Insight and cognitive impairment: effects on quality-of-life reports from mild cognitive impairment and Alzheimer's disease patients

This study follows previous work to determine the effect of patient insight and cognitive impairment on the reliability and validity of self-reported quality of life (QOL) from patients diagnosed with Alzheimer's disease (AD) and mild cognitive impairment (MCI). AD and MCI patients (N = 68) and their caregivers participated. Patients with impaired insight provided QOL ratings that were less reliable than those provided by patients with better insight. Patient-caregiver agreement for. QOL reports was used as an index of validity. Neither better insight nor lesser cognitive impairment suggested better agreement. Thus, even when patient insight is intact, patient reports are unlikely to agree with caregiver reports. Patient and caregiver reports about patient QOL may represent 2 unique, yet potentially valid, perspectives.     

Persistent mild cognitive impairment in geriatric depression

BACKGROUND: Cognitive impairment often occurs with geriatric depression and impairments may persist despite remission of depression. Although clinical definitions of mild cognitive impairment (MCI) have typically excluded depression, a neuropsychological model of MCI in depression has utility for identifying individuals whose cognitive impairments may persist or progress to dementia. METHODS: At baseline and 1-year follow-up, 67 geriatric patients with depression had a comprehensive clinical examination that included depression assessment and neuropsychological testing. We defined MCI by a neuropsychological algorithm and examined the odds of MCI classification at Year 1 for remitted depressed individuals with baseline MCI, and examined clinical, functional and genetic factors associated with MCI. RESULTS: Fifty-four percent of the sample had MCI at baseline. Odds of MCI classification at Year 1 were four times greater among patients with baseline MCI than those without. Instrumental activities of daily living were associated with MCI at Year 1, while age and APOE genotype was not. CONCLUSIONS: These results confirm previous observations that MCI is highly prevalent among older depressed adults and that cognitive impairment occurring during acute depression may persist after depression remits. Self-reported decline in functional activities may be a marker for persistent cognitive impairment, which suggests that assessments of both neuropsychological and functional status are important prognostic factors in the evaluation of geriatric depression.     

Separating mood disturbance from mild cognitive impairment in geriatric depression

Disentangling depression from dementia remains one of the most difficult clinical challenges for psychiatrists caring for older adults. The relationship between geriatric depression and dementia is complex for several reasons. First, cognitive impairment is often a prominent feature of depression in the elderly. Cognition may improve with successful treatment of depression but it may not normalize. Indeed, marked memory impairment in older depressed individuals may indicate a prodromal state of dementia. This review will examine issues related to depression and cognitive disorder in the elderly. The author will provide an evidence-based approach to separate mood disorder from cognitive disorder among older adults.     

Separating mood disturbance from mild cognitive impairment in geriatric depression

Disentangling depression from dementia remains one of the most difficult clinical challenges for psychiatrists caring for older adults. The relationship between geriatric depression and dementia is complex for several reasons. First, cognitive impairment is often a prominent feature of depression in the elderly. Cognition may improve with successful treatment of depression but it may not normalize. Indeed, marked memory impairment in older depressed individuals may indicate a prodromal state of dementia. This review will examine issues related to depression and cognitive disorder in the elderly. The author will provide an evidence-based approach to separate mood disorder from cognitive disorder among older adults.     

Perspectives on depression, mild cognitive impairment, and cognitive decline

CONTEXT: The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.     

Incidence and risk factors for mild cognitive impairment: a population-based three-year follow-up study of cognitively healthy elderly subjects

