Gustavo C. Román

Vascular Factors and Risk of Dementia: Design of the Three-City Study and Baseline Characteristics of the Study Population

Objective: To describe the baseline characteristics of the participants in the Three-City (3C) Study, a study aiming to evaluate the risk of dementia and cognitive impairment attributable to vascular factors. Methods: Between 1999 and 2001, 9,693 persons aged 65 years and over, noninstitutionalized, were recruited from the electoral rolls of three French cities, i.e. Bordeaux, Dijon and Montpellier. Health-related data were collected during face-to-face interviews using standardized questionnaires. The baseline examination included cognitive testing and diagnosis of dementia, and assessment of vascular risk factors, including blood pressure measurements, ultrasound examination of the carotid arteries, and measurement of biological parameters (glycemia, total, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinemia); 3,442 magnetic resonance imaging (MRI) examinations were performed in subjects aged 65–79. Measurements of ultrasound, blood, and MRI parameters were centralized. Two follow-up examinations (at 2 and 4 years) were planned. Results: After exclusion of the participants who had subsequently refused the medical interview, the 3C Study sample consisted of 3,649 men (39.3%) and 5,645 women, mean age 74.4 years, with a relatively high level of education and income. Forty-two percent of the participants reported to be followed up for hypertension, about one third for hypercholesterolemia, and 8% for diabetes; 65% had elevated blood pressure measures (systolic blood pressure ≧140 or diastolic blood pressure ≧90). The proportion of Mini-Mental State Examination scores below 24 was 7% and dementia was diagnosed in 2.2% of the participants. Conclusion: Distribution of baseline characteristics of the 3C Study participants suggests that this study will provide a unique opportunity to estimate the risk of dementia attributable to vascular factors.

Socio-Demographic Variation of Dementia Subtypes in China: Methodology and Results of a Prevalence Study in Beijing, Chengdu, Shanghai, and Xian

Objective: To characterize sociodemographic variations in the prevalence of AD and VaD in China. Methods: Data were collected in a 1997–1998, cross-sectional, door-to-door prevalence survey of 34,807 community residents ages ≧55 years in Beijing, Shanghai, Chengdu and Xian. Initial diagnoses of AD and VaD were assessed by clinicians using standardized protocols, according to the NINCDS-ADRDA and NINDS-AIREN criteria; diagnoses were confirmed after 6 months by repeating neuropsychological evaluations. Prevalence odds ratios were estimated in logistic models adjusting for survey design, age, and other sociodemographic factors. Results: We identified 732 prevalent cases of AD and 295 cases of VaD. Adjusting for all sociodemographic factors concurrently, prevalence odds of AD and VaD were higher in northern versus southern China. Age trends for AD appeared different in western and eastern China. AD also showed an age-adjusted elevation among women and, in the fully adjusted model, a gender education interaction indicating a female preponderance in the highest education group. North-south variation for VaD was age-dependent. In the fully adjusted model, for AD, widowed had significantly higher prevalence odds; for VaD, widowed persons and minorities had significantly lower prevalence odds; professionals had statistically significant and borderline lower prevalence odds for both VaD and AD; sales-service occupations had significantly lower odds for AD only. Conclusion: We observed variations in prevalence for AD and VaD in different regions and demographic groups in China that persisted after controlling for potential confounding factors. Sociodemographic factors are probable surrogates for conditions such as lifestyle, environment, comorbidities, and life expectancy.

