18FTHK5351 PET Imaging in Patients with Mild Cognitive Impairment

Background@#and PurposeMild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [18F]THK5351 in MCI subgroups. @*Methods@#This study included 96 participants comprising 38 with amnestic MCI (aMCI), 21 with nonamnestic MCI (naMCI), and 37 with normal cognition (NC) who underwent 3.0-T MRI, [18F]THK5351 PET, and detailed neuropsychological tests. [18F]flutemetamol PET was also performed in 62 participants. The aMCI patients were further divided into three groups: 1) verbal-aMCI, only verbal memory impairment; 2) visual-aMCI, only visual memory impairment; and 3) both-aMCI, both visual and verbal memory impairment. Voxel-wise statistical analysis and region-of-interest -based analyses were performed to evaluate the retention of [18F]THK5351 in the MCI subgroups. Subgroup analysis of amyloid-positive and -negative MCI patients was also performed. Correlations between [18F]THK5351 retention and different neuropsychological tests were evaluated using statistical parametric mapping analyses. @*Results@#[18F]THK5351 retention in the lateral temporal, mesial temporal, parietal, frontal, posterior cingulate cortices and precuneus was significantly greater in aMCI patients than in NC subjects, whereas it did not differ significantly between naMCI and NC participants. [18F] THK5351 retention was greater in the both-aMCI group than in the verbal-aMCI and visualaMCI groups, and greater in amyloid-positive than amyloid-negative MCI patients. The cognitive function scores were significantly correlated with cortical [18F]THK5351 retention. @*Conclusions@#[18F]THK5351 PET might be useful for identifying distinct topographic patterns of [18F]THK5351 retention in subgroups of MCI patients who are at greater risk of the progression to Alzheimer's dementia.

Efficacy of Cognitive Health Promotion Workbook for Community-Dwelling Elderlies with Mild Cognitive Impairment or Dementia Performed by Trained Dementia Partners

OBJECTIVE: The aim of this study is to assess the efficacy of cognitive health promotion workbook for community-dwelling elderlies with mild cognitive impairment and dementia performed by trained dementia partners. METHODS: The trained dementia partners performed cognitive training program with the workbook developed by Incheon Metropolitan Dementia Center to 36 participants with mild cognitive impairment or dementia at their home. The cognitive training program consisted of 60-minute sessions held twice weekly for 10 weeks. We evaluated their cognitive performances at baseline and after intervention. Pre- and post-intervention measures included Korean version of Mini-Mental Status Examination for Dementia Screening (MMSE-DS), Global Deterioration Scale, Korea Activities of Daily Living Scale, Korea Instrumental Activities of Daily Living Scale, Korean Version of Short Form Geriatric Depression Scale (SGDS-K) and Korean Quality of Life-Alzheimer's Disease (KQoL-AD). RESULTS: Participants showed significant improvements compared with their baseline in MMSE-DS (p=0.002), SGDS-K (p=0.001) and KQoL-AD (p<0.001). There were no significant differences of improvement between high cognitive function group (MMSE ≤20, n=16) and low cognitive function group (MMSE ≤20, n=20). CONCLUSION: These findings suggest that the cognitive training program with cognitive health promotion workbook can improve cognitive function, quality of life and depression for community-dwelling elderlies with mild cognitive impairment and dementia and it would be efficient that trained dementia partners perform the cognitive training program regularly at their home.

