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Case-control studies of Alzheimer's disease were re-analysed to examine the association of Alzheimer's disease with family history in first degree relatives of dementia, Down's syndrome and Parkinson's disease. Overall, the relative risk of Alzheimer's disease for those with at least one first degree relative with dementia was 3.5 (95% confidence interval 2.6-4.6). Stratification according to age of onset of Alzheimer's disease showed that the relative risk decreased with increasing onset age. However, among patients with an onset of disease after 80 years, there were still significantly more subjects with one or more first degree relatives with dementia as compared to controls (relative risk 2.6; 95% confidence interval 1.3-5.2). The relative risk of Alzheimer's disease was significantly lower in patients who had one first degree relative with dementia (relative risk 2.6; 95% confidence interval 2.0-3.5) as compared to those who had two or more affected relatives (relative risk 7.5; 95% confidence interval 3.3-16.7). Furthermore, the re-analysis showed a significant association between Alzheimer's disease and family history of Down's syndrome (relative risk 2.7; 95% confidence interval 1.2-5.7), which was strongest in those patients who had a positive family history of dementia. The relative risk of Alzheimer's disease for those with a positive family history of Parkinson's disease was 2.4 (95% confidence interval 1.0-5.8).

Little is known about the population-based prevalence of neuropsychiatric symptoms in mild cognitive impairment (MCI).To estimate the prevalence of neuropsychiatric symptoms in MCI and normal cognitive aging in a defined population.Cross-sectional study derived from an ongoing population-based prospective cohort study.The Mayo Clinic Study of Aging.We studied a random sample of 1969 individuals without dementia from the target population of 9965 elderly persons residing in Olmsted County (Minnesota) on the prevalence date (October 1, 2004). Neuropsychiatric data were available for 319 of 329 subjects with MCI (97.0%) and 1590 of 1640 subjects with normal cognition (97.0%). Neurologic, cognitive, and neuropsychiatric data were obtained from the study participants. A classification of MCI, dementia, and normal cognitive aging was adjudicated by an expert consensus panel. Accordingly, 329 subjects were classified as having MCI and the remaining 1640 subjects were classified as having normal cognition.Neuropsychiatric Inventory Questionnaire score.Multivariate logistic regression analyses were conducted after adjusting for age, sex, and educational status. By considering both the odds ratio (OR) and the frequency of a symptom, the most distinguishing features between the 2 groups were apathy (OR, 4.53; 95% confidence interval [CI], 3.11-6.60; P.001), agitation (3.60; 2.18-5.92; P.001), anxiety (3.00; 2.01-4.48; P.001), irritability 2.99; 2.11-4.22; P.001), and depression (2.78; 2.06-3.76; P.001). The OR was highest for delusion (8.12; 95% CI, 2.92-22.60; P.001); however, it was rare in both subjects with MCI (11 of 319 [3.4%]) and those with normal cognition (6 of 1590 [0.4%]). Thus, the population attributable risk for delusion was only 2.62% compared with 14.60% for apathy.Nonpsychotic symptoms affected approximately 50% of subjects with MCI and 25% of subjects with normal cognition. In contrast, psychotic symptoms were rare.

Context Relatives of patients with Parkinson disease (PD) have an increased risk of PD and other neurologic disorders; however, their risk of psychiatric disorders remains uncertain. Objective To study the risk of depressive disorders and anxiety disorders among first-degree relatives of patients with PD compared with first-degree relatives of controls. Design, Setting, and Participants In a population-based, historical cohort study, we included 1000 first-degree relatives of 162 patients with PD and 850 first-degree relatives of 147 controls. Both patients with PD and controls were representative of the population of Olmsted County, Minnesota. Main Outcome Measures Documentation of psychiatric disorders was obtained for each relative separately through a combination of telephone interviews with the relatives (or their proxies) and review of their medical records from a records-linkage system (family study method). Psychiatric disorders were defined using clinical criteria from the DSM-IV or routine diagnoses. Results We found an increased risk of several psychiatric disorders in first-degree relatives of patients with PD compared with first-degree relatives of controls (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.21-1.95; P P = .006) and anxiety disorders (HR, 1.55; 95% CI, 1.05-2.28; P = .03). The results were consistent in analyses that adjusted for type of interview, excluded relatives who developed parkinsonism, or excluded relatives who developed both a depressive disorder and an anxiety disorder. Conclusion These findings suggest that depressive disorders and anxiety disorders may share familial susceptibility factors with PD.

