A population-based study on brain atrophy and motor performance in elderly women.

BACKGROUND: Brain atrophy is a common neuroimaging finding in healthy elderly individuals as well as in patients with movement-related disorders. The relationship between brain atrophy and motor changes has not been frequently reported. This study investigates this relationship. METHODS: A population-based sample of women (N = 238), aged 70, 74, and 78 years, living in Göteborg, Sweden, participated in this study. Motor performance was measured by a laboratory test, the Postural-Locomotion-Manual test, which precisely measures the subject's mobility of lower and upper extremities using an optoelectronic technique. Cortical and central atrophy were rated on computerized tomographic (CT) scans of the brain. RESULTS: In bivariate analysis, temporal lobe atrophy, high sylvian fissure ratio, and high bicaudate ratio were correlated with impaired mobility. The association between temporal lobe atrophy and high sylvian fissure ratio and poor mobility remained after controlling for age, smoking, coronary heart disease, diabetes mellitus, hypertension, and white matter lesions on CT scans. CONCLUSIONS: Our results suggest that temporal lobe atrophy, which is often seen on brain imaging in elderly persons, might be an important brain abnormality related to motor impairments in elderly women. Further studies to investigate this relationship and its underlying mechanisms are needed.

A population-based study on blood pressure and brain atrophy in 85-year-olds.

In the general population, mean systolic and diastolic blood pressure increases up to age 75 years but decreases thereafter. The brain has a role in blood pressure regulation; it is not clear whether the cerebral changes that occur with aging contribute to the decline in blood pressure in the very elderly. We examined a population-based sample of 484 85-year-old persons (344 nondemented and 140 demented, 61 with Alzheimer's disease, 65 with vascular dementia, and 14 with other types of dementia) with a neuropsychiatric examination and blood pressure measurements. Dementia was diagnosed according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders, edition 3, revised. Brain atrophy was measured by CT of the brain. In the nondemented group, frontal (r=-0.18, P=0.037) and parietal (r=-0.23, P=0.008) cortical atrophy and bifrontal ratio (r=-0.20, P=0.013) were associated with lower systolic blood pressure, and frontal (r=-0.23, P=0.010) and parietal (r=-0.24, P=0.008) cortical atrophy and bifrontal ratio (r=-0.23, P=0.006) with lower diastolic blood pressure. Systolic blood pressure was lower in subjects with Alzheimer's disease and vascular dementia, and diastolic blood pressure was lower in those with vascular dementia compared with the nondemented. Systolic (r=-0.27, P<0.0001) and diastolic (r=-0.10, P=0.020) blood pressure was negatively correlated to dementia severity. In the demented subjects, frontal cortical atrophy was correlated to lower diastolic blood pressure (r=-0.21, P=0.043). Our findings suggest that age-related changes in brain structure may contribute to the decrease in blood pressure in the very elderly and that low blood pressure in dementia disorders is mainly a secondary phenomenon.

Apolipoprotein E in cerebrospinal fluid in 85-year-old subjects. Relation to dementia, apolipoprotein E polymorphism, cerebral atrophy, and white matter lesions.

OBJECTIVE: To further elucidate the pathogenetic role of apolipoprotein E (Apo E) in degenerative brain disorders, we analyzed cerebrospinal fluid (CSF) levels of Apo E in 85-year-old subjects with dementia disorders. DESIGN: Survey. SETTING: Community. PARTICIPANTS: Population-based sample of 27 demented (12 with Alzheimer disease [AD]; 13, vascular dementia [VAD]; and 2, other types of dementia) and 35 nondemented individuals. MAIN OUTCOME MEASURES: Cerebrospinal fluid levels of Apo E, Apo E polymorphism, and brain atrophy and white matter lesions (WMLs) measured by computed tomography (CT) of the brain. Dementia was defined according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria; AD, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria; and VAD, National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neuroscience criteria. RESULTS: The mean (+/- SD) CSF levels of Apo E were lower in the AD (2.6 +/- 1.5 mg/L; P < .02) and VAD groups (2.5 +/- 0.9 mg/L; P < .002) than in the nondemented group (3.8 +/- 1.7 mg/L). Cerebrospinal fluid levels of Apo E decreased with increasing severity of dementia and with increasing temporal cortical and central frontal atrophy. In nondemented individuals, CSF levels of Apo E decreased with increasing degree of WMLs. Cerebrospinal fluid levels of Apo E were not influenced by the Apo E4 isoform. CONCLUSIONS: Whether our finding of an association between low CSF levels of Apo E and dementia disorders (both degenerative, such as AD, and vascular, such as VAD) is related to the pathogenesis of these disorders or is a secondary consequence of the disease process remains to be established. Although statistical correlations do not give direct evidence of causal relations, the correlations between CSF level of Apo E and severity of dementia and cortical atrophy suggest that CSF level of Apo E follows the disease process.

