The power of personality in discriminating between healthy aging and early-stage Alzheimer's disease

This study examined differences in personality in the earliest stages of dementia of the Alzheimer type (DAT) relative to healthy aging, and the power of personality in discriminating healthy aging from early-stage DAT. Four groups of participants (middle-aged controls, older controls, persons with very mild DAT, and persons with mild DAT) and their families were administered Costa and McCrae's NEO Five-Factor Inventory. On the basis of both self-report and informant report, there was an increase in neuroticism and a decrease in conscientiousness in persons with very mild DAT relative to healthy individuals without it, and in persons with mild DAT relative to those with very mild DAT. Moreover, informant reports of neuroticism and conscientiousness capture substantial unique variance in discriminating healthy aging and very mild DAT, above and beyond standard neuropsychological tests. Discussion focuses on the importance of personality traits as a noncognitive indicator of early-stage DAT.     

Longitudinal driving performance in early-stage dementia of the Alzheimer type

OBJECTIVES: To longitudinally assess on-road driving performance in healthy older adults and those with early-stage dementia of the Alzheimer type (DAT). DESIGN: A prospective longitudinal study. SETTING: Large urban medical center and surrounding area. PARTICIPANTS: A sample of 58 healthy controls, 21 participants with very mild DAT, and 29 participants with mild DAT participated. DAT was diagnosed using validated clinical diagnostic criteria and staged according to the Clinical Dementia Rating (CDR) Scale. MEASUREMENTS: Healthy controls and individuals with very mild DAT and mild DAT were administered a standardized on-road driving assessment over repeated times of testing. RESULTS: Subjects in the CDR=1 group (mild DAT) had a faster rate of receiving a rating of not safe on the driving test than subjects in the CDR=0 group (healthy controls; log rank test, P=.006), and the survival function of the CDR=0.5 group (very mild DAT) fell between those of the CDR=0 and CDR=1 groups. A Cox proportional hazards model indicated a significant difference in survival functions between the CDR=0 and CDR=1 groups after baseline age was controlled for (P<.001). Cox regression analysis also indicated that baseline age was a significant risk factor for a rating of "not safe" (P=.002). CONCLUSION: This study provides longitudinal evidence for a decline in driving performance over time, primarily in early-stage DAT, and supports the need not only for driving assessments, but also for reevaluation of individuals with very mild and mild DAT.     

Characteristics of motor vehicle crashes of drivers with dementia of the Alzheimer type

OBJECTIVE: To determine whether there is a difference in crash rates and characteristics between drivers with dementia of the Alzheimer type (DAT) and nondemented older persons who were controls. DESIGN: A pilot study using a 5-year retrospective analysis of state-recorded crash data and crash characteristics followed by patient enrollment into a study on road test skills. SETTING: Alzheimer's Disease Research Center at Washington University in St. Louis, Missouri. Subjects were enrolled as volunteers in a longitudinal study of aging and DAT. PARTICIPANTS: One hundred twenty-one subjects (58 nondemented, older drivers and 63 drivers with DAT) with a mean age of 77 years met the inclusion criteria for this study. DAT was diagnosed using validated clinical diagnostic criteria and was staged by the Clinical Dementia Rating (CDR) Scale. All subjects with DAT were in the very mild (CDR = 0.5) or mild (CDR = 1) stages. MAIN OUTCOME MEASURE: State-recorded traffic crashes. Also, a daily driving diary was completed by each subject and used to estimate miles traveled per year. RESULTS: Subjects diagnosed with mild DAT (CDR = 1) reported less roadway exposure (average number of miles driven per year) than did drivers with very mild DAT (CDR = 0.5) or controls. Crashes in both groups were infrequent, with 0.07 state-recorded crashes per driver per year in the nondemented group (CDR = 0), 0.06 in the very mild DAT group (CDR = 0.5), and 0.04 in the mild DAT group (CDR = 1). There was no statistical difference in the crash frequency between groups, even when adjusting for exposure. Drivers with DAT had trends toward more at-fault crashes, crashes with injuries, and crashes in which the officer on the scene cited failure to yield. CONCLUSIONS: In our sample, individuals with very mild or mild DAT who continued to drive seemed to have crash rates similar to those of the controls. There may be significant differences between the causes and the consequences of crashes involving drivers with DAT when compared with cognitively intact age-matched controls, but none were found in this pilot study. Further research on crash characteristics is needed in larger samples of community-based drivers with DAT across wider ranges of dementia severity to address issues such as driving competency and public safety.     

