioration Battery, the Rey auditory-verbal learning test included the Rey-immediate (Rey-I), and the delayed recall of the word list (Rey test deferred, Rey-D). The Geriatric Depression Scale (GDS) was used for mood assessment.

Results:

The results of the Rey-I and Rey-D and of the IVM item showed statistically significant differences between the aMCI and the MCI-PD group. The mean Rey-I and Rey-D score was significantly lower as well as the IVM score was higher in patients with aMCI than in those with MCI-PD, aMCI patients showed greater impairment in long-term memory, whereas more aMCI than MCI-PD patients had preserved attention, computation, praxis, and conceptualization.

Conclusions:

Our findings demonstrate that the cognitive deficit profile is specific for each of the two disorders: Memory impairment was a typical feature in aMCI patients while MCI-PD patients suffered from executive functions and visuospatial attention deficits.     

Sleep Disturbances and Predictive Factors in Caregivers of Patients with Mild Cognitive Impairment and Dementia

Background and Purpose

We examined the characteristics of sleep disturbances and sleep patterns in the caregivers of patients with amnestic mild cognitive impairment (aMCI) and dementia.

Methods

We prospectively studied 132 patients (60 with aMCI and 72 with dementia) and their caregivers, and 52 noncaregiver controls. All caregivers and controls completed several sleep questionnaires, including the Pittsburgh Sleep Quality Index (PSQI). The patients were administered neuropsychological tests and the neuropsychiatric inventory to evaluate their behavioral and neuropsychiatric symptoms of dementia (BPSD).

Results

The PSQI global score was 6.25±3.88 (mean±SD) for the dementia caregivers and 5.47±3.53 for the aMCI caregivers. The Insomnia Severity Index (ISI) and short form of the Geriatric Depression Scale (GDS-S) predicted higher PSQI global scores in aMCI caregivers, and higher scores for the ISI, Epworth Sleepiness Scale (ESS), and GDS-S in dementia caregivers. BPSD, including not only agitation, depression, and appetite change in dementia patients, but also depression, apathy, and disinhibition in aMCI patients, was related to impaired sleep quality of caregivers, but nighttime behavior was not. Age and gender were not risk factors for disturbed sleep quality.

Conclusions

Dementia and aMCI caregivers exhibit impaired quality of sleep versus non-caregivers. ISI, GDS-S, and ESS scores are strong indicators of poor sleep in dementia caregivers. In addition, some BPSD and parts of the neuropsychological tests may be predictive factors of sleep disturbance in dementia caregivers.     

Automated Classification to Predict the Progression of Alzheimer's Disease Using Whole-Brain Volumetry and DTI

Objective

This study proposes an automated diagnostic method to classify patients with Alzheimer''s disease (AD) of degenerative etiology using magnetic resonance imaging (MRI) markers.

Methods

Twenty-seven patients with subjective memory impairment (SMI), 18 patients with mild cognitive impairment (MCI), and 27 patients with AD participated. MRI protocols included three dimensional brain structural imaging and diffusion tensor imaging to assess the cortical thickness, subcortical volume and white matter integrity. Recursive feature elimination based on support vector machine (SVM) was conducted to determine the most relevant features for classifying abnormal regions and imaging parameters, and then a factor analysis for the top-ranked factors was performed. Subjects were classified using nonlinear SVM.

Results

Medial temporal regions in AD patients were dominantly detected with cortical thinning and volume atrophy compared with SMI and MCI patients. Damage to white matter integrity was also accredited with decreased fractional anisotropy and increased mean diffusivity (MD) across the three groups. The microscopic damage in the subcortical gray matter was reflected in increased MD. Classification accuracy between pairs of groups (SMI vs. MCI, MCI vs. AD, SMI vs. AD) and among all three groups were 84.4% (±13.8), 86.9% (±10.5), 96.3% (±4.6), and 70.5% (±11.5), respectively.

Conclusion

This proposed method may be a potential tool to diagnose AD pathology with the current clinical criteria.     

