Apolipoprotein E, cognitive function, and dementia in a general population aged 85 years and over

We examined 510 subjects representing 83.2% of all citizens of a Finnish city aged 85 years or over. Mini-Mental State Examination (MMSE) scores, diagnosis of dementia by DSM-III-R criteria, and Apo-E genotype were determined. The prevalence of dementia was 38.6%. The odds ratio (OR) of the Apo-E epsilon4 carriers (with the reference population of people with the genotype epsilon3/epsilon3) for dementia was 2.36 (95% CI 1.58 - 3.53). There was a significant sex difference: The OR in women was 3.23 (95% CI 2.02 - 5.17) whereas among men it was insignificant. The mean MMSE score (+/- SD) among the Apo-E epsilon4 carriers (15.0 +/- 10.0) and noncarriers (18.7 8.6) (p < .001) differed among the whole population, but not within the demented or nondemented subjects analyzed separately. This study does not support the hypothesis that the Apo-E epsilon4 allele impairs cognitive functions of nondemented elderly, at least in those surviving to very old age.     

Cognitive impairment and dementia 20 months after stroke

BACKGROUND AND PURPOSE: Dementia is common after stroke, but the dementia syndrome does not cover the whole spectrum of cognitive impairment. Our aim was to quantify and compare dementia and cognitive impairments in elderly patients 1.5 years after stroke and a matched normal population. SUBJECTS AND METHODS: We examined dementia and cognitive impairments in 149 out of an initial total of 243 acute stroke patients after a mean 20 months. Inclusion criteria were age > or =70 years, not living in an institution and no previous cerebral lesion. The patients' mean age was 81 years. Five controls matched by age and gender and fulfilling the same exclusion criteria were selected for each patient (n = 745) from a population-based survey in the same area. Dementia was diagnosed according to the DSM-III-R criteria, and impairments in different dimensions of cognitive function were assessed. RESULTS: The prevalence of dementia was 28% in the stroke patients and 7.4% in the controls (OR 4.7; 95% CI 3.0-7.5). Seventy-two percent of the patients had cognitive impairments compared to 36% in the controls. Cognitive impairments were more common in nondemented stroke patients than in nondemented controls: 61 vs. 31% (OR 3.5; 95% CI 2.3-5.3). The risk increase attributable to stroke was highest for patients below 80 years of age. CONCLUSIONS: Stroke confers an increased risk of dementia and cognitive impairments in the elderly, especially in the younger ones. Apraxia is the most frequent neuropsychiatric impairment after stroke. The concept of dementia does not describe cognitive impairments well, since it underestimates their extent not only after stroke but also in normal ageing.     

Psychotic symptoms and paranoid ideation in a nondemented population-based sample of the very old.

BACKGROUND: Psychotic symptoms are reported to be uncommon in the elderly, and may be underrated in traditional epidemiological studies. METHODS: Psychotic symptoms, physical disorders, disability in daily life, and sensory impairments were assessed using results of psychiatric and physical examinations, key-informant interviews, and medical record reviews in a representative sample of nondemented individuals aged 85 years living in the community or in institutions in G?teborg, Sweden (n = 347). The sample was observed for 3 years regarding psychotic symptoms, mortality, and incident dementia. RESULTS: The prevalence of any psychotic symptom was 10.1% (95% confidence interval [CI], 7.1%-13.7%); hallucinations, 6.9% (95% CI, 4.5%-10.1%); and delusions, 5.5% (95% CI, 3.3%-8.4%). The prevalence of paranoid ideation was 6.9% (95% CI, 4.5%-10.1%). Stepwise logistic regression analyses showed that hallucinations were associated with major depressive syndrome (odds ratio [OR], 3.9; 95% CI, 1.3-11.9), disability in daily life (OR, 5.2; 95% CI, 1.8-14.9), and visual deficits (OR, 3.4; 95% CI, 1.0-11.1). Delusions were associated with disability in daily life (OR, 4.9; 95% CI, 1.8-13.3). Paranoid ideation was associated with visual deficits (OR, 3.6; 95% CI, 1.2-10.5) and myocardial infarction (OR, 4.6; 95% CI, 1.7-12.6). Hallucinations (OR, 3.1; 95% CI, 1.4-6.8), delusions (OR, 2.9; 95% CI, 1.2-6.9), and paranoid ideation (OR, 2.7; 95% CI, 1.2-6.2) were each related to increased incidence of dementia from 85 to 88 years of age. Hallucinations and paranoid ideation were associated with increased 3-year mortality in women but not in men. CONCLUSIONS: We found a higher prevalence of psychotic symptoms and paranoid ideation in the elderly than previously reported, and these symptoms were associated with a poor prognosis.     