¹⁸F-THK5351 PET Imaging in the Behavioral Variant of Frontotemporal Dementia

BACKGROUND AND PURPOSE: Behavioral variant frontotemporal dementia (bvFTD) is a subtype of frontotemporal dementia, which has clinical symptoms of progressive personality and behavioral changes with deterioration of social cognition and executive functions. The pathology of bvFTD is known to be tauopathy or TDP-43 equally. We analyzed the 18F-THK5351 positron emission tomography (PET) scans, which were recently developed tau PET, in patients with clinically-diagnosed bvFTD. METHODS: Forty-eight participants, including participants with behavioral variant frontotemporal dementia (bvFTD, n=3), Alzheimer's disease (AD, n=21) and normal cognition (NC, n=24) who completed 3T magnetic resonance images, 18F-THK5351 PET scans, and detailed neuropsychological tests were included in the study. Voxel-wise statistical analysis and region of interest (ROI)-based analyses were performed to evaluate the retention of THK in bvFTD patients. RESULTS: In the voxel-based and ROI-based analyses, patients with bvFTD showed greater THK retention in the prefrontal, medial frontal, orbitofrontal, anterior cingulate, insula, anterior inferior temporal and striatum regions compared to NC participants. Left-right asymmetry was noted in the bvFTD patients. A patient with extrapyramidal symptoms showed much greater THK retention in the brainstem. CONCLUSIONS: The distribution of THK retention in the bvFTD patients was mainly in the frontal, insula, anterior temporal, and striatum regions which are known to be the brain regions corresponding to the clinical symptoms of bvFTD. Our study suggests that 18F-THK5351 PET imaging could be a supportive tool for diagnosis of bvFTD.

Dementia Care by Healthy Elderly Caregivers Is Associated with Improvement of Patients' Memory and the Caregivers' Quality of Life: A Before and After Study

OBJECTIVE: The provision of care for elderly people with dementia by healthy elderly caregivers is one of the new health-care paradigms in South Korea. The aim of this study was to determine whether this type of care, which includes cognitive stimulation, would improve the cognitive function of dementia patients and the quality of life of the healthy elderly caregiver. METHODS: Totals of 132 dementia patients and 197 healthy elderly caregivers participated in this study. We evaluated the cognitive function of the dementia patients at baseline and after providing the program for 6 months using the Korean version of the Consortium to Establish a Registry for Alzheimer's disease, 1st Edition (CERAD-K). We also evaluated the quality of life of the healthy elderly caregivers using the World Health Organization Quality of Life-Short Version (WHOQOL-BREF) at baseline and after 6 months. RESULTS: The word-list memory results of CERAD-K for the included dementia patients improved after 6 months (Z=-2.855, p=0.004). The WHOQOL-BREF score among the elderly caregiver also improved significantly (Z=-2.354, p=0.019). CONCLUSION: These data suggest that dementia care is associated with improvements in both the cognitive function of dementia patients and the quality of life of the healthy elderly caregivers.

Comparative Study of the Effects of Supportive Educational Programs : for Family Caregivers of the Elderly with Dementia

OBJECTIVE: We studied the effect of Hyu-Sig-Gong-Gan and Hye-Ah-Rim on several evaluations and compared the two programs. We then investigated factors associated with the difference between pre- and post-ratings. METHODS: Thirty-six patients were randomized to Hyu-Sig-Gong-Gan (n=23) or Hye-Ah-Rim (n=13). We tested for the effect of each program on several evaluations and compared the two programs through Zarit Burden Interview (ZBI), Center for Epidemiologic Studies-Depression Scale, Dementia Attitude Scale (DAS)-intelligence, DAS-comfort and DAS-total. We then investigated whether the difference between pre- and post-rating depends on other factors. RESULTS: We observed significant positive effect of Hyu-Sig-Gong-Gan on DAS-comfort (t=1.843, p=0.039) and significant positive effect of Hye-Ah-Rim on ZBI (t=-2.327, p=0.019), DAS-comfort (t=2.241, p=0.022), and EuroQol-5 Dimensions-Visual Analogue Scale (t=2.537, p=0.013). For comparing the two programs, we found a lack of evidence for the difference in any of the five commonly observed evaluations. In the secondary analysis, we observed a strong trend that the two programs were particularly effective for caregivers with negative pre-ratings. CONCLUSION: The two programs showed positive effects on the various evaluations, but some evaluations could not reach statistical significance. The programs appear to be particularly helpful for those who are in need before the program participation.

Non-Adherence to Psychiatric Intervention in Work Related Burns

PURPOSE: Patients with work related burns suffer from anxiety, depression, insomnia and suicide ideation etc. Psychiatric symptoms could be reduced by treatment. Almost all patients are referred to psychiatric intervention in our hospital. However, a number of patients show non-adherence. The aim of this study is to figure out the reason of non-adherence and psychiatric symptoms of work related burns patients. METHODS: 123 patients participated in this study. Startle, Physiological arousal, Anger, and Numbness (SPAN), Feeling Suicide, Patient Health Questionnaire-2 (PHQ-2) were administered as screening tool. Questions about psychiatric intervention and reasons to refuse psychiatric intervention were asked. RESULTS: 32% patients were depressed, 34% patients had suicide ideation and 59% had PTSD after work related burns. However, 46% of burn patients had not been treated. Stigma of psychiatric intervention and concerns about dependency were major reasons for non-adherence. CONCLUSION: There are gap between necessity and reality of psychiatric intervention on work related burn patients.