Classifying late-onset dementia with MRI: Is arteriosclerotic brain degeneration the most common cause of Alzheimer’s syndrome?

Our aim was to use early magnetic resonance imaging (MRI) to investigate the causes of cognitive decline in elderly people with mild cognitive impairment (MCI). Baseline structural and flow quantification MR sequences, and clinical and neuropsychological follow-up for at least two years, were performed on 62 elderly subjects with MCI. Of these subjects, 17 progressed to dementia, and 15 of these progressed to dementia of the Alzheimer type (DAT). Conversion to clinically diagnosed DAT was related to six distinct MR profiles, including one profile suggesting severe AD (20% of these converters) and five profiles suggesting severe cerebrovascular dysfunction. Two profiles suggested arteriosclerotic brain degeneration, one profile suggested severe venous windkessel dysfunction, and two suggested marked cerebral hypoperfusion associated with very low craniospinal compliance or marked brain atrophy. As compared with vascular MR type converters, AD MR type converters showed high executive and mobility predementia performances. Severe whole anteromesial temporal atrophy and predominantly left brain atrophy on visual MR analysis was only observed in AD MR type converters. In conclusion, these observations enhance the pathogenic complexity of the Alzheimer syndrome, and suggest that the role of arteriosclerotic brain degeneration in late life dementia is underestimated.     

Visual retinocortical function in dementia of the Alzheimer type

BACKGROUND: Some histological investigations have reported anomalies in the primary visual pathways of individuals with dementia of the Alzheimer type (DAT), while others have suggested that these visual structures are spared by the disease process. OBJECTIVES: This study was conducted to address this issue of substantial controversy. We determined in vivo whether DAT alters the functioning of the primary visual pathways by evaluating pattern-reversal electroretinograms (ERGs) and cortical visual evoked potentials (VEPs). METHODS: Twenty-seven individuals with mild to moderate DAT and 27 age- and sex-matched control subjects were included in the investigation. ERG and VEP recordings were obtained from all participants with the use of a clinical electrodiagnostic system. Stimulus conditions were biased towards a preferential response from the magnocellular and parvocellular subdivisions of the visual system. Results: Amplitude and latency of the ERG were not affected by DAT. The VEP amplitude was not attenuated in DAT individuals, but there was a delay in the latency of the VEPs arising from both magnocellular and parvocellular streams of visual processing. CONCLUSION: Our results indicate that while the inner retina appears to be spared by the disease process, the visual function is altered upstream in the retinocortical visual pathways of individuals with DAT.     

Brain Metabolism of Less-Educated Patients With Alzheimer Dementia Studied by Positron Emission Tomography

Alzheimer dementia (AD) is the commonest form of dementia. Although illiteracy is associated with high prevalence of dementia of the Alzheimer type (DAT), their relationship is still unclear. Nevertheless, mild DAT in illiterate participants seems to be due to brain atrophy.In this study, we compared the impact of brain metabolism efficiency in healthy participants and less-educated patients with mild DAT using 2-fluoro-2-deoxy-d-glucose (¹⁸F-FDG-PET) positron emission tomography. Out of 43 eligible less-educated participants with dementia, only 23 (14 women and 9 men) met Diagnostic and Statistical Manual (DSM)-III-R or DSM-IV criteria for DAT and AD and were included. Participants with intracranial insults were excluded by brain magnetic resonance imaging and participants with metabolic or systemic conditions were excluded by blood sampling. In addition, 16 cognitively normal elderly (age >70 years), including 7 women and 9 men, were enrolled in the sham group. The PET imaging data were analyzed using statistical parametric mapping (SPM8) to determine reliability and specificity.Glucose metabolic rate was low in the DAT group, especially in the middle temporal gyrus, middle frontal gyrus, superior frontal gyrus, inferior frontal gyrus, posterior cingulate gyrus, angular gyrus, parahippocampal gyrus, middle occipital gyrus, rectal gyrus, and lingual gyrus.Our results showed that DAT patients with less education not only have prominent clinical signs and symptoms related to dementia but also decreased gray matter metabolism.     

