Medial temporal lobe is vulnerable to vascular risk factors in men: a population-based study.

BACKGROUND AND PURPOSE: Vascular risk factors (VRFs) are known to cause cerebral microvascular disease, but evidence supporting an effect of VRFs on regional brain atrophy is mixed. We investigate whether an aggregation of VRFs is associated with volume of hippocampus and entorhinal cortex in elderly people living in the community. METHODS: This cross-sectional study consists of 523 participants (age ≥60 years, 59.3% women) of the SNAC-K Study in central Stockholm, Sweden, who were free of clinical stroke and cognitive impairment. We collected data on VRFs through interviews, clinical examination and inpatient register system. Hippocampal and entorhinal cortex volume was manually measured on magnetic resonance images. Data were analysed with general linear regression models controlling for demographics and total intracranial volume. RESULTS: In men, high total cholesterol and diabetes were significantly or marginally associated with smaller hippocampus and entorhinal cortex; when current smoking, binge alcohol drinking, high cholesterol and diabetes were aggregated, an increasing number of VRFs were significantly associated with decreasing volume of hippocampus and entorhinal cortex (P for linear trend <0.01). In women, none of individual VRFs or their aggregation was significantly associated with the volume of these brain regions, except former smoking that was significantly associated with a larger volume of these regions. CONCLUSIONS: Aggregation of VRFs is associated with reduced hippocampal and entorhinal cortex volume in apparently healthy elderly men, but not in women. This implies that in men, the medial temporal lobe is vulnerable to cardiovascular risk factors.

Personality and lifestyle in relation to dementia incidence.

OBJECTIVE: High neuroticism has been associated with a greater risk of dementia, and an active/socially integrated lifestyle with a lower risk of dementia. The aim of the current study was to explore the separate and combined effects of neuroticism and extraversion on the risk of dementia, and to examine whether lifestyle factors may modify this association. METHODS: A population-based cohort of 506 older people with no dementia from the Kungsholmen Project, Stockholm, Sweden, was followed up for an average of 6 years. Personality traits were assessed using the Eysenck Personality Inventory. Dementia was diagnosed by specialists according to DSM-III-R criteria. RESULTS: Neither high neuroticism nor low extraversion alone was related to significantly higher incidence of dementia. However, among people with an inactive or socially isolated lifestyle, low neuroticism was associated with a decreased dementia risk (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.27-0.96). When compared to persons with high neuroticism and high extraversion, a decreased risk of dementia was detected in individuals with low neuroticism and high extraversion (HR = 0.51, 95% CI = 0.28-0.94), but not among persons with low neuroticism and low extraversion (HR = 0.95, 95% CI = 0.57-1.60), nor high neuroticism and low extraversion (HR = 0.97 95% CI = 0.57-1.65). Stratified analysis by lifestyle showed that the inverse association of low neuroticism and high extraversion in combination was present only among the inactive or socially isolated persons. CONCLUSION: Low neuroticism in combination with high extraversion is the personality trait associated with the lowest dementia risk; however, among socially isolated individuals even low neuroticism alone seems to decrease dementia risk.

Life satisfaction among the very old: a survey on a cognitively intact sample aged 90 years or above.

The purpose of the study was to measure life satisfaction and the factors believed to influence it. The study involved 105 very old people, ninety years and above, who were not cognitively impaired, living in the inner part of Stockholm, Sweden. In order to assess life satisfaction, the Life Satisfaction Index-B (LSI-B) and Life Satisfaction Index-Z (LSI-Z) were used. Information about life events, activities, personality and social contacts were collected in order to determine their relative influence on life satisfaction. Factors associated with life satisfaction were also investigated in a content analysis to find out what the elderly themselves believe gives them life satisfaction. Results showedthat health and an emotionally stable personality were, independently of other factors, the most important factors for life satisfaction among the very old.

Sex differences favoring women in verbal but not in visuospatial episodic memory.

Sex differences favoring women have been found in a number of studies of episodic memory. This study examined sex differences in verbal, nonverbal, and visuospatial episodic memory tasks. Results showed that although women performed at a higher level on a composite verbal and nonverbal episodic memory score, men performed at a higher level on a composite score of episodic memory tasks requiring visuospatial processing. Thus, men can use their superior visuospatial abilities to excel in highly visuospatial episodic memory tasks, whereas women seem to excel in episodic memory tasks in which a verbalization of the material is possible.