Background The evidence for increased risk of dementia in relatives of patients with Parkinson disease (PD) remains conflicting. Objective To study the risk of cognitive impairment or dementia in first-degree relatives of patients with PD. Design, Setting, and Participants We conducted a historical cohort study of 1019 first-degree relatives of 162 patients with PD and of 858 relatives of 147 matched controls representative of the population of Olmsted County, Minnesota. In addition, we studied 2716 first-degree relatives of 411 patients with PD referred to Mayo Clinic. Main Outcome Measures We administered via telephone a cognitive test directly to relatives or a dementia questionnaire to proxies. For relatives reported by proxies to have dementia, we obtained copies of their medical records to confirm the diagnosis. We also obtained dementia information from a medical records-linkage system. Results In the overall population-based sample, the risk of cognitive impairment or dementia was increased in relatives of patients with PD compared with relatives of controls (hazard ratio, 1.37; 95% confidence interval, 1.03-1.81; P = .03) and was particularly increased in relatives of patients with onset of PD at age 66 years or younger (youngest tertile; hazard ratio, 1.73; 95% confidence interval, 1.21-2.46; P = .003). The findings were consistent in several sensitivity analyses. In the referral-based sample, the risk of cognitive impairment or dementia in relatives increased with younger age at onset of PD but did not vary by other clinical characteristics. Conclusion Cognitive impairment or dementia may share familial susceptibility factors with PD (genetic or nongenetic).

Context Epidemiologic studies have reported that cigarette smoking is inversely associated with Parkinson disease (PD). However, questions remain regarding the effect of age at smoking onset, time since quitting, and race/ethnicity that have not been addressed due to sample size constraints. This comprehensive assessment of the apparent reduced risk of PD associated with smoking may provide important leads for treatment and prevention. Objective To determine whether race/ethnicity, sex, education, age at diagnosis, and type of tobacco modify the observed effects of smoking on PD. Design, Setting, and Participants We conducted the first ever pooled analysis of PD combining individual-level data from 8 US case-control and 3 cohort studies (Nurses' Health Study, Health Professionals Follow-Up Study, and Honolulu-Asia Aging Study) conducted between 1960 and 2004. Case-control studies provided data for 2328 PD cases and 4113 controls matched by age, sex, and ethnicity; cohort studies contributed 488 cases and 4880 controls selected from age- and sex-matched risk sets. Main Outcome Measure Incident PD. Results We confirmed inverse associations between PD and smoking and found these to be generally stronger in current compared with former smokers; the associations were stronger in cohort than in case-control studies. We observed inverse trends with pack-years smoked at every age at onset except the very elderly (>75 years of age), and the reduction of risk lessened with years since quitting smoking. The risk reductions we observed for white and Asian patients were not seen in Hispanic and African American patients. We also found an inverse association both for smoking cigars and/or pipes and for chewing tobacco in male subjects. Conclusions Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study.

Context: Relatives of patients with Parkinson disease (PD) have an increased risk of PD and other neurologic disorders;however,theirriskofpsychiatricdisordersremains uncertain. Objective:Tostudytheriskofdepressivedisordersand anxiety disorders among first-degree relatives of patients with PD compared with first-degree relatives of controls. Design, Setting, and Participants: In a populationbased, historical cohort study, we included 1000 firstdegree relatives of 162 patients with PD and 850 firstdegree relatives of 147 controls. Both patients with PD andcontrolswererepresentativeofthepopulationofOlmsted County, Minnesota. Main Outcome Measures: Documentation of psy