Decreased Serum Brain-Derived Neurotrophic Factor Levels in Elderly Korean with Dementia

Objective

The primary purpose of this study was to investigate the differences in the serum brain-derived neurotrophic factor (BDNF) level between elderly Korean people over 65 years with and without dementia.

Methods

171 individuals over 65 years were enrolled in this study. Screening for cognitive impairments was carried out using the Mini-Mental Status Examination-Korean version (MMSE-KC). One hundred thirty-two subjects scored below 1.5 standard deviations (SD) of the mean MMSE-KC score, and these were evaluated using the Consortium to Establish a Registry for Alzheimer''s Disease, Korean version (CERAD-K) and the Geriatric Depression Scale (GDS). The Clinical Dementia Rating Scale (CDRS) and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria were used for further evaluation. Subjects with a CDRS score of 1 or higher were classified as having Alzheimer''s disease (AD), and subjects with a CDRS score of 0.5 were classified as having a mild cognitive impairment (MCI). Subjects with a CDRS score of 0 were classified as having aging-associated cognitive decline (AACD). Serum BDNF levels were analyzed using the enzyme-linked immunosorbent assay (ELISA) method.

Results

The serum BDNF levels were significantly lower in the subjects with MCI and AD compared with the healthy controls (p<0.01). A significant correlation was found between the total MMSE-KC score and serum BDNF level (r=0.295; p<0.01). However, no significant correlation was observed between the severity of MMSE-KC and the total GDS score. A significant difference was found in the total score of GDS between the AACD group and subjects with AD (p<0.05).

Conclusion

This study suggested that BDNF might be involved in the pathophysiology of cognitive decline in elderly people.     

Cognitive Impairment in Parkinson's Disease without Dementia: Subtypes and Influences of Age

Background and Purpose

Cognitive impairments are common in Parkinson''s disease (PD), although the severity of these impairments does not significantly impair the patient''s daily activities. The aim of this study was to determine the frequency of mild cognitive impairment (MCI) of Parkinson''s disease (PDMCI) and its subtypes in nondemented PD patients. We also evaluated the influence of age on the pattern of subtypes of PDMCI.

Methods

A total of 141 consecutive, nondemented PD patients underwent a comprehensive neuropsychological assessment covering the five cognitive domains: attention, language, visuospatial, memory, and executive functions. PDMCI was defined as impaired performance in at least one of these five cognitive domains. The influence of age on the distribution of subtypes of PDMCI was assessed by comparing patients in two groups dichotomized according to their age at assessment (younger vs. older).

Results

Fifty-seven (40.4%) of the nondemented PD patients had an impairment in at least one domain, and were therefore considered as having PDMCI. The age at assessment and age at disease onset were significantly higher in the PDMCI patients. The amnestic type of PDMCI was the most frequent, followed by the visuospatial, linguistic, executive, and attention types in that order. The frequency of PDMCI was higher for all subtypes in the older group; the domain that was influenced the most by age was executive function.

Conclusions

MCI was common in PD and the subtypes were diverse. Age was found to be an important risk factor for the development of PDMCI, particularly for the executive subtype. These results indicate that the concept of MCI should be introduced in PD.     

A cross-sectional study on thyroid status in North Indian elderly outpatients with dementia

Background:

Several population based studies have demonstrated an association between hypo-or hyperthyroidism and dementia in last two decades. As a consequence, thyroid stimulating hormone has become part of the screening laboratory test for dementia.

Aim:

The aim of the present study was to evaluate the association between thyroid function and Alzheimer''s disease (AD) and vascular dementia (VaD) and to determine the risk of AD and VaD in clinically euthyroid patients.

Materials and Methods:

A cross-sectional hospital based study was carried out in subjects diagnosed with AD/VaD and were assessed for thyroid status as routine screening test.

Results:

Free T3, free T4 and TSH were studied in 114 AD patients (mean age: 65 years), 35 VaD patients (mean age: 62 years) and 105 control subjects (mean age: 62 years). In AD group, TSH levels were significantly lower than controls (P = 0.00) and for each unit increase in TSH level, the odds of having dementia decreased by 37.1%. No such relation was seen in VaD.

Conclusion:

The results suggest a consistent association of subclinical hyperthyroidism and AD.     