Current Diagnostic Criteria of Alzheimer's Disease

As Alzheimer's disease is the most common cause of dementia in older people, many efforts for accurate and reliable clinical diagnoses have been made all over the world. Generally diagnostic process of Alzheimer's disease is constituted with two steps : 1) to determine whether a patient is actually demented, 2) to determine whether the dementia actually caused by Alzheimer's disease. Newly developed diagnostic criteria, such as diagnostic criteria of the National Institute on Aging-Alzheimer's Association improve their specificity to diagnose Alzheimer's disease. We need Korean specific guideline for diagnosing Alzheimer's disease compatible in Korean clinical situation.

Clinical practice guideline for dementia by Clinical Research Center for Dementia of South Korea

The Clinical Research Center for Dementia of South Korea (CREDOS), a nation-wide clinical dementia research group, has prepared clinical practice guidelines (CPG) for dementia tailored to the Korean population. In this article, a summary of the CREDOS CPG is presented with the Korean and English version of full report included in the appendix. The CREDOS CPG in intended not only for psychiatrists and neurologists, but also internists, family physicians, and other primary care physicians involved in the prevention and early diagnosis of dementia. While our CPG for dementia mainly covers Alzheimer's disease (AD) and vascular dementia (VaD), it also includes mild cognitive impairment (MCI) and vascular MCI, which are currently known to be the preclinical stages of AD or VaD, respectively, with emphasis placed on early diagnosis. The CREDOS CPG aims to achieve the following goals by developing CPG for dementia: to establish evidence-based, objective and clear clinical standards for dementia; to improve the clinical decision-making process for patients with dementia; to provide scientific and systematic scales to aid in the work of dementia specialists; to suggest comprehensive and systematic healthcare services tailored to each dementia subtype. The CREDOS CPG focuses on diagnosis and evaluation of clinical practice available domestically, and provides useful concepts of dementia. Its emphasis is on etiologies and epidemiology, diagnostic criteria and evaluation, neuropsychological tests, behavioral and psychological symptoms, the activities of daily living, laboratory tests, and brain imaging.

A Study on the Communication Gap and Different Understandings between Doctor and Patient about Burn Treatment in the Burn Center of a University Hospital

PURPOSE: Burn is an unusual medical situation with limited information open to common people. This study was designed to evaluate the communication gap and different understandings between doctor and patient about burn treatment and to improve quality of the treatment. METHODS: Cross-sectional studies were done with interview and questionnaire. 25 doctors and nurses of burn ward and 50 burn patients in Han-gang Sacred Heart Hospital Burn Center were participated. To understand the communication gap and different perception between doctors' and patients' on 1) burn sequela and recovery, 2) disease course and prognosis, 3) healing environment, cost, hospitalization, 4) nurse-physician collaboration, 5) psychiatric consultation, 6) extra incentive were analyzed. RESULTS: Patients tend to expectation positive answer about their prognosis from their physician but they have recognized chronic and negative prognosis of burn treatment. Patients want to know clear and detailed explanation about their test result or treatment methods. Physicians thought that it is important to consider patients' economic status and provide different treatment principle. Short duration of hospitalization is not related to the anxiety of rehabilitation. Patients thought that nurses could manage superficial or repeated treatment. It is more likely that physicians warn the disadvantages of psychiatric consultation than patients. Both groups thought that extra incentive or gratitude money is not helpful for the doctor patient relationship. CONCLUSION: Given the discrepant views of physicians and patients on the burn treatment, physician should be aware of the discrepancies and attempts to resolve any differences.