BACKGROUND: Mild cognitive impairment (MCI) has attracted considerable interest as a potential predictor of Alzheimer's disease (AD). Both the apolipoprotein E (ApoE) epsilon4 allele and vascular factors have been associated with a higher risk for AD, recently they have also been linked to the risk of MCI. OBJECTIVES: To estimate the incidence of MCI among cognitively healthy elderly subjects during a 3-year follow-up, and to evaluate the impact of demographic and vascular factors as well as the ApoE epsilon4 allele on the conversion to MCI. METHODS: At baseline, the cognitive abilities of 806 out of 1,150 eligible subjects (aged 60-76 years) from a population-based sample were examined. Cognitively intact subjects (n = 747) were followed for an average of 3 years. RESULTS: 66 subjects (8.8%) had converted to MCI. The global incidence rate of MCI was 25.94/1,000 person-years. Persons with higher age (OR 1.08, 95% CI 1.01-1.16), ApoE epsilon4 allele carriers (OR 2.04, 95% CI 1.15-3.64) and persons with medicated hypertension (OR 1.86, 95% CI 1.05-3.29) were more likely to convert to MCI than those individuals of lower age and without an ApoE epsilon4 allele or medicated hypertension. Persons with high education (OR 0.79, 95% CI 0.70-0.89) were less likely to convert to MCI than persons with low or no education. In subjects with both the ApoE epsilon4 allele and medicated hypertension, the crude OR for conversion was 3.92 (95% CI 1.81-8.49). In subjects with cardiovascular disease, the crude OR for conversion was 2.13 (95% CI 1.26-3.60). Gender, elevated blood pressure, diabetes or cerebrovascular disease had no significant effect on the conversion to MCI. CONCLUSION: Higher age, the presence of at least one ApoE epsilon4 allele and medicated hypertension are independent risk factors, but high education is a protective factor for MCI. The results suggest that vascular factors may have an important role in the pathogenesis of MCI.     

Free copper distinguishes mild cognitive impairment subjects from healthy elderly individuals

In patients affected by Alzheimer's disease (AD), serum copper not bound to ceruloplasmin ('free' copper) appears elevated, slightly but significantly enough to distinguish AD patients from healthy elderly subjects. In this paper we tested the hypothesis that this is also the case for individuals affected by mild cognitive impairment (MCI). A sample of 83 MCI subjects were compared with 100 elderly control subjects in terms of levels of serum copper, free copper, ceruloplasmin, apolipoprotein E4 genotype (APOE4), iron, transferrin, and total antioxidant capacity (TRAP). The groups were also compared in terms of demographic and cardiovascular risk factors. The comparison with an additional group of 105 mild to moderate AD patients was also evaluated. The possible effects of copper dysfunction on cognitive decline were evaluated by multinomial logistic regression analysis. A linear regression model was applied to define the role of metals and antioxidant dysfunction in explaining Mini-Mental Status Examination (MMSE) variations. APOE4 and free copper differentiated the MCI group from the healthy control group. The probability of acquiring MCI increased by about 24% for each free copper unit (μmol/L) increment. APOE4 and free copper differentiated the MCI group also from the AD group. APOE4 and free copper appeared associated to MMSE worsening, as did age and gender. These results suggest that free copper can help in discriminating MCI subjects from healthy controls, but not on an individual basis.     

Comparison of informant reports and neuropsychological assessment in mild cognitive impairment

The aim of this retrospective study was to investigate the accuracy of informant reports on cognitive status in mild cognitive impairment (MCI) by comparing the subjective evaluation made by patients' relatives with the objective results of neuropsychological assessment. We enrolled 119 MCI outpatients and their relatives. Cognitive impairment was assessed by a battery of standardized neuropsychological tests. Informant reports on cognitive functioning were obtained by means of a structured interview. Subjective and objective evaluations of cognitive status were rated according to the same scoring system in order to enable comparison. All but one relative reported cognitive dysfunctions at the interview, but the kind of cognitive profile emerging from their reports was quite different from the one highlighted by neuropsychological assessment. A subjective evaluation of cognitive status based on informant reports could therefore be useful to identify patients with MCI but is unable to define MCI subtypes.     