Interdisciplinary research strategies in geriatric psychiatry--studies and results in dementia and depressed patients

Eighty-one patients (mean age: 66 +/- 9 years) who had been in gerontopsychiatric in-patient care were included in the study. As well as physical, psychiatric and neurological examinations, EEG, brain CT scanning and the determination of the Ischemic Scale were performed, in order to confirm the clinical diagnosis of dementia of Alzheimer type (DAT), dementia of vascular type (DVT) or multi-infarct dementia (MID), and depression in old age, as based on the DSM III criteria. A comprehensive psychological test battery was administered, to one section of the subjects. Our results indicate that EEG and Ischemic Score can differentiate patients with DAT and DVT to a satisfactory degree, whereas CT findings and psychometric assessment were apt to confirm the overall diagnosis of dementia (DAT/DVT) and depression. Patients with dementia showed memory impairment to a greater extent than depressive patients, as could be proved by a memory test (Syndrom-Kurztest). However, a dementia screening test (Information-Memory-Concentration Test) could more accurately differentiate dementia and depression. The application of a comprehensive psychometric testing procedure did not prove to be an effective diagnostic tool in the assessment of various stages of dementia. Short dementia tests and rating scales seem to be appropriate to distinguish depression from dementia, especially in cases of mild to moderate dementia. In patients with very mild and insignificant organic brain disturbances these screening methods fall short of diagnostic validity. Beyond this, there is a current need for assessment instruments in the evaluation of alterations in personality and affectivity, such as are seen in depression.     

Labeled cortical mantle distance maps of the cingulate quantify differences between dementia of the Alzheimer type and healthy aging

The cingulate gyri in 37 subjects with and without early dementia of the Alzheimer type (DAT) were studied by using MRI at 1.0 mm3 isotropic resolution. Groups were segregated into young controls (n = 10), age-matched normal controls (n = 10), very mild DAT (n = 8), and mild DAT (n = 9). By using automated Bayesian segmentation of the cortex and gray matter/white matter (GM/WM) isosurface generation, tissue compartments were labeled into gray, white, and cerebrospinal fluid as a function of distance from the GM/WM isosurface. Cortical mantle distance maps are generated profiling the GM volume and cortical mantle distribution as a function of distance from the cortical surface. Probabilistic tests based on generalizations of Wilcoxon-Mann-Whitney tests were applied to quantify cortical mantle distribution changes with normal and abnormal aging. We find no significant change between young controls and healthy aging as measured by the GM volume and cortical mantle distribution as a function of distance in both anterior and posterior regions of the cingulate. Significant progression of GM loss is seen in the very mild DAT and mild DAT groups in all areas of the cingulate. Posterior regions show both GM volume loss as well as significant cortical mantle distribution decrease with the onset of mild DAT. The "shape of the cortical mantle" as measured by the cortical mantle distance profiles manifests a pronounced increase in variability with mild DAT.     