Pathways Analysis for Depression in Hospitalized Acute Burn Patients

PURPOSE: The goal of this study was to develop a model of risk factors for depression in hospitalized burned patients. METHODS: Seventy-seven patients over 20 tears of age who were admitted to the Hangang Sacred Heart Hospital for burn injury, completed Structured Interview Post-traumatic stress disorder (PTSD), Beck Depression Inventory (BDI), Visual Analogue Scale (VAS) for pain and itching after 1 month from burn. A path analytic strategy was used to develop a model of risk factors for depression in burned patients. RESULTS: Two pathways to depression were developed. 1) From sleep disturbance and then to depression 2) from burn pain to PTSD and then to depression. It was revealed that sleep disturbance and PTSD had a direct effect on depression, pain had both direct and indirect effect on depression. CONCLUSION: Sleep disturbance and PTSD are associated with depression in burned patients. The identification of two developmental pathways suggests the importance of establishing preventive interventions for depression.

A Validation Study of the Korean -Version of the Montgomery- Asberg Depression Rating Scale / 신경정신의학

OBJECTIVES: The Montgomery-Asberg Depression Rating Scale (MADRS) has been reported as a valid tool for the assessment of depression because it is based on the core symptoms of depression. The aim of this study is to assess the reliability, validity and psychometric properties of the Korean version of the MADRS (K-MADRS). METHODS: One hundred seven patients, including in-patients and out-patients, diagnosed as major depressive disorder according to the DSM-IV criteria were enrolled in this study. They were assessed with K-MADRS, Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI) and Clinical Global Impression (CGI) to examine cross-validation. Statistical analysis was done using calculation of Cronbach's alpha, Spearman Correlation Coefficient and Principal Components Analysis. RESULTS: The Cronbach's alpha coefficient of K-MADRS was 0.79. And the correlations of each item with total score were statistically significant (r=0.47-0.75, p<0.001). The inter-rater reliabilities of total score (r=0.89, p<0.001) and individual score (r=0.74-0.95, p=0.001) were high. The factor analysis revealed two factors. However, the first one accounted for 39% of variance, while the second one only for 11.1%. The total score of K-MADRS showed a significant correlation with those of HDRS, BDI and CGI (r=0.82, 0.47, 0.74, respectively, p=0.001). CONCLUSION: The K-MADRS showed good reliability and validity for the assessment of severity of depressive symptoms. And it demonstrated similar psychometric properties to previous studies. The K-MADRS is an useful instrument for assessing depressive symptoms in Korea.

A Community Study of Depression in Old Age

BACKGROUNDS: Depression in old age has significant negative impact on physical health and social activities, which may greatly burden a society with increased costs of use of health care resources and may seriously hamper individual's quality of life. This study aimed to identify the prevalence and risk factors of depression in older community population. METHOD: By the random sampling, study population(n=1,300) was selected out of total population of the elderly aged 65 years or older in Asan city(N=14,977). Two-phase community survey method was used; the Korean version of the Geriatric Mental State Schedule(GMS-K) was used as a screening instrument to define caseness group by trained interviewers, while board-certified psychiatrists confirmed clinical diagnoses according to the DSM-IV criteria by face-to-face interview of subjects for the Stage 2 study. RESULTS: Of 1,300 subjects, 1,246 elderly completed the stage 1 screening interview(=95.9%). Prevalence of all depressive disorders were 10.5%(male 7.4%, female 12.8%); 8.7% in major depression(male 6.3%, female 10.6%), 0.5% in dysthymic disorder(male 0.4%, female 0.6%), and depressive disorder NOS 0.5%(male 0.2%, female 0.7%). A high risk of depressive disorder was found among elderly women(OR= 1.54, 95% CI 1.08-2.20) and among those with physical illnesses(OR=1.82, 95% CI 1.33-2.48), especially those with vascular risk factors(OR=1.96, 95% CI 1.43-2.69). CONCLUSION: The association between physical health and depression in old age is a consistent finding across world. Systemic efforts to reduce incidence of depression and especially to prevent and treat vascular risk factors may be able to improve mental health in the elderly.