高频重复经颅磁刺激对老年抑郁症伴轻度认知功能损害患者的疗效

目的探讨高频重复经颅磁刺激（rTMs）对伴有轻度认知功能损害的老年抑郁症患者的疗效。方法将48例伴有轻度认知损害的老年抑郁症患者随机分为对照组和试验组。对试验组患者进行为期4周、频率为20Hz的rTMS治疗。在治疗前、治疗后和治疗后3个月分别进行汉密尔顿抑郁量表（HAMD）、简易精神状态量表（MMSE）,事件相关电位P300测试。结果治疗后,试验组HAMD评分低于对照组（t=-3．711,P=0．001）,3个月后差异仍有统计学意义（t=-3．978,P〈0．01）。治疗后,试验组的MMSE评分高于对照组（t=2．705,P=0．010）,3个月后差异仍有统计学意义t=2．934,P=0．006）。治疗后和治疗3个月后,和对照组相比,试验组Fz和Cz的P300波幅较大,差异有统计学意义（P〈0．01）。治疗后和治疗3个月后,试验组Fz和Cz的P300潜伏期短于对照组,差异均有统计学意义（P〈0．05）。结论rTMS治疗可同时改善伴轻度认知损害老年抑郁症患者的抑郁情绪和认知功能。     

Differential cortical atrophy in subgroups of mild cognitive impairment

OBJECTIVE: To compare gray matter brain volumes in patients diagnosed with subtypes of mild cognitive impairment (MCI) (those with a focal amnestic disorder and those with more diffuse cognitive dysfunction) with those of elderly controls. DESIGN: Magnetic resonance imaging volumetric study of MCI subgroups (MCI-amnestic [MCI-A], and MCI-multiple cognitive domain [MCI-MCD]) using a whole brain voxel-based analysis. SETTING: Referral dementia clinic.Patients Thirty-seven patients with MCI (age range, 49-85 years; MCI-A, n = 9; MCI-MCD, n = 28) and 47 control subjects (age range, 55-81 years). MAIN OUTCOME MEASURES: Volumetric anatomical magnetic resonance imaging differences between MCI subgroups and normal controls, and between patients with MCI who progressed to dementia. Magnetic resonance imaging scans were analyzed using statistical software SPM99. RESULTS: Overall, the patients with MCI had significantly decreased volume in the hippocampus and middle temporal gyrus, bilaterally, compared with control subjects. Compared with patients with MCI-MCD, patients with MCI-A had significant volume loss of the left entorhinal cortex and inferior parietal lobe. Compared with patients with MCI-A, patients with MCI-MCD had significantly reduced volume of the right inferior frontal gyrus, right middle temporal gyrus, and bilateral superior temporal gyrus. Patients with MCI who progressed to Alzheimer disease during follow-up (mean interval 2 years, maximum 4.5 years), showed greater atrophy in the left entorhinal cortex, bilateral superior temporal gyri, and right inferior frontal gyrus compared with those who did not progress. CONCLUSIONS: These data provide evidence of distinct brain structural abnormalities in 2 groups of patients with MCI. While both have mesial temporal and cortical volume loss, those with a focal memory deficit have more involvement of the mesial temporal structures and less involvement of the neocortical heteromodal association areas than those patients with MCI with diffuse cognitive dysfunction. Thus, MCI may represent a more heterogeneous group than currently conceived, possibly reflecting 2 different etiological processes to dementia. These data also suggest that these structural abnormalities precede the development of Alzheimer disease.     

老年人轻度认知功能损害的神经心理测验研究

目的;用神经心理测验研究老年人轻度认知功能损害的特点。方法;为横断面比较研究。研究对象分为两组,即有轻度认知功能损害的老年人（ＭＣＩ组）和认知功能正常的老年人（对照组,ＮＣ组）。以世界卫生组织老年认知功能介成套神经心理测验（ＷＨＯ－ＢＣＡＩ）为主要研究工具。     