Risk of dementia in Parkinson's disease: a community-based, prospective study

OBJECTIVE: To calculate the incidence of and determine possible risk factors for dementia in PD. BACKGROUND: Dementia has important clinical consequences for patients with PD and their caregivers, but the incidence is unknown. METHODS: A population-based cohort of nondemented patients with PD (n = 171) from the county of Rogaland, Norway, was assessed at baseline and 4.2 years later with a comprehensive evaluation of motor, cognitive, and neuropsychiatric symptoms. The diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) criteria, based on interview of the patient and a caregiver, cognitive rating scales, and neuropsychologic tests. A representative sample of 3,062 nondemented elderly subjects without PD served as control group. RESULTS: Forty-three patients with PD were demented at follow-up evaluation, equivalent to an incidence rate of 95.3 per 1,000 person-years (95% CI, 68.2 to 122.0). The risk for the development of dementia in patients with PD relative to the control subjects after adjusting for age, sex, and education was 5.9 (95% CI, 3.9 to 9.1). Predictive factors at baseline for dementia in PD in addition to age were Hoehn & Yahr score >2 (OR, 3.4; 95% CI, 1.3 to 8.6) and Mini-Mental State Examination score < 29 (OR, 3.3; 95% CI, 1.3 to 8.2). CONCLUSIONS: Patients with PD have an almost sixfold increased risk for becoming demented compared with subjects without PD.     

Risk of Alzheimer's disease in relatives of Parkinson's disease patients with and without dementia

OBJECTIVE: To determine whether first-degree relatives of PD patients with dementia were at increased risk for the development of AD compared with first-degree relatives of nondemented PD patients and nondemented normal subjects from the community. METHODS: A structured family history interview was administered to 146 nondemented PD patients, 120 patients with PD and dementia, and 903 normal subjects from the community to ascertain the presence of AD among parents and siblings of these subjects. Cox proportional hazards models with double censoring techniques for missing information were used to model the risk of AD among relatives. RESULTS: No increase in risk of AD was found among parents of patients with PD and dementia or parents of nondemented PD patients compared with parents of normal subjects. However, siblings of demented PD patients were three times as likely (relative risk [RR] = 3.2, 95% confidence interval [CI] = 1.1 to 9.4, p < 0.04) as siblings of normal subjects to develop AD. When only siblings >65 years of age were considered, there was a fivefold increase in risk of AD among siblings of demented PD patients compared with siblings of normal subjects (RR = 4.9, 95% CI = 1.1 to 21.4, p < 0.03). The risk of AD was also increased for female relatives, regardless of whether the woman was a relative of a demented PD patient, a nondemented PD patient, or a normal subject. Ethnicity and APOE genotype did not affect dementia status among relatives. CONCLUSIONS: The increased risk of AD in siblings of demented PD patients compared with siblings of normal subjects supports the possibility of familial aggregation of AD and PD with dementia.     

APOE epsilon4 does not predict mortality, cognitive decline, or dementia in the oldest old

OBJECTIVE: To examine the effect of the epsilon 4 allele on cognitive decline in the oldest old. METHODS: We studied all 601 citizens of the city of Vantaa age 85 years and older in 1991. A total of 553 subjects (92%) took part in the study, which used the Mini-Mental State Examination (MMSE) and assessment of dementia according to the Diagnostic and Statistical Manual of Mental Disorders, third ed., revised (DSM-III-R) criteria. The survivors were re-examined 3 years later. APOE genotype was determined in 510 subjects, representing 83.2% of the original population. RESULTS: Approximately one-half of the subjects (n = 250) died before the follow-up, and 253 subjects (97.3% of the survivors) were re-examined. The occurrence of the APOE epsilon 4 allele did not have any significant effect on survival. Of the 187 previously nondemented subjects, 58 (31%) had developed dementia. The OR for the epsilon 4 carriers to develop dementia was not significant: OR = 1.78; 95% CI = 0.88 to 3.60. In individuals with a follow-up MMSE score (n = 222), the mean decline in the score was 3.1 points. APOE epsilon 4 carrier status did not have a significant effect on the mean MMSE change except in the previously demented subjects, among whom the drop was larger in the APOE epsilon 4 carriers. CONCLUSIONS: The lack of association between APOE epsilon 4 carrier status and mortality, or development of dementia, or cognitive decline in these very elderly people, whether analyzed in the whole population or among the nondemented subjects only, suggests that the APOE epsilon 4 effect in younger subjects is age-dependent, and that it is no longer present in very old age.     