Non invasive study of carotid arteries by echo-doppler and metabolic abnormalities in patients with dementia

In order to evaluate the prevalence of common and/or internal carotid stenoses together with metabolic abnormalities in dementia nineteen patients were investigated. Dementia and differential diagnosis between Alzheimer type (DAT) and multi-infarctual (MID) dementia were performed on the basis of Computerized Tomography scan, behavioural anamnesis, neurological and neuropsychological examinations. Eight patients were diagnosed as MID and 11 as DAT. Noninvasive study of neck arteries was performed in supine position by a Duplex Scanner, able of detecting a wide range of stenosis, even when very mild. Arterial hypertension, hyperlipidemia, diabetes and high hematocrit level were present in both groups, although to a higher extent in MID (p 0.05). Results from Duplex Scanner demonstrate 12 vascular stenoses 16-49% and one between 50-99% (13/76), being vascular abnormalities equally distributed among DAT and MID patients. These data suggest that patients with metabolic abnormalities and arteriosclerosis can develop dementia not necessarily of vascular type. On the other hand, MID patients do not present higher number of stenosis as compared to DAT, indicating that vascular disease of carotid arteries is not prominent in the clinical context of dementia.     

Inhibition of normal polymorphonuclear leukocyte philothermal response by serum from dementia of the Alzheimer-type patients

The effects of sera obtained from patients with dementia of the Alzheimer type (DAT) as well as sera from young and elderly mentally normal individuals on the philothermal response of polymorphonuclear leukocytes (PMNs) of three healthy volunteers were assessed. The sera from DAT patients strikingly inhibited the philothermal response of normal PMNs while no inhibition was seen with sera from normal individuals. Clearly factor(s) in the sera of patients with DAT are capable of inhibiting the philothermal response, but the nature of the inhibitor(s) remains to be elucidated. These preliminary findings suggest that this experimental technique may represent a diagnostic test for DAT.     

Factors attenuating the validity of the Geriatric Depression Scale in a dementia population.

OBJECTIVE: The validity of the Geriatric Depression Scale (GDS) in cognitively impaired patients has been questioned. We investigated possible factors (memory loss, dementia severity, unawareness of illness) attenuating the validity of the GDS in patients with dementia. PATIENTS: Eighty-three patients who met research diagnostic criteria for "probable Alzheimer's disease." Subjects with major depressive disorder were excluded. Dementia severity ranged from mild to moderate. SETTING: Outpatient clinics, including institutional settings and private research settings. MEASUREMENTS: Depression--GDS; Hamilton Depression Scale. Memory--Wechsler Memory Scale; Benton Visual Retention Test. Dementia severity--Mini-Mental State Examination. Self-awareness of cognitive deficits--Difference score between a self-report memory questionnaire and an informant-rated memory questionnaire. RESULTS: Multiple regression analysis revealed that Hamilton scores were the major predictor of GDS scores. Memory scores and self-awareness scores were also significant predictors. Dementia severity scores were not a significant predictor. CONCLUSIONS: The GDS is a valid measure of mild-to-moderate depressive symptoms in Alzheimer patients with mild-to-moderate dementia. However, Alzheimer patients who disavow cognitive deficits also tend to disavow depressive symptoms, and the GDS should be used with caution in such patients. Finally, the argument that memory impairment precludes accurate self-report of recent mood is negated by our finding that many patients accurately reported depressive symptoms and that worse memory was associated with more self-reported depressive symptoms.     

轻度认知功能障碍向阿尔茨海默病转化的预测研究进展

轻度认知功能障碍（MCI）是介于正常衰老与痴呆之间的认知功能缺损状态,MCI进展为阿尔茨海默病（AD）的危险性较高,故MCI阶段可能是进行AD预防性治疗的最合适阶段,因而成为研究的焦点。本文就近年来MCI向AD的转化预测研究做一综述,主要包括五个方面：神经心理学测试、生物标志物检查、神经影像学检查、脑电生理学检查及其治疗进展。     

Reaction to a dementia diagnosis in individuals with Alzheimer's disease and mild cognitive impairment

OBJECTIVES: To examine short-term changes in depression and anxiety after receiving a dementia diagnosis.
DESIGN: Pre/post survey design.
SETTING: Alzheimer's Disease Research Center.
PARTICIPANTS: Ninety individuals and their companions.
MEASUREMENTS: Fifteen-item Geriatric Depression Scale and 20-item "state" version of the State-Trait Anxiety Inventory.
RESULTS: Sixty-nine percent of the individuals were diagnosed with dementia; two-thirds of those were in the earliest symptomatic stages of dementia that, in other settings, is considered to represent mild cognitive impairment. No significant changes in depression were noted in individuals or their companions, regardless of diagnostic outcome or dementia severity. Anxiety decreased substantially after diagnostic feedback in most groups.
CONCLUSION: Disclosure of a dementia diagnosis does not prompt a catastrophic emotional reaction in most people, even those who are only mildly impaired, and may provide some relief once an explanation for symptoms is known and a treatment plan is developed.     