A preliminary study of the Six-Item Screener in detecting cognitive impairment

Objective

The present retrospective study was to explore the clinical value of Six-Item Screener (SIS), which is constituted by 6 items from mini-mental status examination (MMSE), to identify cognitive impairment.

Methods

A total number of 1976 patients aged over 50 years, from the Memory Clinic of Huashan Hospital were employed in a battery of neuropsychological tests including MMSE. Subjects with severe conditions, unable to cooperate, or having been previously enrolled, were excluded from this study. The employed subjects were divided into 3 groups: subjective memory complaints (SMCs) (475 cases), patients with mild cognitive impairment (MCI) (440 cases), and patients with Alzheimer’s disease (AD) (1061 cases, including 555 mild, 339 moderate, and 167 severe). A total score of MMSE and a score of SIS composed of date, month, year, three-word delayed recall from MMSE were calculated. Data were analyzed based on educational background.

Results

The cut-off of SIS score was ⩽ 2 for illiterate, ⩽ 3 for elementary, and ⩽ 4 for junior high school or above. The sensitivity and specificity of SIS for detecting mild AD were 88.5% and 78.3%, respectively, with an overall accuracy of 83.8%, while for detecting MCI, the sensitivity and specificity were 34.3% and 90.1%, respectively, with an overall accuracy of 63.2%.

Conclusion

SIS is an effective and reliable instrument for dementia detection in outpatient department. However, it has limited value for MCI identification.     

The role of the Montreal Cognitive Assessment (MoCA) and its memory tasks for detecting mild cognitive impairment

To investigate the role of the Montreal Cognitive Assessment (MoCA) (Beijing version) and its memory tasks on detecting different mild cognitive impairment (MCI) subtypes including amnestic MCI (aMCI) and nonamnestic MCI (naMCI) in memory clinics. A total of 121 patients with MCI and 53 healthy controls were included. Fifty-six aMCI-multiple domains (amMCI), 32 aMCI-single domain (asMCI), and 33 naMCI patients were diagnosed according to extensive cognitive tests. All participants were administered by the Mini Mental State Examination (MMSE) and the MoCA. Patients with amMCI performed worse than patients with asMCI, naMCI, and healthy controls on the MMSE and the MoCA (p <?0.001). The area under the curve (AUC) value for the MoCA when comparing the amMCI and control groups was 0.884 (p?<?0.001), which was superior to that of the MMSE. The AUC value decreased to 0.687 when applied to the naMCI and control groups (p?=?0.007), which was still higher than that of the Rey Auditory Verbal Learning Test (RAVLT) or the Rey-Osterrieth complex figure (ROCF). Delayed free recall or category prompted recall in the MoCA had roles in differentiating asMCI and controls groups with AUC value of 0.717 (p =?0.002) and 0.691 (p =?0.005), respectively. The MoCA is a good screening tool for detecting different types of MCI and is suitable for patients in outpatient clinics.     

Medial Temporal Atrophy and Memory Dysfunction in Poststroke Cognitive Impairment-No Dementia

Background and Purpose

It was recently reported that the prevalence of poststroke memory dysfunction might be higher than previously thought. Stroke may exist concomitantly with underlying Alzheimer''s disease (AD), and so we determined whether post-stroke memory dysfunction indicates manifestation of underlying subclinical AD.

Methods

Of 1201 patients in a prospective cognitive assessment database, we enrolled subjects with poststroke amnestic vascular cognitive impairment-no dementia (aVCIND; n=48), poststroke nonamnestic vascular cognitive impairment-no dementia (naVCIND; n=50), and nonstroke amnestic mild cognitive impairment (aMCI; n=65). All subjects had cognitive deficits, but did not meet the criteria for dementia. A standardized neuropsychological test battery and magnetic resonance imaging were performed at least 90 days after the index stroke (mean, 473 days). Visual assessment of medial temporal atrophy (MTA) was used as a measure of underlying AD pathology.