The Bangla adaptation of Mini-Mental State Examination (BAMSE): an instrument to assess cognitive function in illiterate and literate individuals.

The Mini-Mental State Examination (MMSE) is a brief global instrument used to assess cognitive abilities in the elderly, requiring literacy as a prerequisite. Such a precondition is impractical for populations with widespread illiteracy. The present study aimed to adapt the MMSE for the cultural context of Bangladesh and for use in populations irrespective of literacy skills. In the Bangla Adaptation of Mini-mental State Examination (BAMSE), the MMSE items were changed in such a way that they would be applicable for illiterate individuals, as well as being culturally relevant in Bangladesh. Altogether 672 elderly, 262 literate and 410 illiterate individuals were tested with the BAMSE. To enable comparison between the BAMSE and MMSE, the literate elderly were tested with both instruments. Test-retest reliability of the BAMSE was assessed in 54 randomly selected individuals. The results showed that, in comparison to the MMSE, the BAMSE demonstrated satisfactory test properties, although reliable differences were found on some of the individual items when the two instruments were compared. The association between the two instruments was good (r=0.57) and the test-retest reliability was satisfactory (r=0.70). More importantly, the BAMSE was found to be less sensitive to age and education than the MMSE. Finally, our results suggest that in the socio-cultural context of Bangladesh, irrespective of literacy skills, the BAMSE is an instrument that can be used to assess cognitive function of the normal elderly.

Brain activation during episodic memory retrieval: sex differences.

Behavioral studies have shown a tendency for women to outperform men on episodic memory tasks. Here, data from a series of positron emission tomography (PET) studies were analyzed to examine sex differences in brain activity associated with episodic memory retrieval (yes/no recognition). A total of 17 women and 17 men were included in the analyses. The strongest effect of the design was a retrieval-related increase in activity, involving right prefrontal and anterior cingulate regions, that was common to women and men. In addition, a significant task-by-sex interaction effect was observed which involved a distributed set of brain regions, including several frontal areas. These results suggest that while the neural correlate of episodic memory retrieval is largely the same for men and women, some differences do exist. Possible explanations for the observed differences are discussed, and it is concluded that biological and experiential factors jointly contribute to sex differences in brain activity.

Sex differences in episodic memory: the impact of verbal and visuospatial ability.

The impact of verbal and visuospatial ability on sex differences in episodic memory was investigated. One hundred men and 100 women, 2040 years old, participated in a series of verbal and visuospatial tasks. Episodic memory was assessed in tasks that, to a greater or lesser extent, were verbal or visuospatial in nature. Results showed that women excelled in verbal production tasks and that men performed at a superior level on a mental rotation task. In addition, women tended to perform at a higher level than men on most episodic memory tasks. Taken together, the results demonstrated that (a) women perform at a higher level than men on most verbal episodic memory tasks and on some episodic memory tasks with a visuospatial component, and (b) women's higher performance on episodic memory tasks cannot fully be explained by their superior performance on verbal production tasks.

Activity patterns in very old people: a survey of cognitively intact subjects aged 90 years or older.

AIM: to measure activity patterns in very old people, the factors related to this and the association of different types of activity with well-being. METHODS: a study of 105 people, aged 90 years or older, who were not cognitively impaired, living in Stockholm. The activities carried out during the previous day were recorded and each activity was rated. RESULTS AND CONCLUSIONS: the degrees of intellectual, social and physical activity are independent of each other. Very elderly people tended to have variable but relatively low activity levels over a day. Good health and not moving home were associated with greater intellectual activity. Extraversion and negative life events (such as death of close friend or family member) were associated with greater social activity, while relatively younger age and better health were associated with greater physical activity. There was positive association between physical activity and well-being.

Mild cognitive impairment--an early stage of Alzheimer's disease?