Objective To estimate the prevalence of neuropsychiatric symptoms among subjects with mild cognitive impairment (MCI) in a defined population. Background The population-based prevalence of neuropsychiatric symptoms in MCI is unknown except for a recent report (Lyketsos et al, 2002, JAMA) that has not yet been replicated. Design/Methods The Mayo Clinic Study of Aging is an NIH-funded population-based study that was launched in October 2004. It is designed to estimate the prevalence and incidence of MCI. Elderly individuals of age 70 to 89 years are being recruited by using a stratified random sampling from the target population of Olmsted County, Minnesota (equal allocation of men and women). All participants undergo neurological, neuropsychiatric, and psychometric evaluations. A consensus panel of behavioral neurologists, geriatrician, neuropsychiatrist, neuropsychologists, and nurses determined the classification of normal cognitive aging, MCI, or dementia based on standard definitions. The Neuropsychiatric Inventory (NPI) was administered to all participants, and the prevalence of symptoms in MCI cases was compared to cognitively normal individuals (controls), matched by age and gender (1 case to 3 controls), by using chi-square or Fisher9s exact test. Results Neuropsychiatric data were available on 104 participants with MCI and 312 cognitively normal individuals. The prevalence of apathy was 24% in MCI ( n = 25/104) vs 6.1% (19/312) in cognitively normal individuals ( p

Background It remains unknown whether depression and apolipoprotein E genotype are risk factors for incident mild cognitive impairment (MCI). Objective To determine whether elderly individuals with depression (measured by the short Geriatric Depression Scale) are at increased risk of developing incident MCI. Design Prospective cohort study. Setting Primary care clinic. Participants A cohort of 840 cognitively normal elderly subjects without depression at recruitment who were followed up prospectively for a median of 3.5 years (range, 0.4-12.8 years). Subjects who developed depression (score of ≥6 on the short Geriatric Depression Scale; depression cohort) were compared with all remaining subjects (referent cohort). Main Outcome Measures Incidence of MCI (primary outcome) and incidence of MCI or dementia (composite secondary outcome). Results Individuals in the depression cohort were at significantly increased risk of subsequent incident MCI (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1) after adjusting for age (time scale), sex, and education, and considering dementia as a competing outcome. The association was stronger in men but did not vary by severity of depression. We observed a synergistic interaction between apolipoprotein E genotype (e3/e4 or e4/e4) and depression (joint effect HR, 5.1; 95% CI, 1.9-13.6; test for additive interaction, P = .03). We found a similar association between depression and the subsequent composite outcome of incident MCI or dementia (HR, 2.6; 95% CI, 1.6-4.3). Conclusions Cognitively normal elderly individuals who develop depression are at increased risk of subsequent MCI. We found a synergistic interaction between depression and apolipoprotein E genotype.

Background Information on the incidence of nondegenerative and nonvascular dementia is limited. Design We used the records-linkage system of the Rochester Epidemiology Project to ascertain incident cases of dementia in Rochester, Minn, from January 1, 1990, through December 31, 1994. To define causes of dementia, we reviewed all diagnoses, imaging study results, laboratory test results, and clinical courses, as recorded historically in the patient dossier. Results We found 560 incident cases of dementia, and 60 of them (10.7%) had onset before the age of 70 years (younger-onset group). Forty-three cases (7.7%) were due to nondegenerative nonvascular causes and represented 30.0% of the total in the younger-onset group, but only 5.0% of the total in the older-onset group (aged 70-99 years). The most common nondegenerative nonvascular causes were cancer with or without brain metastases (n = 13), chronic alcoholism (n = 7), and chronic mental illness (n = 11). There were no cases of dementia due to normal-pressure hydrocephalus, subdural hematoma, hypothyroidism, vitamin B 12 deficiency, or neurosyphilis. There were 2 individuals with acute confusion due to subdural hematoma and 1 with hypothyroidism whose cognition normalized with therapy. Conclusions Nondegenerative nonvascular causes were more common than expected in patients with a younger onset of dementia. None of the patients with dementia reverted to normal with treatment of the putative reversible cause.