Cholinotrophic molecular substrates of mild cognitive impairment in the elderly

Cholinergic nucleus basalis (NB) neurons provide the major cholinergic innervation to the cortical mantle, are selectively vulnerable in late stage Alzheimer's disease (AD) and require the neurotrophin, nerve growth factor (NGF) and its receptors (TrkA and p75(NTR)), for their survival. The molecular events underlying the demise of these neurons in AD were investigated using tissue harvested from participants in a longitudinal clinical pathological study of aging and AD who agreed to an annual clinical evaluation providing a categorization of no cognitive impairment (NCI), mild cognitive impairment (MCI) or AD and postmortem brain donation. Although the number of choline acetyltransferase (ChAT)-positive neurons was unchanged, TrkA and p75(NTR) receptor-containing neurons, which co-localize with ChAT, were significantly reduced in the NB of subjects with MCI and AD compared to those with NCI. These observations indicate a phenotypic down-regulation rather than frank NB neuronal degeneration in MCI. Expression profiling of single cholinergic NB neurons revealed TrkA but not p75(NTR) mRNA is reduced in MCI, suggesting that decreased neurotrophin responsiveness may be an early biomarker for AD. The NGF precursor molecule, proNGF, is increased in the cortex in MCI and AD. Since proNGF accumulates in the presence of reduced cortical TrkA and sustained levels of p75(NTR), a shift in the balance between cell survival and death molecules may occur in prodromal AD. Coincident with these phenomena, brain derived neurotrophic factor (BDNF) and its precursor molecule, proBDNF, are reduced in the MCI cortex, potentially depriving CBF neurons of additional trophic factor support. Moreover, there is a shift in the ratio of 3 repeat tau to 4 repeat tau gene expression, whereas total tau message is stable in NB neurons during the disease process. These data suggest there is a shift in cholinotrophic molecular events in MCI and early AD which may lead to cell dysfunction and eventual cell death over the course of the disease. These findings support the concept that from a neurotrophic pathobiologic perspective, MCI is already early AD.     

Sertraline treatment of elderly patients with depression and cognitive impairment

BACKGROUND: There is little information on the efficacy and side effects of antidepressant treatment in elderly patients with combined depression and cognitive impairment without dementia (DEP-MCI), and it is unclear if cognitive performance improves with antidepressant response in these patients. METHODS: In 39 elderly DEP-MCI patients, changes in depression and cognitive impairment were evaluated with open sertraline treatment up to 200 mg/day for 12 weeks. RESULTS: Of the 26 completers, 17 were responders and nine were non-responders. Diagnostic subtype of depression was unrelated to response. ANCOVA on WAIS-R digit symbol percent change scores revealed a significant effect for responder status (F = 5.59, p < 0.03), and age (F = 0.24, p < 0.64) and education (F = 1.64, p < 0.22) were not significant covariates. From pre-trial to post-trial, responders improved in WAIS-R digit symbol percent change scores (Mean -10% SD 24) while non-responders declined (Mean 14% SD 18; t = 2.60, p < 0.02). Other neuropsychological measures were unrelated to response. Percent change in HRSD scores showed significant inverse correlations with percent change in several cognitive measures. CONCLUSIONS: DEP-MCI patients showed moderate clinical response to sertraline treatment. When responders were compared to non-responders, cognitive improvement was limited to one measure of attention and executive function. Overall, there was little cognitive improvement with antidepressant treatment. The findings indirectly suggest that lack of improvement in cognition following treatment of depression in DEP-MCI patients may be associated with increased risk of meeting diagnostic criteria for dementia during follow-up.     

Association between tea consumption and cognitive function in cognitively healthy older adults and older adults with mild cognitive impairment

BackgroundProspective studies suggest that tea consumption may decrease the risk for cognitive impairment in late life. However, little research has examined the association between tea consumption and cognitive performance across multiple domains. In addition, no research has examined the benefit of tea consumption on cognitive performance among older adults with existing impairment.AimsThe current study examined the association between tea consumption and performance on tasks of global cognitive function, episodic memory and executive function in cognitively healthy (CH) older adults and older adults with mild cognitive impairment (MCI).MethodsThe analytical sample included 1849 community-dwelling older adults from the Shanghai Brain Aging Study (65.6% female, mean age of 69.50 (8.02) years). Following ascertainment of cognitive function, 816 were categorised as MCI. In addition to completion of a demographics questionnaire, participants reported their tea consumption and completed a battery of tests to measure global cognitive function, episodic memory and working memory.ResultsIndependent analyses of covariance revealed a significant association between tea consumption and measures of episodic memory; however, these associations were restricted to CH older adults but not older adults with MCI. Tea consumption was not associated with working memory performance.ConclusionsThe current study suggests that the benefit of tea consumption is restricted to cognitively healthy older adults and does not extend to older adults with MCI.