Depressive symptoms among cognitively normal versus cognitively impaired elderly subjects

OBJECTIVES: The present cross-sectional study analyzed the prevalence and severity of depressive symptoms among patients with Alzheimer's disease (DAT), vascular dementia (VAD), and among the cognitively normal elderly. Putative risk factors contributing to depression were likewise evaluated. METHODS: Seventy-six DAT patients, 51 VAD patients, and 121 cognitively normal subjects were admitted to the study. Questionnaires concerning demography and their vascular and familial risk factors together with results of neuropsychological testing by combined Mini-Mental Status Examinations (MMSE), Cognitive Capacity Screening Examinations (CCSE), and Hamilton Depression Rating Scales (HDRS) were obtained so that resulting data would be statistically analyzed. RESULTS: Prevalence of depressive symptoms among VAD, DAT, and cognitively normal elderly were 31.4%, 19.9%, and 13.2%, respectively. 25.5% of VAD and 13.2% of DAT patients had depression of mild to moderate degrees. Regression analysis revealed that diagnosis of VAD and DAT, heart disease, and past history of depression was significantly associated with high HDRS scores. There was no correlation between degree of depression and severity of cognitive impairments. CONCLUSION: Mild to moderate depression is a common comorbidity with organic dementia, especially VAD, but associated depression is independent of severity of cognitive impairments.     

Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats

There is a tendency for increased hypothalamic-pituitary-adrenal (HPA) activity with age in the rat, and the resulting elevations in circulating glucocorticoid levels have been implicated in the occurrence of hippocampal pathology and memory deficits. In the experiments reported here, we examined whether HPA dysfunction is selectively associated with cognitive impairments in a population of aged rats. Fifty-eight 23-27-month-old male Long-Evans rats were screened for spatial memory impairments using the Morris swim maze, and 2 groups of aged animals were selected; aged, cognitively impaired (AI) animals whose performance was significantly different (greater than 2 SD) from that of 6-month-old controls and aged, cognitively unimpaired (AU) animals whose performance was comparable to that of the young controls (a difference of less than 0.5 SD). Twenty-eight percent of the animals tested were designated as AI and 20% as AU. Histological analysis of a subset of these animals showed that, while both AU and AI animals showed neuron loss in the pyramidal cell fields of the hippocampus, the loss was significantly greater in the AI animals. The AI animals showed clear evidence of increased HPA activity. Thus, basal ACTH and corticosterone levels were significantly higher in the AI animals compared with both AU animals and young controls, especially during the dark phase of the cycle. The AI, AU, and young animals exhibited comparable corticosterone levels during a 20-min immobilization stress; however, following the termination of the stressor, corticosterone levels in AI animals were significantly elevated compared with both AU animals and controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropathology of cognitively normal elderly

Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed. cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage 相似文献   

Clinically diagnosed Alzheimer disease: neuropathologic findings in 650 cases.

Despite the introduction of formal clinical criteria for Alzheimer disease (AD), the clinical diagnosis of AD remains one of exclusion of other dementias. To determine the accuracy of a clinical diagnosis of AD as made by practicing physicians, we reviewed the clinicopathologic records of a dementia brain bank and summarized the literature. Of 650 demented patients diagnosed during life as having AD, at autopsy 505 (78%) had AD with or without other neuropathologic conditions; only 390 (60%) of these had AD as the only neuropathologic condition. Of the remaining 145 (22%) patients with no neuropathologic evidence of AD, 39 had the nigrostriatal changes of Parkinson disease (PD), 25 had nonspecific degenerations, 15 had Pick disease, 14 had multiple infarcts, and 11 lacked any neuropathologic abnormality. Although the overall clinical accuracy for AD was lower than that summarized from the literature, clinical accuracy improved significantly between 1986 and 1990. In our broad sample of practitioners, accuracy of clinical diagnosis of AD may be improving, but continues to be hampered by difficulty in distinguishing the dementia of AD from certain dementing conditions and from AD mixed with other neuropathologic conditions.     