15-year longitudinal study of blood pressure and dementia.

BACKGROUND: Vascular causes of dementia may be more common than supposed. Vascular factors may also have a role in late-onset Alzheimer's disease, but the role of hypertension in the development of dementia is unclear. METHODS: As part of the Longitudinal Population Study of 70-year-olds in Göteborg, Sweden, we analysed the relation between blood pressure and the development of dementia in the age intervals 70-75, 75-79, and 79-85 years in those non-demented at age 70 (n = 382). The sample was followed up for 15 years and examined repeatedly with a comprehensive investigation, including a psychiatric and physical examination. a FINDINGS: Participants who developed dementia at age 79-85 had higher systolic blood pressure at age 70 (mean 178 vs 164 mm Hg, p = 0.034) and higher diastolic blood pressure at ages 70 (101 vs 92, p = 0.004) and 75 (97 vs 90, p = 0.022) than those who did not develop dementia. For subtypes of dementia, higher diastolic blood pressure was recorded at age 70 (101, p = 0.019) for those developing Alzheimer's disease and at age 75 (101, p = 0.015) for those developing vascular dementia than for those who did not develop dementia. Participants with white-matter lesions on computed tomography at age 85 had higher blood pressure at age 70 than those without such lesions. Blood pressure declined in the years before dementia onset and was then similar to or lower than that in non-demented individuals. INTERPRETATION: Previously increased blood pressure may increase the risk for dementia by inducing small-vessel disease and white-matter lesions. To what extent the decline in blood pressure before dementia onset is a consequence or a cause of the brain disease remains to be elucidated.

The influence of white matter lesions on neuropsychological functioning in demented and non-demented 85-year-olds.

White matter lesions on computed tomography of the head were studied in relation to neuropsychological functioning in subjects from a representative sample of non-demented (n = 134) and demented (n = 98) 85-year-olds. Non-demented subjects with white matter lesions (n = 46) scored significantly lower in tests of verbal ability (Synonyms), spatial ability (Block Design, Clock Test), perceptual speed (Identical forms), secondary memory (Thurstone Picture Memory), basic arithmetic (Coin Test) and the global cognitive screening test Mini-Mental State Examination than non-demented subjects without white matter lesions (n = 88). Demented subjects with white matter lesions (n = 67) scored significantly lower in tests of spatial ability (Block Design and Clock Test) and secondary memory (free recall in the MIR memory test, Ten-word memory test I and II) and in the Mini-Mental State Examination than demented subjects without white matter lesions (n = 31). It is concluded that white matter lesions contribute to cognitive decline in both non-demented and demented elderly subjects.

A population-based study of tau protein and ubiquitin in cerebrospinal fluid in 85-year-olds: relation to severity of dementia and cerebral atrophy, but not to the apolipoprotein E4 allele.