Results

The MTA score was significantly lower in the naVCIND group (0.64±0.85, mean±SD) than in the aVCIND (1.10±1.08) and aMCI (1.45±1.13; p<0.01) groups. Multivariable ordinal logistic regression analysis revealed that compared with naVCIND, aVCIND [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.21-5.99] and aMCI (OR=5.20; 95% CI=2.41-11.23) were significantly associated with increasing severity of MTA.

Conclusions

Our findings show that compared with poststroke naVCIND, the odds of having more-severe MTA were increased for poststroke aVCIND and nonstroke aMCI.     

Korean Version of Mini Mental Status Examination for Dementia Screening and Its' Short Form

Objective

We developed a Korean version of Mini-Mental Status Examination (MMSE) optimized for screening dementia (MMSE-DS) and its'' short form (SMMSE-DS).

Methods

We constructed the MMSE-DS using the items of the two current Korean versions of MMSE and then construct the SMMSE-DS consisted of 13 items from the MMSE-DS based on the diagnostic accuracy of individual items for dementia. We investigated reliability and validity of MMSE-DS and SMMSE-DS on 1,555 subjects (1,222 nondemented controls, 333 dementia patients). We compared the diagnostic accuracy of the SMMSE-DS with that of the three full Korean versions of MMSE, and examined its'' age- and education-specific optimal cutoff scores for dementia.

Results

The internal consistency obtained by Cronbach''s coefficient alpha was 0.826. The inter-rater reliability and test-retest reliability were 0.968 (p<0.001) and 0.825 (p<0.001), respectively. It showed significant correlation with the Clinical Dementia Rating (CDR) (r=-0.698, p<0.05) and the three full Korean versions of MMSE (r=0.839-0.938, p<0.001). The area under the receiver operator curve for dementia of the SMMSE-DS was larger than those of the three full Korean versions of MMSE (p<0.001). Age, education and gender explained 19.4% of the total variance of SMMSE-DS scores. The optimal cutoff scores for dementia of the SMMSE-DS were estimated differently by age and educational attainment of the subjects.

Conclusion

The SMMSE-DS was found to be accurate, brief and portable instrument for screening dementia in Korean elders, and may be particularly useful for screening dementia in elderly populations with wide variation in educational levels.     

Involvement of Peripheral and Central Nervous Systems in a Valosin-Containing Protein Mutation

Background

Inclusion-body myopathy with Paget''s disease of the bone and frontotemporal dementia (IBMPFD) is a rare, late-onset autosomal disorder arising from missense mutations in a gene coding for valosin-containing protein.

Case Report

We report the case of a man carrying the previously described p.Arg159His mutation, who had an unusual axonal sensorimotor neuropathy as the first clinical manifestation of IBMPFD, and for whom diagnosis only became clear 8 years later when the patient developed frontotemporal dementia.

Conclusions

Peripheral neuropathy is a rare manifestation of IBMPFD. This underdiagnosed disorder should be considered when a patient develops dementia or has signs of Paget''s disease.     

Altered Cell Viability and Proliferation Activity of Peripheral Lymphocytes in Patients with Alzheimer's Disease

Objective

We evaluated cell viability and proliferation activity of peripheral lymphocytes as potential models of neuronal death in Alzheimer''s disease (AD).

Methods

We analyzed the cell viability and proliferation activity of phytohemagglutinin (PHA)-activated lymphocytes from 68 AD patients and 33 normal controls. The cellular measures were made at baseline (0 hr), 24 hrs, 48 hrs, 72 hrs, and 96 hrs after PHA stimulation.

Results

Cell viability in the AD patients was significantly decreased at 72 hrs and 96 hrs, compared with the normal controls. The declining ramp of the proliferation activity from 48 hrs to 72 hrs after PHA stimulation was significantly related to cell viability at 72 hrs and at 96 hrs in the AD patients.

Conclusion

Lymphocytes from patients with AD have altered viability and proliferation characteristics in culture following PHA stimulation. These findings suggest that lymphocytes may be used as a peripheral tissue model of cell cycle dysregulation in AD.     