Incidence of dementia in very elderly individuals: a clinical, neuropathological and molecular genetic study

AIMS: To evaluate the effect of medical record use on figures for the incidence of dementia and the effect of apolipoprotein E (APOE) polymorphism on this incidence and neuropathologically defined Alzheimer's disease (AD) in very elderly individuals. METHODS: Cognitive functions were examined in a cohort of 328 (92% of the very elderly people of a town participated in this study) nondemented Finnish elderly individuals 85 years of age or more in 1991. The examination was repeated in survivors in 1994, 1996, 1999 and 2001. Medical notes and social work records were evaluated. All these individuals were genotyped for APOE. Neuropathological analysis of AD-type pathology was performed on 159 of 303 subjects who died during the follow-up. RESULTS: Age group, gender or APOE did not significantly affect the incidence of dementia, which was over 20% higher (85 vs. 69 per 1,000 person-years) if the cognitive status at death was ascertained by medical and social work records than without this evaluation. The APOE upsilon4 allele was highly significantly (p=0.002) and age almost significantly (p=0.06) associated with neuropathological AD in nondemented individuals. CONCLUSIONS: Medical records should be analyzed in studies on the incidence of dementia in very elderly individuals. APOE polymorphism does not affect the incidence of dementia in this age group. However, clinical dementia diagnosis in very elderly individuals does not necessarily correlate well with the presence of neuropathological AD which, even in this age group, is significantly associated with the APOE upsilon4 allele.     

Memory impairment on free and cued selective reminding predicts dementia

OBJECTIVE: To estimate the relative rates of dementia in initially nondemented subjects with and without memory impairment defined by baseline free recall from the Free and Cued Selective Reminding (FCSR) test. BACKGROUND: Our approach to identifying persons at high risk for future dementia is to show the presence of memory impairment not caused by other cognitive deficits by using a memory test that controls attention and cognitive processing. When the conditions of testing are not adequately controlled, prediction is reduced because age-associated memory deficits due to other cognitive deficits are confused with dementia-associated memory deficits. METHODS: Longitudinal evaluation of 264 initially nondemented, elderly community volunteers from the Einstein Aging Study with clinical and psychometric examinations every 12 to 18 months for up to 10 years. MAIN OUTCOME MEASURES: Dementia was defined by an algorithmic definition that required a Blessed Information Memory and Concentration score >8 and clinical evidence of functional decline. RESULTS: Thirty-two incident cases of dementia developed during follow-up. Survival analyses indicated that subjects with impaired free recall at baseline had dementia develop (relative risk = 75.2, 95% CI = 9.9 to 567) over 5 years of follow-up at dramatically higher rates than subjects with intact free recall after adjusting for age, gender, and education. CONCLUSION: Poor performance on free recall from FCSR predicts future dementia. These findings support the existence of a preclinical phase of dementia characterized by memory impairment, which is present for at least 5 years before diagnosis.     

A community-based study of survival in dementia.

The objective of this study was to compare the mortality rate of demented and nondemented subjects in a single cohort. We followed up a cohort of subjects comprising all 1259 inhabitants of Leiden aged 85 years and over, evaluated earlier for the presence of dementia, and including institutionalized subjects. The main outcome measure was the mortality rate ratio of the demented and nondemented groups adjusted for age and sex. The mortality rate ratio of the demented vs the nondemented group was 1.9 (95% confidence interval: 1.7-2.2). No difference in mortality rate was found between those with mild vs moderate to severe dementia. The mortality rate in dementia patients is higher than in nondemented subjects.     

Diagnosis of dementia in a heterogeneous population. Development of a neuropsychological paradigm-based diagnosis of dementia and quantified correction for the effects of education.