The hypothesis that mild cognitive impairment (MCI) represents an early stage of Alzheimer's disease (AD) was investigated by reviewing recent research from three sources: asymptomatic and symptomatic individuals carrying mutations that cause AD, hospital-samples of non-demented patients with MCI at the initial examination that are followed longitudinally, and community-based incident cases of AD. Studies with asymptomatic mutation carriers of the amyloid precursor protein and presenilin 1 gene have shown a linear and disease-related decline in most cognitive functions that begins approximately 10 years before the expected clinical onset of AD. However, there is considerable overlap between the level of impairment for mutation carriers and non-carriers of the same age during the early preclinical stage of AD. Hospital-based longitudinal studies have shown that non-demented individuals with isolated mild episodic memory impairment may develop clinically diagnosed AD with widespread cognitive deficits in a few years time. Community-based epidemiological studies on the incidence of AD demonstrate that indices of episodic memory, in addition to measures of general cognitive functioning, are useful in predicting early AD. In contrast, subjective memory impairment or age-associated memory impairment are less powerful predictors of future dementia development. In summary, there is converging evidence to demonstrate that preclinical AD is characterized by a common behavioral phenotype, with cognitive decline in several domains, predominantly in episodic memory. The decline appears to start many years before the clinical onset of AD. Moreover, the progression of the impairment appears to be continuous. Finally, this pattern of performance generalizes across etiology of AD (familial or sporadic), clinical onset (early or late), sample composition (hospital or community), and method of assessment.

Cognitive predictors of incident Alzheimer's disease: a prospective longitudinal study.

The present study examined whether cognitive variables measured at baseline could predict incident cases of Alzheimer's disease (AD) after a 3-year follow-up period. Twenty-six incident AD adults and 179 very old (M = 83.5 years) adults without dementia participated in a population-based study. Cognitive performance was indexed by the Mini-Mental State Examination (MMSE) and multiple indices of memory and visuospatial and verbal performance. A logistic regression analysis that controlled for age, gender, and education indicated that MMSE scores were reliable indicators of who would develop AD. In addition, recall of organizable words, recognition of faces, and letter fluency were reliable predictors of subsequent dementia status after differences in MMSE performance were partialed out. Thus, although the MMSE is useful in predicting dementia, there is an additional advantage of assessing specific indices of cognitive functioning. Further, supportive episodic memory tasks may be more salient predictors of incident AD than tasks that offer less supportive encoding or retrieval conditions.

Detection of mild dementia in community surveys. Is it possible to increase the accuracy of our diagnostic instruments?

OBJECTIVE: To investigate the accuracy of cognitive tests and clinical dementia diagnosis in distinguishing between mildly demented and nondemented subjects. DESIGN: Three-year longitudinal follow-up of a community-based cohort sample. Using the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised as criterion variable, subjects were classified as demented and nondemented based on the results of cognitive test performance at time 1. These subjects were then examined prospectively for development of dementia at time 2. PARTICIPANTS: The sample consisted of 63 mildly demented (Mini-Mental State Examination score > 18 < 24) and 398 nondemented subjects at time 1. At follow-up, due to death and refusal of participation, the sample consisted of 108 demented and 217 nondemented subjects. RESULTS: The group of subjects who were considered to be demented according to the results of the cognitive tests and nondemented by the clinical diagnosis at time 1 had a higher incidence of dementia at time 2 than did the subjects who were considered to be nondemented according to both cognitive tests and clinical diagnosis. Among the incident dementia cases, subjects considered to be demented according to the cognitive tests but nondemented by the clinical diagnosis performed at a lower level on most cognitive tests were older, had less education, and consisted of more women than did the group of subjects who were considered to be demented by the clinical diagnosis and nondemented by the cognitive tests at time 1. CONCLUSIONS: A combination of cognitive tests, especially tasks assessing episodic memory, can detect many subjects in a preclinical state of dementia who could be missed in the clinical diagnostic procedure due to subjects' relatively high age, low education, and female sex. However, cognitive tests also may miss a sizable proportion of prevalent dementia cases due to possible insensitivity to the same demographic variables. These findings indicate the need of integration between clinical and cognitive data to increase the accuracy in detecting dementia in an early phase.

Very old women at highest risk of dementia and Alzheimer's disease: incidence data from the Kungsholmen Project, Stockholm.