Multiplex Analysis of Cytokines in the Serum and Cerebrospinal Fluid of Patients With Alzheimer's Disease by Color-Coded Bead Technology

Background and purpose

The availability and promise of effective treatments for neurodegenerative disorders are increasing the importance of early diagnosis. Having molecular and biochemical markers of Alzheimer''s disease (AD) would complement clinical approaches, and further the goals of early and accurate diagnosis. Combining multiple biomarkers in evaluations significantly increases the sensitivity and specificity of the biochemical tests.

Methods

In this study, we used color-coded bead-based Luminex technology to test the potential of using chemokines and cytokines as biochemical markers of AD. We measured the levels of 22 chemokines and cytokines in the serum and cerebrospinal fluid (CSF) of 32 de novo patients (13 controls, 11 AD, and 8 Parkinson''s disease [PD]).

Results

MCP-1 was the only cytokine detectable in CSF, and its levels did not differ between control and disease groups. However, the serum concentration of eotaxin was significantly higher in AD patients than in the control group.

Conclusions

The analysis of multiple inflammatory mediators revealed marginal differences in their CSF and serum concentrations for the differential diagnosis of AD and PD. These results provide evidence that immunological responses are not major contributors to the pathogenesis of AD and PD.     

Hormones and dementia – a comparative study of hormonal impairment in post-menopausal women, with and without dementia

Context

Women seem to be more vulnerable to dementia, particularly Alzheimer’s disease (AD), than men. There is controversy among studies correlating estrogen deficit to cognitive impairment. Because of the sudden drop of estrogens in menopause, this hormonal deficit could represent one of the risk factors for the larger incidence and prevalence of AD in post-menopausal women.

Rationale

We therefore wanted to find out if post-menopausal women with dementia, or even in a prior stage, mild cognitive impairment (MCI), would have a more significant deficit of estrogens than post-menopausal women without dementia, or any other type of cognitive problem.

Objectives

The aim of this study was to detect possible differences of the sex hormone levels among post-menopausal women, simultaneously affected by MCI or dementia, in comparison with a control group without cognitive impairment.

Design, setting, and participants

A small, multicenter, prospective study was performed on 82 post-menopausal women (41 cases, 41 controls), aged 45–81 years, to investigate their sex hormone balance. The diagnosis of dementia was made according to ICD 9 or 10 and DSM III-R or IV appropriate to the time interval. The diagnosis of probable AD followed the NINCDS-ADRDA criteria. MCI met the Paquid-study criteria. Blood was analyzed in qualified centers for LH, FSH, and 17-β-estradiol. All women went through a thorough psychiatric examination and those with a suspected hormonal impairment were examined by a gynecologist.

Results

15 cases (36.6%) had impaired hormonal function, compared with 8 controls (19.5%). Of the 15 cases with hormonal impairment, 9 had MCI.

Conclusions

These preliminary data stress a considerable difference between the sex hormone status of these two populations, showing a tendency towards a more accentuated estrogen deficit linked to cognitive deficit. Enlarging the sample and following the evolution could bring more interesting data.     

Mild cognitive impairment: a systematic review

MCI is a nosological entity proposed as an intermediate state between normal aging and dementia. The syndrome can be divided into two broad subtypes: amnestic MCI (aMCI) characterized by reduced memory, and non-amnestic MCI (naMCI) in which other cognitive functions rather than memory are mostly impaired. aMCI seems to represent an early stage of AD, while the outcomes of the naMCI subtypes appear more heterogeneous--including vascular dementia, frontotemporal dementia or dementia with Lewy bodies--but this aspect is still under debate. MCI in fact represents a condition with multiple sources of heterogeneity, including clinical presentation, etiology, and prognosis. To improve classification and prognosis, there is a need for more sensitive instruments specifically developed for MCI as well as for more reliable methods to determine its progression or improvement. Current clinical criteria for MCI should be updated to include restriction in complex ADL; also the diagnostic and prognostic role of behavioral symptoms and motor dysfunctions should be better defined. A multidisciplinary diagnostic approach including biological and neuroimaging techniques may probably represent the best option to predict the conversion from MCI to dementia. In this review we discuss the most recent aspects related to the epidemiological, clinical, neuropathological, neuroimaging, biochemical and therapeutic aspects of MCI, with specific attention to possible markers of conversion to dementia.     