The Validity of the Assessment Tools for the Korean Long-Term Care System

OBJECTIVES: For the further development of the Korean Long-Term Care System, we analyzed the validity of the assessment tools of cognitive impairment and behavioral problems for the Korean Long-Term Care System. METHODS: We investigated 326 elderly people who were residing in Onyang 4-dong and Dogo-myun, Asan-si, Chungcheongnamdo. Our research team visited their residence and performed the assessment tools for the Korean Long-Term Care System and Korean version of the Mini-Mental State Examination (MMSE-K), Neuropsychiatric Inventory-Questionnaire (NPI-Q) and Seoul-Instrumental Activities of Daily Living (S-IADL). RESULTS: The correlation between the cognitive function tests and MMSE-K (r=0.579, p<0.001) and that between the behavioral problem tests and NPI-Q (r=0.688, p<0.001) were not as good as we expected. Moreover, if the items of the behavioral problem tests were decreased to 10 items as the government wanted, we got much lower correlation coefficiency. The cognitive function tests could not detect early cognitive deterioration in dementia. CONCLUSION: The assessment tools of cognitive impairment and behavioral problems for the Korean Long-Term Care System need modifications to promote validity.

Clinical Features of Elderly Patients Referred to Neuropsychiatric Department

OBJECTIVE: As the geriatric admission and geropsychiatric consultation increase, more study was needed about geropsychiatric consultation. This comparative study investigates the character of geropsychiatric consultation in general hospital. METHOD: We compared 22 young patients (25(age<45) with 55 elderly patients ((65) who are consulted to neuropsychiatry department for the first time for 3 months (2004. 1. 1-2004. 3. 31) in Kang-Dong Sacred Heart Hospital, Hallym University. Data on patterns of consultation, demography, psychiatric and physical illness were collected and analyzed. RESULT: 1) The rate of psychiatric consultations for elderly patients was 6.2%, and this rate was much higher than 1.9% of young patients. 2) There were no significant difference in referral department between the elderly group and the control group, and internal medicine was the most common referral department in both groups. 3) The main reasons of consultations were alcohol related problems and psychiatric follow up in order in control group, but sleep disturbance and disorientation in order in elderly group. 4) In elderly group, the most frequent psychiatric diagnoses made by consultants were organic brain disorder such as dementia and delirium, but in control group, they were functional psychiatric disorder such as alcohol related disorder and psychosis. 5) Psychotropic drug and follow-up consultation were two most frequent recommendations from consultants in both group. But recommendations for psychotherapy and psychosocial management were rare in both groups. 6) There were significant difference only in psychiatric transfer among compliance for psychiatric consultation between the elderly group and the control group. Compliance for recommendations were low in both groups. 7) In both group, only one follow up consultation was done. And OPD follow up after discharge was rare in both groups. CONCLUSION: Elderly patients need more psychiatric consultations than younger patients and has different characteristics in pattern of consultations. Further studies are warranted on geropsychiatric consultation in Korea.

Assessment and Judgement of Long Term Care System of Elderly

No abstract available.

The Efficacy and Safety of Milnacipran in Patients with Major Depression: A comparison with Fluoxetine / 신경정신의학

OBJECTIVES: This 6-week, open label randomized, multicenter study was conducted to evaluate the antidepressant effect and safety of milnacipran and fluoxetine in patients with major depression. METHODS: The study was done in patients with major depression diagnosed by DSM-IV who score > or =17 in 17 items Hamilton Rating Scale for Depression (17-item HAM-D) and score > or =25 in Montgomery and Asberg Depression Rating Scale (MADRS). A total of 87 patients were randomized to milnacipran group and fluoxetine group. In cases of the patients taking other antidepressants, 6 weeks of each medication was administered after 7 days of drug excretion period. The evaluation was done using 17 item HAM-D, MADRS, Clinical Global Impression Scale (CGI), and COVI scale after baseline, 1 week, 2 weeks, 4 weeks, and 6 weeks. The side effects that had occurred during the period of our study were put in records by developed/disappeared time, severities, incidences, managements and results. RESULTS: A total of 87 patients were enrolled. 70 (milnacipran group 39;fluoxetine group 31) of them were included for the 6 weeks of research and 17 of them dropped out within the first week, not due to adverse reactions or deficiency of effects. Total 17 item HAM-D scores, total points of MADRS, and CGI showed significant decrease after 1 week in each treatment group and continued decrease after 2 weeks and 4, 6 weeks. But there was no difference between milnacipran group and fluoxetine group in the antidepressant effect. There were no significant changes in vital sign, CBC, chemistry, and EKG in each treatment group. The commonly reported side effects of minlacipran were nausea (25.0%), headache (10.7%), vomiting (7.1%), constipation (7.1%), dizziness (7.1%) and those of fluoxetine were GI trouble (11.1%), diarrhea (11.1%), insomnia (11.1%), agitation (5.6%), and dizziness (5.6%). CONCLUSION: Milnacipran was effective for the improvement of depressive symptoms and was well tolerated and safe in patients with depression.