Alzheimer's disease (AD) is the most common form of dementia, and is characterized by a degeneration of neurones and their synapses, and a higher number of senile plaques (SP) and neurofibrillary tangles (NFT) compared with that found in non-demented individuals of the same age. NFT are composed of a hyperphosphorylated and ubiquitinated form of tau protein. Previous studies have found that in the cerebrospinal fluid (CSF) both tau and ubiquitin are increased in AD. We examined CSF-tau and CSF-ubiquitin in a population based sample of 85-year-olds, 26 demented (11 with probable Alzheimer's disease (AD), 13 with probable vascular dementia (VAD) and 2 with mixed (AD/VAD) type of dementia) and 35 non-demented individuals. CSF-tau was significantly higher both in the probable AD group (254 +/- 113 pg/mL; P < 0.01), and in the probable VAD group (247 +/- 75 pg/mL; P < 0.005), than in the non-demented group (171 +/- 78 pg/mL), but did not significantly differ between the probable AD and probable VAD groups. In contrast, CSF-ubiquitin did not significantly differ between the probable AD (100 +/- 24 ng/mL), probable VAD (102 +/- 16 ng/mL), and non-demented (97 +/- 27 ng/mL) groups. CSF-tau increased with increasing severity of dementia (P < 0.001), though no such relation was found for CSF-ubiquitin. Neither CSF-tau nor CSF-ubiquitin differed between patients with or without the apolipoprotein E E4 isoform. Higher CSF-tau and CSF-ubiquitin levels were also associated with increasing degree of cortical and central brain atrophy as measured by computerized tomography. The relationships between CSF-tau and severity of dementia and to brain atrophy suggest that CSF-tau may be used as a measure of neuronal/axonal degeneration in patients with dementia. We have previously shown a marked increase in both CSF-tau and CSF-ubiquitin in younger patients with AD and VAD. The less pronounced increase in CSF-tau and the lack of difference in CSF-ubiquitin in older patients suggest that the severity of the degenerative process is less in older than in younger demented patients.

The prevalence of white-matter lesions on computed tomography of the brain in demented and nondemented 85-year-olds.

The prevalence of white-matter lesions on computed tomography was studied in a representative sample of 85-year-olds living in Gothenburg, Sweden. The study included a psychiatric examination, interview of a close informant, neuropsychological examination, physical examination, comprehensive laboratory tests, electrocardiogram, chest x-ray, computed tomography scan of the head, and cerebrospinal fluid analysis. The diagnoses of dementia and other mental disorders were made according to DSM-III-R criteria. The prevalence of white-matter lesions in demented subjects was 68.9%, and in nondemented, 33.8%. Their prevalence was not increased in any mental disorder other than dementia. All severities of dementia and the subtypes, Alzheimer's disease, vascular dementia, and other types of dementia, had a significantly higher prevalence of white-matter lesions than did nondemented subjects. The risk for dementia, but not its severity, increased with the severity of these lesions. A stepwise logistic regression analysis showed that both white-matter lesions and infarcts on computed tomography contributed independently to dementia. White-matter changes may be a contributing cause of dementia in the oldest old, or may represent a disease entity of its own. They are important to recognize since they may be potentially preventable, or even treatable.

A population-based study of dementia in 85-year-olds.

BACKGROUND: The aim of this study was to investigate the causes, severity, and prevalence of dementia in a representative sample of 494 85-year-olds living in Gothenburg, Sweden. METHODS: The study included a psychiatric interview, neuropsychological and physical examinations, comprehensive laboratory tests, electrocardiography, chest radiography, computed tomography (CT) of the head, and analysis of cerebrospinal fluid. A person close to each subject was also interviewed. Dementia was defined according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised), Alzheimer's disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and vascular dementia according to recently proposed criteria that incorporate information from CT scanning and the patient's neurologic history. RESULTS: The prevalence of dementia was 29.8 percent (147 subjects). The condition was mild in 8.3 percent, moderate in 10.3 percent, and severe in 11.1 percent. There were no significant sex-related differences in prevalence or severity. Of the subjects with dementia, 43.5 percent had Alzheimer's disease, 46.9 percent had vascular dementia (multi-infarct dementia in 34.6 percent, dementia related to cerebral hypoperfusion in 4.1 percent, and mixed dementia in 8.2 percent), and 9.5 percent had dementia due to other causes. The three-year mortality rate was 23.1 percent in the subjects without dementia, 42.2 percent in the patients with Alzheimer's disease, and 66.7 percent in the patients with vascular dementia. Infarcts detected by CT scanning were significantly more common in the subjects with dementia than in those without it (27.9 percent vs. 12.6 percent). CONCLUSIONS: Dementia was present in nearly a third of unselected 85-year-olds in Sweden. Almost half these subjects appeared to have vascular dementia, which may currently be more amenable to prevention or treatment than Alzheimer's disease.