Stressful events and severity of memory complaints in cognitively normal adults aged from 25 to 85 years

The relationships between subjective cognitive difficulties and stressful events (SE) have rarely been examined. Broadbent et al. (1982) suggested that such difficulties disclose a high sensitivity to stress, independently of depression and personality. Objective: To explore the relationships between the severity of memory complaints and SE occurred during the previous year. Methods: 260 cognitively normal subjects, aged from 25 to 85 years were examined in a Memory clinic through one year. The severity of memory complaints was globally assessed by asking the participants to qualify the intensity of their subjective difficulties as major or minor, and quantitatively, by using a 8-item subjective memory scale. SE were assessed by asking the subjects whether they experienced one or more events that had negative effects on their physic or mental well-being in the domains of health, family, social environment and financial position during the last 12 months. Affective status was assessed by the Zung's depression (ZD) and anxiety (ZA) scales, and by a Wellbeing questionnaire, QBE. Cognition was assessed using a semi-computerized battery exploring memory and several cognitive abilities. Results: SE were reported in 156 subjects (60%). No differences were found between subjects with or without SE according to age, genre, familial status and activity, as well as cognitive performance. Subjects with SE reported more severe complaints and higher scores on ZD and ZA scales, and lower scores on the QBE. Severity of memory complaints was mainly correlated to QBE in subjects with SE and to ZA scale in subjects without. Subjects with age <?50 years reported more SE than subjects aged ≥ 50 years. No difference was found between the two age groups according to the type of SE in the domain of health, family, and finances, but higher SE were reported in younger subjects in the domain of social environment. The main correlates of the severity of memory complaints were depression in younger subjects with or without SE, and anxiety in absence of SE and QBE in presence of SE in older subjects. However, the affective scores explained only a weak part of the variance of the severity of memory complaints. Conclusion: SE do not seem to play a direct role in the severity of memory complaints, but they increase the affective disturbances. We suggest that anxiety and various factors such as decrease in self-esteem and modification of self-identity result in a psychological vulnerability which contribute to memory complaints.     

Hippocampal shape alterations are associated with regional Aβ load in cognitively normal elderly individuals

Aβ deposition is a driving force of Alzheimer's disease pathology and can be detected early by amyloid positron emission tomography. Identifying presymptomatic structural brain changes associated with Aβ deposition might lead to a better understanding of its consequences and provide early diagnostic information. In this respect we analyzed measures of cortical thickness and subcortical volumes along with hippocampal, thalamic and striatal shape and surface area by applying novel analysis strategies for structural magnetic resonance imaging. We included 69 cognitively normal elderly subjects after careful clinical and neuropsychological workup. Standardized uptake value ratios (cerebellar reference) for uptake of 11‐C‐Pittsburgh Compound B (PiB) were calculated from positron emission tomographic data for a cortical measurement and for bilateral hippocampus, thalamus and striatum. Associations to shape, surface area, volume and cortical thickness were tested using regression models that included significant predictors as covariates. Left anterior hippocampal shape was associated with regional PiB uptake (P < 0.05, FDR corrected), whereas volumes of the hippocampi and their subregions were not associated with cortical or regional PiB uptake (all P > 0.05, FDR corrected). Within the entorhinal cortical region of both hemispheres, thickness was negatively associated with cortical PiB uptake (P < 0.05, FDR corrected). Hence, localized shape measures and cortical thickness may be potential biomarkers of presymptomatic Alzheimer's disease.     

The prevalence of Alzheimer neuropathologic lesions is similar in blacks and whites

Alzheimer disease is the most common dementia in older Americans, but its impact on blacks is not clearly understood. We examined prospectively 200 autopsy brains at the Office of the Chief Medical Examiner in Maryland and compared the frequency and severity of Alzheimer lesions in blacks and whites. Histologic sections of the hippocampus and entorhinal and neocortices were immunostained for Abeta and tau proteins. Subjects were genotyped for ApoE. Abeta deposits were rated as none, sparse, moderate, or frequent; tau lesions were rated into 4 groups corresponding to Braak scores; and Abeta angiopathy was classified as present or absent. Outcome scores were treated as ordinal variables and analyzed by proportional odds logistic regression. Abeta plaques were present in 60% of black males, 58% of white males, 74% of black females, and 74% of white females. Tau lesions were present in 96% of black males, 88% of white males, 96% of black females, and 96% of white females. Neither race nor gender was a significant factor in the frequency or severity of Alzheimer lesions, and ApoE4 increased the risk for Alzheimer lesions similarly in blacks and whites.     