Incidence of dementia in a rural community in Spain: The Girona cohort study

Background: Information on dementia incidence in Spanish populations is still scarce, and there is a dearth of prospective studies. Objective: To estimate the incidence rates of dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) in a population cohort aged 75 and over in a rural area in Spain. Methods: A prospective population cohort study over a 5-year period in 8 rural villages in the province of Girona. The baseline study in 1990 identified 200 prevalent cases of dementia. The dementia-free cohort included 1,260 persons aged 75 and over. This was the sample used for the incidence study. We rescreened and selectively reexamined this group in 1995 using a two-phase procedure consisting of a screening interview at home using the MMSE. Diagnoses of dementia, AD and VaD were established using the Cambridge Examination for Mental Disorders of the Elderly for surviving participants. For deceased participants, we used the Retrospective Collateral Dementia Interview to establish a diagnosis of dementia and AD according to DSM-III-R diagnostic criteria. Results: Information was obtained for 91% of the subjects at risk; 122 incident cases of dementia were identified. Incidence rates per 1,000 person-years at risk were 23.2 (95% CI = 19.1–27.3) for dementia, 10.8 (95% CI = 7.8–13.7) for AD and 9.5 (95% CI = 6.7–12.1) for VaD. All dementia subtypes showed an age-dependent pattern. Females had a relative risk of 1.8 (95% CI = 1.0–3.4) to develop AD. The inclusion of deceased cases with manifestations of dementia increased the rate of dementia incidence in 7.1 cases/1,000 person-years at risk. Conclusion: Incidence rates were similar to those reported by other cohort studies. All dementia subtypes increased with age, but incidence rates did not increase exponentially in the oldest old. Females were at increased risk for AD. The inclusion of information about dementia symptoms from relatives of deceased participants was useful in order to avoid underestimation of the dementia incidence rates. Underestimation of the incidence rates was more important in those aged 75–84 years.

Frontal MRI findings associated with impairment on the Executive Interview (EXIT25).

Abstract We examined the association between the Executive Interview (EXIT25), a bedside measure of executive control, and regional magnetic resonance imaging (MRI) pathology among 52 consecutive geriatric patients presenting to a university dementia assessment clinic. Left frontal (p < .002), left medial (p < .03), right frontal (p < .02), and right medial (p < .02) cortical lesions significantly worsened EXIT25 scores, even after adjusting for age, global cognitive impairment (on the Mini-Mental State Examination), and the severity of cortical dementia on the Qualitative Evaluation of Dementia [QED]. The EXIT25s associations with right hemisphere lesions did not persist after adjusting for left frontal lesions. Left posterior lesions did not significantly affect the EXIT25. Similarly, left frontal circuit pathology worsened EXIT25 scores (p < .05). Pathology in left anterior subcortical structures showed a trend (p = .052). EXIT25 scores were not affected by right subcortical pathology, nor by pathology in either hippocampus. We conclude that the EXIT25 is specifically affected by frontal system MRI lesions, particularly on the left. This conclusion is consistent with earlier functional neuroimaging studies associating EXIT25 performance with left mesiofrontal perfusion.

Epidemic neuropathy in Cuba A plea to end the United States economic embargo on a humanitarian basis

During 1992–1993, an epidemic of neurologic disease in Cuba affected 50,862 patients with optic neuropathy, sensorineural deafness, predominantly sensory peripheral neuropathy, and dorsolateral myelopathy. The clinical syndromes were identical to those of prisoners of war subjected to nutritional restriction in tropical prison camps during World War II (Strachans disease). A dietary deficiency of group B vitamins and sulfur-containing amino acids appears to have been the primary cause of the epidemic. This was a consequence of economic and political events in Cuba linked to the collapse of the Soviet Union and socialist countries. The recently toughened 30-year-old US economic embargo on Cuba contributed to these problems and hampered the investigation, treatment, and prevention of the epidemic. A plea is made to the neurologic community to request the lifting of the trade blockade on a humanitarian basis.

Mortality after a Diagnosis of Dementia in a Population Aged 75 and Over in Spain

Objectives: To examine the impact of incident dementia on the risk of death, taking into account other chronic illnesses potentially related to death. Design: Six-year, prospective, two-phase, observational cohort study. Setting: 8 municipalities from a rural area in Girona (Spain). Participants: A representative community-based cohort of 1,153 adults aged over 70 living at home at study enrolment. Measurements: Surviving participants underwent detailed clinical evaluation and were assessed by means of the Cambridge Examination for Mental Disorders of the Elderly. Relatives of deceased participants were interviewed using the Retrospective Collateral Dementia Interview. Mortality rates and relative risk of death for subjects with a diagnosis of dementia were calculated. The Cox proportional hazards regression model was used to assess the relationship between mortality and the diagnosis of dementia. Results: In this cohort, 40.0% (n = 49) of the subjects with a diagnosis of dementia died. The mortality rate specific to dementia was 1.0 per 100 person-years. Mortality risk ratios for dementia were 1.79 in men [95% confidence interval (CI) = 1.06–3.02], and 3.14 in women (95% CI = 2.04–4.85). The population death risk attributable to the diagnosis of dementia in our cohort was 11.8%. The most important mortality risks were severe dementia (hazard ratio = 5.7, 95% CI = 3.7–8.6), cancer (hazard ratio = 3.2, 95% CI = 2.2–4.5), heart disease, and an age over 85 (hazard ratio = 1.4, 95% CI = 1.1–1.9). Conclusion: Dementia is a major risk factor for death in advanced age, with the highest mortality rates in women. Moderate and severe dementia was associated with an increased mortality risk even after appropriate control of comorbid conditions.