High-dose naloxone in older normal subjects: implications for Alzheimer's disease

The behavioral and cognitive effects of naloxone HCl, in doses of 5 micrograms/kg, 0.1 mg/kg, and 2.0 mg/kg administered as an IV bolus, were assessed in a double-blind, placebo-controlled, randomized study of eight normal subjects ranging in age from 44 to 74 years (mean 63). Naloxone produced mild behavioral effects with slight cognitive impairment after the 2.0 mg/kg dose only. The threshold, dose dependency, characteristics, and magnitude of these behavioral effects were similar to what has previously been reported in young normal subjects, but markedly different from those observed in patients with dementia of the Alzheimer type (DAT) matched in age to the current study sample. These data suggest that the metabolic fate of naloxone is not substantially affected by age within the range studied. The findings of this study provide further support for a role for endogenous opiate systems in the modulation of behavior and cognition, and suggest that the unusual behavioral sensitivity of patients with DAT to naloxone cannot be accounted for by the effect of age.     

Comparison of the quick mild cognitive impairment (Qmci) screen and the SMMSE in screening for mild cognitive impairment

Introduction: differentiating mild cognitive impairment (MCI) from normal cognition (NC) is difficult. The AB Cognitive Screen (ABCS) 135, sensitive in differentiating MCI from dementia, was modified to improve sensitivity and specificity, producing the quick mild cognitive impairment (Qmci) screen. Objective: this study compared the sensitivity and specificity of the Qmci with the Standardised MMSE and ABCS 135, to differentiate NC, MCI and dementia. Methods: weightings and subtests of the ABCS 135 were changed and a new section 'logical memory' added, creating the Qmci. From four memory clinics in Ontario, Canada, 335 subjects (154 with MCI, 181 with dementia) were recruited and underwent comprehensive assessment. Caregivers, attending with the subjects, without cognitive symptoms, were recruited as controls (n?=?630). Results: the Qmci was more sensitive than the SMMSE and ABCS 135, in differentiating MCI from NC, with an area under the curve (AUC) of 0.86 compared with 0.67 and 0.83, respectively, and in differentiating MCI from mild dementia, AUC of 0.92 versus 0.91 and 0.91. The ability of the Qmci to identify MCI was better for those over 75 years. Conclusion: the Qmci is more sensitive than the SMMSE in differentiating MCI and NC, making it a useful test, for MCI in clinical practice, especially for older adults.     

Mild cognitive impairment in older people

CONTEXT: As public awareness of Alzheimer's disease increases, more people are asking for help and advice about memory problems. Memory complaints may be secondary to psychiatric, psychological, and physical conditions and is an almost universal early symptom of dementia. The concept of amnestic mild cognitive impairment attempts to describe those people in whom memory loss is not of such severity to merit a diagnosis of dementia. The importance of this group of people is not just the need to develop interventions which ameliorate individual suffering but that they represent a population at high risk of developing dementia, especially Alzheimer's disease, and are an appropriate target for dementia prevention strategies. STARTING POINT: K Kantarci and colleagues (Dement Geriatr Cogn Disord 2002; 14: 198-207) looked at the diagnostic accuracy of magnetic-resonance hippocampal volumetry and spectroscopy in patients with mild cognitive impairment, in normal older people, and in patients with Alzheimer's disease. Hippocampal volumes and N-acetyl aspartate/creatine spectroscopy were the most sensitive assessments discriminating people with mild cognitive impairment from Alzheimer's disease. Combination assessments were better at discriminating these two groups from normal controls. The histological underpinning of cognitive symptoms in older people has been demonstrated by the Cognitive Function and Ageing study (Lancet 2001; 357: 169-75), which showed that a third of people with no clinical evidence of dementia had histopathological hallmarks of Alzheimer's disease. WHERE NEXT? 25 million people across the world have dementia. Mild cognitive impairment, if a validated concept, represents an opportunity for preventing dementia. As more information becomes available about the cause of Alzheimer's disease and prospects emerge for prevention, identification of predementia states offers considerable scope to reduce the individual and societal cost of the illness. Continued validation of the criteria for mild cognitive impairment and studies of intervention should be a priority. As more evidence becomes available highlighting the relatively arbitrary nature of dementia diagnosis (based largely on interference with activities) and interventions become available for the prevention of dementia, mild cognitive impairment and related conditions will become more important.     