Factors Associated with Caregiver Burden in Patients with Alzheimer's Disease

Objective

Caregivers for patients with Alzheimer''s disease (AD) suffer from psychological and financial burdens. However, the results of the relationship between burden and cognitive function, performance of activities of daily living, and depressive symptoms have remained inconsistent. Therefore, the aim of this study was to examine which factors are more significant predictors of heightened burden, cognitive impairment or functional decline, besides neuropsychiatric symptoms.

Methods

A cross-sectional study was conducted in a sample comprised of 1,164 pairs of patients with AD and caregivers from the Clinical Research of Dementia of South Korea study cohorts. The cognitive function of each sub-domain, functional impairments, depressive symptoms, and caregiver burden were assessed using the dementia version of Seoul Neuropsychological Screening Battery (SNSB-D), Barthel Index for Daily Living Activities (ADL), Seoul-Instrumental Activities of Daily Living (S-IADL), the Clinical Dementia Rating Sum of Box (CDR-SB), the Global Deterioration Scale (GDS), the Korean version of the Neuropsychiatric Inventory (K-NPI), and the 15-item Geriatric Depression Scale.

Results

We found that higher severity (higher CDR-SB and GDS scores) and more functional impairment (lower ADL and higher S-IADL scores) were significantly associated with higher caregiver burden. In addition, depressive symptoms of patients (higher Geriatric Depression Scale scores) were associated with higher caregiver burden.

Conclusion

Therefore, interventions to help maintain activities of daily living in patients with AD may alleviate caregiver burden and improve caregiver well-being.     

Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe Atrophy, but with White Matter Changes in Alzheimer's Disease

Background and purpose

Elevated plasma total homocysteine (tHcy) levels are reported to be associated with an increased risk of Alzheimer''s disease (AD). However, the mechanism by which homocysteine contributes to the pathogenesis of AD is as yet unknown. The aim of this study was to elucidate the relationship between white matter changes (WMC) and medial temporal lobe atrophy (MTA) on brain magnetic resonance imaging (MRI), and plasma levels of tHcy in AD patients.

Methods

Seventy-two patients with a clinical diagnosis of probable AD were recruited to the study. Plasma tHcy levels, vascular risk factors, and WMC and MTA on brain MRI were evaluated in all patients. The AD patients were classified into two groups: those with no or minimal WMC (69.2±8.8 years, mean±SD, n=36) and those with moderate-to-severe WMC (74.6±4.6 years, n=36) on brain MRI.

Results

In a univariate logistic regression analysis, the risk of moderate-to-severe WMC in AD was significantly associated with increasing age, female gender, lower education level, hypertension, high plasma tHcy levels, and lower Mini-Mental State Examination (MMSE) score. Multivariate logistic regression analysis revealed only high plasma tHcy as the independent and significant risk factor for moderate-to-severe WMC [odds ratio (OR; adjusted for age, gender, education level, MMSE score, and hypertension comparing the top tertile - tHcy levels ≥12.9 µmol/L - with the bottom tertile - tHcy levels ≤9.4 µmol/L)=7.35; 95% confidence interval, confidence interval=1.36-39.84; p=0.02], and age as a borderline significant risk factor (OR=1.08, 95% CI=0.99-1.19, p=0.09) in AD patients. Plasma tHcy levels were not correlated significantly with either right or left MTA.

Conclusions

Our results suggest that the vascular pathway mediates the association between elevated plasma tHcy levels and AD.     

Pure Word Deafness in a Patient with Early-Onset Alzheimer's Disease: An Unusual Presentation

Background and Purpose

The occurrence of PWD in neurodegenerative disease is very rare, and this is the first report of it being related to early-onset AD. We describe a patient with early-onset Alzheimer''s disease (AD) who presented with pure word deafness (PWD).

Case Report

The patient had experienced PWD for 2 years, followed by other cognitive deficits suggestive of parietotemporal dysfunction. Brain imaging including ¹⁸FDG-PET and [¹¹C] PIB-PET supported the diagnosis of AD.

Conclusions

Our case highlights the clinical variability that characterizes early-onset AD.