A brief diagnostic battery of neuropsychological tests was developed for a large-scale epidemiological study of dementia. We operationally defined dementia as defective memory and defective performance in at least two other areas, including orientation, abstract reasoning, construction, and language. Criterion scores for defining defective performance on each test were developed. In a pilot study that used 51 different subjects with a working diagnosis based on physicians' assessment (ie, 32 demented and 29 nondemented subjects), the test-based diagnosis agreed with the working diagnosis in all but two cases. The test battery was then applied to 430 healthy elderly subjects. Eighteen percent of those with 8 or less years of education met criteria for dementia compared with 5% of those with more than 8 years of education. We computed education-corrected scores for each test with the use of residuals from the regression of each test score on education. Based on corrected scores, 12 subjects were reclassified as nondemented and 11 as demented. Subjects who were reclassified as demented were significantly more impaired in activities of daily living than nondemented subjects who were not reclassified. Activities of daily living in subjects who were reclassified as nondemented did not differ from those in demented subjects who were not reclassified. These findings suggest that the neuropsychological battery may have utility in the diagnosis of dementia. However, neuropsychological performance may be influenced by education, and some form of adjustment, such as correction for activities of daily living, may be required in epidemiological studies.     

Use of psychotropics among home-dwelling nondemented and demented elderly

OBJECTIVE: To describe the use of psychotropics in the nondemented and demented elderly. PARTICIPANTS: The home-dwelling elderly (n=523) among the random sample of 700 subjects from the total population of individuals aged 75 years or more in 1998 and living in the city of Kuopio, Finland. METHODS: A trained nurse interviewed the participants about their health and current use of medicines. A geriatrician performed clinical examinations and diagnosed diseases. Dementia and depression were diagnosed according to the DSM-IV criteria. RESULTS: The demented subjects used more medicines of all kinds (p<0.01), and especially more psychotropics than the nondemented (p<0.001). One in four demented subjects, compared to one in ten nondemented ones used at least two psychotropics (p<0.01). The demented subjects used antipsychotics six times more often than the nondemented ones (p<0.001). Among the nondemented subjects, one out of two antipsychotics users was suffering from depression according to DSM-IV criteria. Three out of four persons who had dementia with Lewy bodies were using psychotropics. Persons with moderate dementia were more commonly using all kinds of psychotropic preparations especially, antipsychotics three times more commonly than persons with mild or severe dementia. CONCLUSION: Psychotropics, especially antipsychotics, are commonly used in the treatment of both nondemented and demented elderly, even without proper indication. Physicians need more training about the appropriate use of psychotropics to minimize their adverse effects.     

Influence of leisure activity on the incidence of Alzheimer's disease.

OBJECTIVE: To determine whether leisure activities modify the risk for incident dementia. BACKGROUND: Although high educational and occupational attainments have been associated with reduced risk of incident dementia, the relation between leisure activities and dementia risk has not been adequately investigated. METHODS: A total of 1,772 nondemented individuals aged 65 years or older, living in northern Manhattan, New York, were identified and followed longitudinally in a community-based cohort incidence study. Subjects' leisure activities at baseline were assessed, annual examinations with the same standardized neurologic and neuropsychological measures were performed for up to 7 years (mean 2.9 years), and incident dementia was assessed as the main outcome measure. Cox proportional hazards models, adjusting for age, ethnic group, education, and occupation, were used to estimate the relative risk (RR) of incident dementia associated with high leisure activities. RESULTS: Of the 1,772 subjects, 207 became demented. The risk of dementia was decreased in subjects with high leisure activities (RR, 0.62; 95% CI 0.46 to 0.83). The association of high leisure with decreased RR of incident dementia was present even when baseline cognitive performance, health limitations interfering with desired leisure activities, cerebrovascular disease, and depression were considered. CONCLUSIONS: The data suggest that engagement in leisure activities may reduce the risk of incident dementia, possibly by providing a reserve that delays the onset of clinical manifestations of the disease.     