OBJECTIVE: To determine the incidence of different types of dementia in the very old, and to explore the relation with age and gender. DESIGN: A dementia-free cohort was followed for an average of three years in Stockholm, Sweden. At the end of the follow-up, the subjects were interviewed by nurses, clinically examined by physicians, and cognitively assessed by psychologists. Deceased cohort members were studied using death certificates, hospital clinical records, and discharge diagnoses. Dementia diagnoses were made according to the DSM-III-R criteria independently by two physicians. PARTICIPANTS: The cohort consisted of 1,473 subjects (75+ years old), of which 987 were clinically examined at follow-up, 314 died before the examination, and 172 refused to participate. RESULTS: During the follow-up, 148 subjects developed dementia. In the age-group 75 to 79, the incidence rates for dementia were 19.6 for women and 12.4 for men per 1,000 person-years, whereas for 90+ year-old subjects the corresponding figures were 86.7 and 15.0 per 1,000 person-years. A similar pattern of distribution by age and gender was seen for Alzheimer's disease. In each age stratum, the incidence rates of dementia and Alzheimer's disease were higher for women than for men. The age-adjusted odds ratio for women was 1.9 for dementia and 3.1 for Alzheimer's disease. CONCLUSIONS: (1) The incidence of dementia increases with age, even in the oldest age groups; (2) women have a higher risk of developing dementia than men, especially at very old ages; (3) this pattern is mainly due to the age and gender distribution of Alzheimer's disease, rather than vascular dementia.

Gender differences in episodic memory.

The relationship between gender and memory has been largely neglected by research, despite occasional studies reporting gender differences in episodic memory performance. The present study examined potential gender differences in episodic memory, semantic memory, primary memory, and priming. Five hundred thirty women and 470 men, randomly sampled from the city of Umeå, Sweden, 35-80 years of age, participated in the study. There were no differences between men and women with regard to age or education, or on a measure of global intellectual functioning. As has been demonstrated previously, men out performed women on a visuospatial task and women outperformed men on tests of verbal fluency. In addition, the results demonstrated that women consistently performed at a higher level than did men on the episodic memory tasks, although there were no differences between men and women on the tasks assessing semantic memory, primary memory, or priming. The women's higher level of performance on the episodic memory tasks could not be fully explained by their higher verbal ability.

Episodic memory deficit in elderly adults with suspected delusional disorder.

This study examined memory functions in two groups of elderly adults with and without suspected delusional disorder (SDD). The samples consisted of 66 normal elderly subjects and 33 elderly subjects with symptoms, as reported by close informants, of delusional disorder. Subjects were matched with regard to age, gender and education, and there were no differences between the two groups with regard to performance of visuo-spatial and primary memory tasks. Subjects were examined concerning a variety of episodic recall and recognition tasks. The results demonstrated that subjects with SDD performed at a lower level than controls for some episodic memory tasks (i.e. recall tasks). There were no group differences in measures of episodic recognition or in the primary memory tasks. In addition, the group of subjects with SDD was, to the same extent as the control group, able to utilize cognitive support in the form of organization, cues and previous knowledge in order to enhance episodic memory. In summary, it appears that elderly adults with SDD have a mild episodic memory deficit in the absence of other cognitive deficits.

Episodic memory and visuospatial ability in detecting and staging dementia in a community-based sample of very old adults.

BACKGROUND: This study examined the efficacy of a cognitive test battery in detecting and staging dementia in a community-based sample of very old adults. METHOD: The sample consisted of 398 nondemented and 108 demented adults taken from all the inhabitants in the Kungsholmen parish of Stockholm, Sweden (2,368 individuals), aged 75 years and older, who were part of a large-scale epidemiological study on aging and dementia. Participants received a cognitive test battery that consisted of specialized episodic memory tasks, as well as standardized psychometric measures of visuospatial ability and primary memory. RESULTS: A discriminant analysis revealed that highly supported episodic memory tasks (recognition, cued recall) were primarily responsible for correctly classifying normal old adults (94.5%) from those with the diagnosis of dementia (66.7%). Using the Mini-Mental State Exam (MMSE) as the criterion of dementia severity, a correct classification of 88.9% was achieved for mildly demented subjects and 77.8% for moderately demented subjects. Visuospatial tasks made the greatest contribution in distinguishing those at different levels of dementia severity. CONCLUSION: The results of this investigation indicate that cognitively supported measures assessing episodic memory may be particularly useful in the detection of dementia, whereas visuospatial measures are more effective in staging the disease. Consistent with biological models of the progression of dementia, this suggests that visuospatial abilities may deteriorate later and/or at a slower rate than episodic memory skills in the early stages of dementia. It is noteworthy that these conclusions are based on samples of very old adults taken from the general population.