Multiple sclerosis or HTLV‐I myelitis?

Several authors have demonstrated the presence of antibodies against the HTLV-I retrovirus in patients with MS. Considerable controversy exists regarding the etiologic significance, if any, of this finding, but the presence of these antibodies in the blood or CSF of MS patients has led to reconsideration of that diagnosis in certain cases. It is recommended that, before the diagnosis of MS is changed to that of HTLV-I-associated chronic myelitis, at least 2 of the following abnormalities be present: (1) clinical or electrophysiologic involvement of peripheral nerve or muscle; (2) the presence of oligoclonal bands in the serum; (3) the presence in blood or CSF of lymphocytes with multilobed nuclei; (4) a positive serologic test for syphilis; (5) the presence of a sicca syndrome; and (6) the presence of pulmonary lymphocytic alveolitis.

Cerebral small-vessel disease: what lies beyond the early years?

The term cerebral small-vessel disease (SVD) encompasses a range of features visible on brain imaging, including lacunar infarction (from the Latin lacunae , a tiny hole, pit, or cavity), leukoaraiosis (from the Greek leuko , white, and araiosis , rarefaction), enlarged perivascular spaces (producing an appearance of etat crible , or cribriform state, from the Latin cribriform , perforated), and brain microbleeds. The investigative approach to cerebral SVD—including lacunar stroke—has been revolutionized in the last 4 decades by the advent of CT and MRI, which have overcome many of the limitations imposed by the old pathology-centered approach,1 whereby low early case-fatality rates necessitated most pathologic material being examined long after clinical symptoms had occurred. MRI in particular has markedly improved our ability to detect cerebral SVD in vivo, enabling detection of microangiopathic …

rtPA in acute stroke patients with history of cognitive impairment Do not hesitate to treat

A solid body of evidence has accumulated over the past 20 years confirming the critical role of cerebrovascular disease in Alzheimer disease (AD) and other dementias of the aged.1–6 Most recently, data from the National Alzheimers Coordinating Center7 demonstrated the presence of vascular pathology in 79.9% of 4,629 brains from patients with neuropathologically confirmed AD. Lesions included atherosclerosis in the circle of Willis, arteriosclerotic leukoencephalopathy, arteriolosclerosis, large infarcts, lacunes, multiple microinfarcts, and hemorrhages. Notably, cerebral amyloid angiopathy was present in less than half of the brains (40.8%). Given the absence of an effective treatment to halt the progression of AD, the current emphasis is on dementia prevention by appropriate treatment of vascular risk factors for stroke.8,9 Once stroke occurs, optimal treatment of the acute ictus with prompt restoration of flow in the occluded vessels improves the cognitive outcome. In contrast, stroke complications such as aspiration pneumonia, hypoxemia, seizures, hypotension, or cardiac arrhythmias increase the risk of poststroke cognitive impairment 4-fold.10

Prof. William C. Koller, MD, PhD (1945–2005)

The editors and members of the editorial board of Neuroepidemiology are saddened by the unexpected death of Prof. William Koller on 3 October 2005 in Chapel Hill, N.C. Bill Koller was a long-time friend and an active member of the editorial board of Neuroepidemiology for many years. He was always generous with his time and expertise in the review of manuscripts on Parkinson’s disease, essential tremor, and movement disorders. As a rule, his careful reviews always offered the authors points of improvement based on his encyclopedic knowledge of these topics. He published more than 270 peerreviewed articles, 160 review papers and multiple books. In 1999 he became National Research Director for the National Parkinson Foundation; he was also Fellow of the American Academy of Neurology, the Movement Disorders Society, the Parkinson Study Group (1996–1999), President of WE MOVE (2001–2002), founding member of the Tremor Research Group, and the International Tremor Foundation. We convey our sympathy to his wife and sons. Gustavo C. Román , MD Editor-in-Chief Published online: March 10, 2006