Metabolic syndrome and dementia risk in a multiethnic elderly cohort

BACKGROUND/AIMS: The metabolic syndrome (MeSy) may be related to Alzheimer's disease (AD). Our aims were to investigate the association of the MeSy with incident dementia in a multiethnic elderly cohort in the United States. METHODS: We conducted cross-sectional and prospective analyses in 2,476 men and women aged 65 years and older and with data available on the MeSy and dementia diagnosis in Northern New York City. MeSy was defined by the National Cholesterol Education Program Adult Treatment Program III and the European Group for the Study of Insulin Resistance criteria. Dementia was diagnosed using standard criteria. RESULTS: No association was found between MeSy and prevalent dementia. After 4.4 years of follow-up, 236 individuals of the 1,833 without prevalent dementia developed dementia. MeSy was not associated with incident dementia. Of the components of the MeSy, diabetes and hyperinsulinemia were associated with an increased risk of incident AD [hazard ratio 1.4 (95% CI 1.0-2.1), and hazard ratio 1.4 (95% CI 0.9-2.7), respectively] and dementia associated with stroke [hazard ratio 1.9 (95% CI 1.1-3.1), and hazard ratio 2.3 (95% CI 1.1-4.7), respectively]. CONCLUSIONS: The MeSy was not associated with an increased dementia risk in a multiethnic elderly cohort, but diabetes and hyperinsulinemia were. In the elderly, examining diabetes and hyperinsulinemia separately may be preferable to using the MeSy as a risk factor.     

Significant association of metabolic syndrome with silent brain infarction in elderly people

A silent brain infarction (SBI) can predict clinical overt stroke or dementia. Studies focusing on the elderly population, where SBI is most common, are sparse. We examined the associations between SBI and metabolic syndrome (MetS) in healthy elderly individuals. Neurologically healthy subjects (1,254 persons, 723 males) aged ≥65 years who underwent brain MRI were evaluated. MetS was diagnosed following the AHA/NHLBI-2005 criteria. We examined associations between full syndrome (at least three of the five conditions) as well as its components and SBI while controlling for possible confounders. One hundred and ninety-seven subjects (15.7%) were found to have one or more SBIs on MRI. Age (1-year difference) was found to be significantly related to SBI prevalence (OR 1.09; 95% CI 1.05–1.12). MetS was significantly associated with SBI (OR 1.68; 95% CI 1.15–2.44). The component model of MetS showed a strong significance between elevated blood pressure (OR 1.89; 95% CI 1.23–2.91) and SBI. Subjects exhibiting more components of MetS showed more prevalent SBI and multiple SBIs. MetS was found to be significantly associated with SBI in neurologically healthy elderly people. The positive trend between the number of MetS components and SBI could be used as a diagnostic tool to predict and prevent future stroke.     

Homocysteine and cognitive function in the elderly: the Rotterdam Scan Study

BACKGROUND: Elevated plasma total homocysteine (tHcy) concentrations are associated with AD and vascular dementia, but the relation with cognitive performance in nondemented elderly people is not known. OBJECTIVE: To examine the association of tHcy and cognitive function in the elderly, and assess whether this may be mediated by structural brain changes on MRI. METHODS: The Rotterdam Scan Study is a population-based study of 1,077 nondemented elderly. Cognitive performance was assessed, and compound scores were constructed for psychomotor speed, memory function, and global cognitive function. Cerebral infarcts, white matter lesions, and generalized brain atrophy were measured on MRI. The cross-sectional relationship between tHcy levels and neuropsychological test scores was assessed by multiple regression. RESULTS: Mean tHcy level was 11.5 micro mol/L (SD 4.1). Increasing tHcy levels were associated with lower scores for psychomotor speed, memory function, and global cognitive function, and this was largely due to the association with tHcy levels in the upper quintile (>14 micro mol/L). Adjusted differences between test scores of participants in the upper quintile as compared with the lower four quintiles of tHcy were -0.26 (95% CI: -0.37; -0.14) for psychomotor speed, -0.13 (95% CI: -0.27; 0.01) for memory function, and -0.20 (95% CI: -0.30; -0.11) for global cognitive function. These associations were not mediated by structural brain changes on MRI. CONCLUSION: Elevated tHcy levels are associated with decreased cognitive performance in nondemented elderly people, and the relation was most marked for psychomotor speed. This association was independent of structural brain changes on MRI.     