Background The validity of the clinical diagnosis of vascular dementia (VaD) remains suboptimal. Objective To investigate clinicopathologic correlations in VaD. Methods We used the medical records-linkage system of the Rochester Epidemiology Project to identify incident cases of dementia in Rochester, Minn, from January 1, 1985, through December 31, 1989. Dementia and Alzheimer disease (AD) were defined by the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Vascular dementia was defined by criteria including imaging results. Pathological characteristics of AD were quantified by means of standard scoring methods for neurofibrillary tangles and neuritic plaques. Vascular pathological findings were assessed by expert neuropathological opinion. Results Of 419 patients with dementia who died before the study, neuropathological examination results were available in 89 (21%) with median age at onset of 80 years (range, 50-96 years; 52 [58%] women). Pathological diagnoses were AD in 45 patients (51%), pure VaD in 12 (13%), combined AD and VaD in 11 (12%), and other diagnoses in the remaining 21 patients. Criteria for VaD that required either a temporal relationship between a stroke and dementia onset or worsening, or bilateral infarctions in specified locations demonstrated on imaging results (Mayo Clinic criteria) had 75% sensitivity and 81% specificity for pure VaD (positive likelihood ratio, 3.9; 95% confidence interval, 2.2-6.7). Five cases of pure VaD lacked the temporal relationship and accounted for the imperfect sensitivity of the criteria. Conclusions In this population-based autopsy study, the presence of vascular pathological characteristics in the absence of major AD pathological findings was common. Pure VaD without overt clinical strokes remains a challenge for antemortem diagnosis.

To compare survival in incident cases of Parkinson disease (PD) with survival in subjects free of PD from the general population.We used the medical records linkage system of the Rochester Epidemiology Project to identify incident cases of PD in Olmsted County, Minnesota, for the period 1976-1995. Cases were matched by age and sex to referent subjects from the same population. For 196 cases and 185 referent subjects, we studied survival between the date of diagnosis of PD (or index date) and death, loss to follow-up, or end of the study (May 1, 2000).The median length of follow-up was 7.2 years for cases and 8.0 years for referent subjects; 110 patients with PD and 79 referent subjects died during follow-up. The median survival was 10.3 years in cases and 13.4 years in referent subjects. The relative risk (RR) of death was 1.60 (95% confidence interval [CI], 1.20-2.14; P =.002) overall, 1.81 (95% CI, 1.15-2.84; P =.01) in women, and 1.49 (95% CI, 1.01-2.20; P =.04) in men. There was a decreasing trend in the RR of death according to age at onset of PD (in tertiles): younger than 67 years, RR, 2.04 (95% CI, 0.99-4.19; P =.05); 67 to 76 years, RR, 1.76 (95% CI, 1.08-2.86; P =.02); and older than 76 years, RR, 1.48 (95% CI, 0.95-2.29; P =.08). Patients with PD who had both rest tremor and pronounced asymmetry had a better prognosis than patients with neither clinical characteristic. Patients with PD who smoked survived better than expected.Patients with PD face a higher risk of death compared with subjects free of PD from the general population. Certain clinical characteristics and smoking modify survival.

Objective To investigate the relationship between features and definitions of vascular dementia (VaD) and survival. Design We used the medical records linkage system of the Rochester Epidemiology Project to identify incident cases of dementia in Rochester from January 1, 1985, through December 31, 1989. Dementia and Alzheimer disease were defined using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition . Vascular dementia was defined by ad hoc criteria, including imaging. Each patient with dementia was matched by age and sex to a referent subject free of dementia. Patients with dementia and referent subjects were followed from the onset of dementia (or index year) through death, censoring, or the end of the study. Results We included 479 patients with incident dementia and 479 referent subjects. Overall, patients with VaD had worse mortality than referent subjects (relative risk [RR], 2.7; 95% confidence interval [CI], 1.9-3.9). Among patients with VaD, those with dementia temporally related to a stroke had a worse relative mortality (RR, 4.5; 95% CI, 2.7-7.4) than those with only imaging evidence of bilateral infarctions in gray matter structures (RR, 2.4; 95% CI, 1.5-3.8). Relative mortality estimates varied by using 3 sets of published diagnostic criteria for VaD. Patients with VaD had a higher RR of death (RR, 2.7; 95% CI, 1.9-3.9) than patients with dementia overall (RR, 1.8; 95% CI, 1.6-2.1) or patients with Alzheimer disease (RR, 1.4; 95% CI, 1.2-1.7). Conclusions The relative mortality of patients with VaD varied depending on the set of diagnostic criteria used. A temporal relationship to a stroke was the strongest predictive feature for poor survival in patients with dementia.