2013年第1期中文目录

随着人口老龄化的到来,老年性相关疾病的发生越来越突出,轻度老年认知功能障碍是老年性痴呆的高危人群,是介于正常认知老化与轻度痴呆之间的一种临床状态。然而,在临床常规工作对轻度老年认知功能障碍认识严重不足,故加强对老年早期认知功能障碍的认识水平,提高对老年人早期认知功能障碍的评估与筛查,是尽早干预和预防老年性痴呆发生的重要保障。     

Alcohol-Related Dementia in the Institutionalized Elderly

This study examined the distribution of alcohol-related and other dementias in a sample of 130 cognitively impaired residents of long-term care facilities in a Northern Ontario community. Study procedures entailed standardized psychiatric, neurological, and neuropsychological evaluations. Diagnoses of dementia of the Alzheimer type (DAT) and vascular dementia were based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The diagnosis of alcohol-related dementia (ARD) was based on extensive review of medical history to assess before alcohol abuse and stabilization or improvement in cognitive functioning following institutionalization in conjunction with no other identifiable cause of dementia. ARD comprised 24% of this population compared with DAT (35%), vascular dementia (19%), and other causes (22%). The ARD group was, on average, 10 years younger than the other groups. It had nearly twice the average length of institutionalization and had milder cognitive impairment on both clinical ratings and neuropsychological tests. A diagnosis of ARD was present in the medical records for only 25% of patients in this group. These findings suggest that ARD may be more common than previously suspected in the distribution of dementias in long-term care facilities.     

Equilibrium and limb coordination in mild cognitive impairment and mild Alzheimer's disease

OBJECTIVE: To examine changes in equilibrium and limb coordination in normal aging, mild cognitive impairment, and moderate cognitive impairment associated with early probable Alzheimer's disease (AD), by means of parametric clinical measures. DESIGN: Case series SETTING: Out-patient clinic. PARTICIPANTS: A consecutive sample of 365 community-residing ambulatory volunteers (137 men, 228 women; mean age 70.4 +/- 9.4 years; mean educational attainment 14.6 +/- 3.1 years), who were followed in an ongoing longitudinal study of aging and AD, comprising cognitively intact individuals, persons with mild cognitive impairment, and patients with mild AD. MEASUREMENTS: For general magnitude of cognitive function, the Global Deterioration Scale (GDS). For cognition, the Mini-Mental State Examination (MMSE). Equilibrium was assessed with parametric measurements of single leg stance (SLS) and tandem walking (TW). Limb coordination was assessed with parametric measurements of foot tapping (FT), alternating pronation and supination (PS), and sequential finger to thumb tapping (FTH). MAIN RESULTS: After adjustment for age, persons with mild cognitive impairment or mild AD had significantly poorer performance on parametric clinical tests of equilibrium and limb coordination compared with cognitively intact individuals (P < .05). CONCLUSIONS: Changes in equilibrium and limb coordination are clinically demonstrable in persons with mild cognitive impairment and mild AD using simple parametric tests. Such tests could potentially identify individuals with increased risk of falling. Early diagnosis and treatment of conditions that can jeopardize equilibrium and limb coordination, as well as balance and coordination training, might help cognitively impaired older people to maintain optimal function and may decrease the risk of falls and injuries.