Different classification systems yield different dementia occurrence among nonagenarians and centenarians

Literature data consistently show different prevalence estimates of dementia when different classification systems are used in the same population. Very few data are available for the oldest old of the elderly. We investigated the occurrence of dementia among 34 nonagenarians and centenarians according to four classification systems: the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, third edition revised (DSM-III-R) and fourth edition (DSM-IV), the World Health Organization's International Classification of Diseases, 10th revision (ICD-10), and the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). Cognitive functioning, work, social function and independence in activities of daily living were evaluated by using an extensive neuropsychological examination. The prevalence (95% CI) of dementia was the following: 47.1% (95% CI 30.3-63.8) with the DSM-III-R criteria, 41.2% (95% CI 24.6-57.7) with the DSM-IV criteria, 29.4% (95% CI 14.1-44.7) with the ICD-10 criteria and 38.2% (95% CI 21.9-54.6) with the CAMDEX. The factors that best predicted disagreement between DSM-III-R and DSM-IV were calculation impairment and the presence or absence of personality changes. DSM-III-R and ICD-10 were differentiated by the weight given to executive functions that all have to be impaired according to ICD-10, whereas progressive deterioration differentiated CAMDEX from DSM-III-R. It should be noted that although the DSM-III-R diagnoses differ by a factor of 1.6 times from the ICD-10 and 1.2 times from the CAMDEX diagnoses, we are speaking about dementia, which is very frequent in nonagenarians and centenarians. Moreover, with regard to public health, an estimation of the number of subjects who will lose their autonomy is rather more useful and informative than simple prevalence figures of dementia by itself. In this light, classification systems, such as the ICD-10, that do not include impairment of social function as a criterion for assessing dementia become less adequate.     

APOE and the risk of PD with or without dementia in a population-based study

OBJECTIVE: To study the association between APOE genotype and PD with or without dementia. METHODS: The study formed part of the Rotterdam Study, a prospective, population-based cohort study on the frequency, etiology, and prognosis of chronic diseases. The cohort examined for PD consisted of 6,969 independently living or institutionalized inhabitants from a suburb of Rotterdam, the Netherlands, aged 55 years or older. All participants were screened at baseline (1990 to 1993) and at follow-up (1993 to 1994) for symptoms of parkinsonism by study physicians; screen positives received a diagnostic workup by a neurologist. RESULTS: APOE genotyping was available for 107 PD patients (26 with and 81 without dementia) and 4,805 non-PD control subjects. The presence of at least one epsilon2 allele significantly increased the risk of PD (OR = 1.7; 95% CI, 1.0 to 2.8). When we looked separately for demented and nondemented PD patients as compared with nonparkinsonian controls, APOE did not appear to be associated with PD without dementia, but both the epsilon2 and the epsilon4 allele increased the risk of PD with dementia (OR = 5.6; 95% CI, 2.0 to 15.2 and OR = 3.6; 95% CI, 1.3 to 9.9). The risk of dementia for epsilon4 allele carriers was not significantly different for persons with or without PD. However, the epsilon2 allele strongly increased the risk of dementia in patients with PD (interaction p < 0.007). CONCLUSIONS: In the elderly the APOE-epsilon2 allele increases the risk of PD and, in particular, the risk of PD with dementia.     

Quantitative MRI findings and cognitive impairment among community dwelling elderly subjects

OBJECTIVES: To study the factors which influence cognitive impairment among elderly subjects living in a local community, based on both MRI and clinical findings, to further elucidate the causes of dementia, and also to help develop strategies for its prevention. METHODS: Cranial MRI and other medical examinations were performed on non-demented elderly subjects who resided in one rural community. A total of 254 subjects aged from 60 to 91 years of age, with a mean age of 73.9 (SD 6.8) were examined. The mini mental state examination (MMSE) was used to identify cognitive impairment. White matter lesions and cerebral atrophy on MR images were measured quantitatively. A multivariate analysis was also performed with the existence of cognitive impairment as the dependent variable, and the MRI findings and clinical observations were used as the independent variables. RESULTS: Cognitive impairment was present in 46 subjects (18.1%). They were older, had a lower educational level, and more frequent hypertension compared with those without cognitive impairment. The packed cell volume was lower in the impaired group. In addition, their MRI findings showed significantly larger quantities of white matter lesions and cerebral atrophy, as well as more infarcts. A logistic regression analysis demonstrated a significant relation among such factors as white matter lesions (odds ratio (OR) 1.575, 95% confidence interval (95% CI) 1.123-2.208), cerebral atrophy (OR 0.761, 95%CI 0.587-0.987), and lower education (OR 0.682, 95%CI 0.544-0.855) for subjects with a cognitive impairment. CONCLUSIONS: White matter lesions and cerebral atrophy are factors which induce a cognitive impairment in community dwelling elderly subjects without dementia. It is important to carefully watch for any abnormalities in these factors, and to perform cohort studies to check for the above risk factors, to both prevent and make an early diagnosis of dementia.     