Background Incidence rates of Alzheimer disease (AD) were higher in women than in men in several recent European and Asian studies. Cohort studies in the United States, on the other hand, have consistently reported no difference in incidence across sex. Objective To measure age- and sex-specific incidence rates of dementia and AD for persons aged 50 years and older residing in Rochester, Minn, during 1985 to 1989. Subjects and Methods Cases were ascertained through the medical records linkage system of the Rochester Epidemiology Project, which encompasses the records of all medical care providers (including outpatient clinics, hospitals, general practitioners, and nursing homes) in Rochester. Computer indices of clinical diagnoses, histologic diagnoses, and medical procedures were screened for indications of dementia. All medical records of potential cases were reviewed and abstracted by a trained nurse abstractor. A neurologist (E.K.) confirmed the presence of dementia and established a differential diagnosis of AD using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , and estimated the year of onset. Results A total of 482 incident cases of dementia were identified; 356 of them (73.9%) had AD. For both dementia and AD, incidence rates increased steeply with age, and there were no consistent differences between men and women. The sex pattern for AD did not change after removing cases with silent bilateral infarcts on imaging. Conclusions Contrary to observations from European and Asian populations, women were not at increased risk of incident AD in Rochester. Our findings, based on a medical records linkage system, corroborate findings from several other US studies that involved the direct contact of cohort members. The consistency of findings across study designs suggests that sex or sex-related exposures do not consistently play a major role in AD causation in American populations.

To examine the contribution of cerebrovascular disease to dementia.We used the records-linkage system of the Rochester Epidemiology Project to ascertain incident cases of dementia in Rochester, Minn, for 1985 through 1989. We defined dementia using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. To define dementia types, we reviewed neuroimaging reports, which were available for two thirds of dementia cases, in addition to medical histories and neurologic examination results. Vascular dementia (VaD) was defined by 1 of the following criteria: dementia onset or worsening within 3 months of a clinical stroke or bilateral gray matter infarctlike lesions shown by imaging that fulfilled specified location criteria (critical imaging lesions).We found 482 incident cases of dementia. Overall, 10% of patients had onset or worsening of their dementia within 3 months of a stroke. Eleven percent of the incident dementia cases had bilateral gray matter lesions on imaging that were considered critical. Eighteen percent of patients had one or the other of these features (VaD by our criteria), but only 4% of patients had both. The incidence rate of VaD increased steeply with advancing age and was similar in men and women. Our incidence rates were similar to those from a recent European meta-analysis.The presence of either a stroke temporally related to dementia onset or worsening or of critical imaging lesions was common among dementia patients, whereas the occurrence of both features together was rare.

The purpose of this study was to investigate the prevalence of dementia in an Italian population using a door-to-door 2-phase design. As part of a social and health survey, we administered the Hodkinson abbreviated mental test to all persons over age 59 residing in the Commune of Appignano on January 1, 1987 (N = 778). We then investigated all subjects scoring 7 or less on the cognitive test following a standardized diagnostic protocol. We found 48 patients affected by dementia, yielding a crude prevalence ratio (cases per 100 population over age 59) of 6.2; prevalence ratios were 2.6 for Alzheimer9s disease, 2.2 for multi-infarct dementia, 0.8 for mixed dementia, 0.4 for secondary dementia, and 0.3 for unspecified dementia. Age- and sex-specific prevalence ratios increased steeply with age and were consistently higher in women for Alzheimer9s disease and in men for dementia of all types and multi-infarct dementia. Alzheimer9s disease was slightly more frequent than multi-infarct dementia; however, the most common type of dementia varied across age groups. Most cases of Alzheimer9s disease were sporadic and had a late age of onset. Comparison with other populations suggests that dementia of all types is as frequent in Appignano as elsewhere, and that Alzheimer9s disease might be more frequent in rural than in urban populations.