Vascular dementia: neuropathologic alterations and metabolic brain changes.

After reviewing the concepts of dementia, in general, and vascular dementia, in particular, this review discusses potential future approaches that may contribute to an improved definition of the clinical syndrome and the neuropathological features of vascular dementia. Specific brain alterations in high-energy phosphate compounds, as measured by nuclear magnetic resonance, may contribute to the separation between dementias with neurodegenerative diseases and those with ischemic (vascular or hemodynamic) disorders.     

The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects

The 4.2-kilodalton (kDa) polypeptide associated with the cerebral amyloid deposits of Alzheimer's disease (AD) derives from a much larger protein that is encoded by a gene on chromosome 21. In the present study, we have used antibodies raised against portions of the amyloid protein precursor (APP) to map its normal distribution and to gain further insights into the events that lead to amyloid deposition. Antibodies raised against several different portions of APP reacted with proteins having apparent molecular sizes of 65, 67, and 132 kDa on Western blots. In sections through the normal human brain, immunocytochemistry revealed punctate concentrations of the protein in pyramidal cells of the neocortex, particularly in associative regions, and intense staining in the CA1 pyramidal cells of the hippocampus. By electron microscopy, this punctate distribution coincided with dense concentrations of the protein in secondary lysosomes. In the hippocampus of several AD cases examined, abnormally dense immunostaining in enlarged intracellular domains accompanied a severe atrophy of the CA1 neurons. These data suggest that accumulations of APP in lysosomes of particular neurons may, in AD, lead to proteolytic events that form the insoluble 4.2-kDa amyloid peptide.     

Differences in olfactory test performance between normal aged,Alzheimer and vascular type dementia individuals

A comparison was made between 3 groups of elderly subjects — normal controls aged 69–79 years, patients with vascular dementia aged 64–84 years and patients with probable senile dementia of Alzheimer type (SDAT) aged 70–90 years — by means of several tests of olfactory functions. Significant group differences were found at all levels assessed — olfactory thresholds, smell recognition, smell identification, naming of smells — with the normal aged performing best and the SDAT group scoring lowest throughout. The differences were most pronounced with regard to smell recognition and smell identification where minimal or no overlap at all between controls and SDAT patients was found. Differences in age and severity of dementia did not fully account for the findings, suggesting that differential diagnosis of Alzheimer - type dementia could be facilitated and improved by the use of olfactory tasks. Neurophysiological and - pathological findings support a close association or even identity of brain structures involved in olfaction and affected in Alzheimer's disease.     

Covarying alterations in Aβ deposition,glucose metabolism,and gray matter volume in cognitively normal elderly

β‐Amyloid (Aβ), a feature of Alzheimer's disease (AD) pathology, may precede reduced glucose metabolism and gray matter (GM) volume and cognitive decline in patients with AD. Accumulation of Aβ, however, has been also reported in cognitively intact older people, although it remains unresolved whether and how Aβ deposition, glucose metabolism, and GM volume relate to one another in cognitively normal elderly. Fifty‐two cognitively normal older adults underwent Pittsburgh Compound B–positron emission tomography (PIB‐PET), [¹⁸F]fluorodeoxyglucose‐PET, and structural magnetic resonance imaging to measure whole‐brain amyloid deposition, glucose metabolism, and GM volume, respectively. Covariance patterns of these measures in association with global amyloid burden measured by PIB index were extracted using principal component analysis–based multivariate methods. Higher global amyloid burden was associated with relative increases of amyloid deposition and glucose metabolism and relative decreases of GM volume in brain regions collectively known as the default mode network including the posterior cingulate/precuneus, lateral parietal cortices, and medial frontal cortex. Relative increases of amyloid deposition and glucose metabolism were also noted in the lateral prefrontal cortices, and relative decreases of GM volume were pronounced in hippocampus. The degree of expression of the topographical patterns of the PIB data was further associated with visual memory performance when controlling for age, sex, and education. The present findings suggest that cognitively normal older adults with greater amyloid deposition are relatively hypermetabolic in frontal and parietal brain regions while undergoing GM volume loss in overlapping brain regions. Hum Brain Mapp 35:297–308, 2014. © 2012 Wiley Periodicals, Inc.