Occurrence of cognitive impairment and dementia after the age of 60: a population-based study from Northern Italy

OBJECTIVE: To evaluate the age, gender and education distribution of both cognitive impairment and dementia in the whole old age range of the elderly (from 61 years of age and over). SUBJECTS AND METHODS: The study population consisted of all subjects born in 1930 or before, living in the municipality of Faenza and Granarolo, Italy (n = 7,930). A two-phase study design was implemented, by using the Mini-Mental State Examination and Global Deterioration Scale as screening instruments. The DSM-III-R diagnostic criteria were used for the clinical diagnosis of dementia. A subject was classified as affected by cognitive impairment, no dementia (CIND) if he/she scored 2 or more standard deviations lower than the corrected mean MMSE score. RESULTS: The prevalences of dementia and CIND were 6.5 per 100 (95% CI 5.9-7.0) and 5.1 per 100 (95% CI 4.6-5.6), respectively. The prevalence of CIND was higher than that of dementia in the youngest old groups (61-74 years), both in men and women, whereas the opposite pattern was present among the older old (75+). In the older age groups, dementia prevalence increased exponentially with age, while CIND prevalence was more stable. There was not a substantial gender difference in CIND prevalence in all ages. Only in the subpopulation of higher educated subjects, women had a higher prevalence of both dementia and CIND than men. Lower educated subjects had a higher prevalence of both dementia and CIND. When compared to higher educated persons, subjects without any schooling had odds ratios of 10.9 (CI 7.0-16.7) and 16.7 (CI 11.2-25.0) for dementia and CIND, respectively. CONCLUSIONS: Cognitive impairment is very common in the younger old ages (under 70 years of age), whereas dementia becomes predominant after 75 years of age. Both conditions are strongly related to the educational level.     

The relative frequency of "dementia of unknown etiology" increases with age and is nearly 50% in nonagenarians

CONTEXT: With the recent change in pathological criteria for Alzheimer disease (AD), a group of patients has emerged who do not meet pathological criteria for any well-characterized degenerative dementias. Whether these unclassified patients have vascular dementia or some other form of dementia is not known. OBJECTIVE: To determine the clinical characteristics, pathological substrate, and relative frequency of dementia not caused by well-characterized degenerative dementias. DESIGN/SETTING: Clinicopathological study of a prospectively observed sample of elderly nondemented and demented subjects recruited from our urban community. METHODS: In our series of 128 subjects with prospective neuropsychological evaluations as well as neuropathology, we identified 35 clinically nondemented subjects and 20 demented patients who did not meet pathological criteria for well-characterized degenerative dementias such as AD or dementia with Lewy bodies. The 20 demented patients were grouped together under the term dementia of unknown etiology (DUE). We compared clinical, genetic, neuropsychological, pathological, and neurochemical characteristics of the nondemented group, patients with DUE, and 28 patients with AD and no other pathological abnormality. RESULTS: Mean age at death for patients with DUE was 89.1 +/- 5.8 years compared with 79.9 +/- 11.4 years for AD (P<.001). Patients with AD and DUE did not differ in sex, risk factors, apolipoprotein E genotype, neuropsychological features, or neurological features. Hippocampal sclerosis (in 11 patients with dementia and no controls) and leukoencephalopathy (in 7 patients with dementia and 1 control) were associated with cognitive impairment; other vascular markers were not. Dementia of unknown etiology accounted for 5% of all cases of dementia among patients dying in their 70s, 21% for patients dying in their 80s, and 48% for patients dying in their 90s. CONCLUSIONS: A significant percentage of demented patients older than 80 years do not meet pathological criteria for AD or dementia with Lewy bodies. Hippocampal sclerosis and leukoencephalopathy are common in these patients but rare in clinically nondemented subjects.