Practice Guidelines for the Manegement of Alzheimer's Disease

No abstract available.

Development and Standardization of the Computerized Memory Assessment for Korean Adults / 신경정신의학

OBJECTIVE: This study was conducted to develop the computerized memory tests for Korea adults. It also aimed at evaluating the reliability and validity of these tests and providing their normative data. METHODS: Computerized versions of digit span, visual span, auditory verbal learning test, and visual learning test were developed through several steps of preliminary applications and corrections. The test-retest reliabilites of each test was evaluated by the paired t-test and Pearson's correlation coefficient using the data from 27 normal persons. The validity of each test was evaluated by the Pearsons's correlation coefficient between the computerized test scores and the pre-existing cognitive function tests using the data from 48 normal persons. The normative data were obtained from the 150 Korean adults, age 20 to 50, whose educational levels were higher than high school graduate. RESULTS: There were no statistical differences between the means of the test and retest scores. High correlations were also observed between the tests and the retest scores (r ranged from 0.405 to 0.873). The computerized digit span, visual span, and auditory verbal learning tests scores were highly correlated with the pre-existing memory measures. The computerized memory test scores were greatly influenced by the educational level. The visual learning test seems useful, however, it requires methodological refinement. The normative data and guidelines for interpretation were provided. CONCLUSIONS: Clinically applicable computerized memory assessment tools with high reliability and validity were developed. The normative data for the Korean adults aged 20 to 50 were obtained and the guidelines for the interpretation were provided.

Reliability and Validity of the Korean Version of GMS-AGECAT / 신경정신의학

OBJECTIVES: This study aims to confirm the reliability and validity of the GMS-AGECAT(Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy in a Korean elderly population. METHODS: Translation committee developed Korean version GMS translating GMS-A3 after preliminary studies. Few changes from the original English version were necessary. A random sample(N= 1256 of the elderly(65+ years in Asan, community was assessed for diagnostic validity. A two-phase study was designed: Korean version of GMS-AGECAT, MMSE and GDS rated by lay interviewer and clinical assessment by psychiatrists according to DSM-IV. A consecutive hospital sample(N=28 of the elderly(65+ years admitted in Hangang Sacred Heart Hospital was assessed for reliability, concurrent & procedural validity. RESULTS: Reliability coefficients of GMS-AGECAT diagnosis were Inter-rater kappa 0.78 and test-retest kappa 0.56. Correlation coefficients for concurrent validity were 0.76 with MMSE and 0.73 with GDS. Procedural validity of psychiatrist's GMS-AGECAT diagnosis and lay-interviewers' were as follow: case/ no case distinction sensitivity 95.5%, specificity 75%; organicity distinction sensitivity 100%, specificity 83.3% and depression distinction, sensitivity 92.3%, specificity 100%. Diagnostic validity of DSM-IV diagnoses and GMS-AGECAT diagnoses were: case/ no case distinction sensitivity 92.7%, specificity 81%, dementia distinction sensitivity 77.3%, specificity 92.1% and depression distinction sensitivity 83.6%, specificity 84.1%. CONCLUSIONS: This study confirms the reliability and validity of the GMS-AGECAT in Korean elderly. Korean version GMS can be used in the international comparison studies.

Epidemiology of Age-Associated Memory Impairment

It has been widely known that the elderly suffer very mild cognitive impairment including memory function that cannot satisfy the criteria of dementia. Koivisti and Hannien et al reported that the prevalences of age-associated memory impairment and age-associated cognitive decline were 38.6% and 26.6%, respectively. The prevalence rate of male was more than that of female and the prevalence rate was increased in younger elderly. The risk factors of age-related cognitive decline were age and myocardiac infarction whereas education and smoking decreased the risk of age-related cognitive decline. The small portion of age-associated memory impairment progressed toward dementia but the most of them were nonprogressive. The probability of progression toward dementia could be predicted by detailed neurocognitive function test. The further epidemiologic studies will reveal the nature of age-associated memory impairment.