Predicting episodic memory performance in dementia: is severity all there is?

Whether individual differences in demographic, psychometric, and biological domains can predict episodic memory in dementia was investigated. Mildly to moderately demented very old persons performed episodic memory tasks (free recall and recognition of slowly and rapidly presented random words, free and cued recall of organizable words, and recognition of dated and contemporary famous faces). A factor analysis of the memory measures yielded 2 factors, 1 indexing recall and 1 recognition. Controlling for severity of dementia, only 2 predictors contributed to performance: (a) Block Design (a marker of fluid intelligence) was positively related to recall, and (b) age was negatively related to recognition. Although these results are similar to data reported on predictors of episodic memory in normal aging, (a) the number of predictive variables appears to be reduced in dementia, and (b) age seems to affect recall and recognition differentially in normal aging and dementia.

Intracranial infusion of purified nerve growth factor to an Alzheimer patient: the first attempt of a possible future treatment strategy.

We report on the clinical outcome of a first case of intracranial infusion of nerve growth factor (NGF) to an Alzheimer patient. The therapeutic attempt is based on animal research showing that NGF stimulates central cholinergic neurons of the type known to be lost during the development of Alzheimer's disease (AD). Furthermore, our own previous clinical experience of infusing NGF to support the survival of intracranially transplanted adrenal chromaffin cells to Parkinsonian patients indicate this approach to be technically possible and safe and clinically of significant potential. Our first case was a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF over three months resulted in a marked transient increase in uptake and binding of [11C]nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF infusion, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects of the NGF infusion were found. The results of this single case indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.

Prior knowledge and face recognition in a community-based sample of healthy, very old adults.

This experiment addressed the effects of prior knowledge on episodic face recognition in a community-based sample of healthy older adults from 75 to 96 years of age (N = 228). Subjects were presented with photographs of public Swedish individuals who attained their fame during the 1930s and 1940s, or during the 1980s. Results indicated an overall deterioration of face recognition performance across age. However, performance was higher with the dated than with the contemporary faces across the entire age range, suggesting that the ability to utilize prior knowledge in the context of face recognition is well preserved in very old age. Finally, a multiple regression analysis indicated that, among a variety of demographic, psychometric, and biological variables, age was the best predictor of face recognition performance.

When Greta Garbo is easier to remember than Stefan Edberg: influences of prior knowledge on recognition memory in Alzheimer's disease.

This study investigated the effects of prior knowledge on recognition memory in patients with a mild Alzheimer's disease. Normal older adults and mildly demented patients were presented with dated and contemporary famous faces with name tags and were asked to generate unique statements about each person. Results indicated that both groups generated more statements about the dated than about the contemporary figures. Most important, both groups performed better with the dated than with the contemporary faces in an unexpected episodic face recognition task. This pattern of results suggests that both groups (a) possess more knowledge of dated than of contemporary famous individuals and (b) are able to utilize prior knowledge to enhance episodic remembering. Viewing these results in light of other recent work, it is concluded that differences between normal old and mildly demented individuals in the ability to utilize cognitive support for remembering may be differences in degree.

Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report).

Based on animal research suggesting that nerve growth factor (NGF) can stimulate central cholinergic neurons, the known losses of cholinergic innervation of the cortices in Alzheimer's disease (AD), and our experience of infusing NGF to support adrenal grafts in parkinsonian patients, we have initiated clinical trials of NGF infusions into the brain of patients with AD. Here we report a follow-up of our first case, a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF during three months resulted in a marked transient increase in uptake and binding of 11C-nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects could be ascribed to the NGF infusion. Taken together, the results of this case study indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.