We investigated the association of PD with a recently reported I93M mutation of the ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene, and with a new and common polymorphic variant S18Y of the same gene. We did not identify the I93M mutation in any of 139 unrelated PD cases or 113 controls. However, S18Y polymorphism carriers had significantly lower risk of PD (odds ratio = 0.53; p = 0.03), and the risk reduction was greater for younger onset cases.

Objective: To investigate trends in the incidence of medically recognized migraine in Olmsted County, Minnesota over approximately a decade. Methods: The authors used the records-linkage system of the Rochester Epidemiology Project to identify individuals whose records included any diagnostic rubric related to headache for the 3-year period 1979 through 1981 and the 2-year period 1989 through 1990. A nurse abstracter and a neurologist (J.W.S.) reviewed the complete history of each potential case and assigned a diagnosis using the International Headache Society classification (IHS, modified). Only patients who consulted a doctor for their headache and had their initial visit for migraine within the study years were considered as incident cases. Results: The incidence of medically recognized migraine increased in female subjects between the 1979-through-1981 period and the 1989-through-1990 period for all ages, but particularly among those who were aged 10 to 49 years. The peak incidence rate at age 20 to 29 years increased from 634.5 new cases per 100,000 person-years in 1979 through 1981 to 986.4 in the 1989-through-1990 period (absolute increase 351.9; relative increase 56%). The rise in incidence in female subjects was most sizable for migrainous disorder (IHS code 1.7); smaller increases were noted for migraine without aura and with typical aura. Only a slight absolute increase in migraine incidence rates was observed in male subjects, restricted to those 10 to 19 years of age (absolute increase 174.7; relative increase 89%). Conclusions: Although the incidence rates reported here are restricted to patients who consulted a doctor for their headache, the authors suggest that the incidence of migraine has increased over time in female subjects, especially those of reproductive age. The increase was most pronounced for migrainous disorder. Incidence rates were more stable in male subjects over time.

Article abstract Using a records-linkage system, we determined the frequency and distribution of brain autopsies in residents of Olmsted County, Minnesota, in whom parkinsonism developed during 1976 through 1990. Of the 364 incident cases identified, 235 patients were deceased at the time of record abstraction. The overall autopsy rate was low (23%). Diagnostic certainty (for PD), diagnostic type (PD versus other parkinsonism), sex, age at death, and location at death were important selection factors for autopsy.

Objective: To investigate the familial aggregation of PD in a large collaborative population-based case-control study.Background: Most previous case-control studies of the familial aggregation of PD have been hospital- or clinic-based.Methods: We included 219 prevalent cases ascertained in three European populations (centers), using a two-phase design consisting of screening and examination by a neurologist. Each case was matched by age, sex, and center to three controls drawn from the same populations (n = 657). Presence of PD among first-degree relatives (parents and siblings) was determined using the family history approach for 175 cases and 481 controls.Results: Overall, a positive family history (at least one parent or sibling affected by PD) was reported in 10.3% of patients and 3.5% of controls (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.6 to 6.6). A similar association was observed when analyses were restricted to nondemented patients and controls (OR = 3.9; 95% CI = 1.7 to 8.7) or to newly diagnosed patients (OR = 3.3; 95% CI = 0.9 to 11.9). We found a significant trend of increasing risk with increasing number of affected relatives (p = 0.003). Analyses stratified by age showed a stronger association for younger PD patients (OR = 7.6; 95% CI = 1.5 to 38.9) than for older patients (OR = 2.5; 95% CI = 1.1 to 5.7).Conclusions: In this large sample of prevalent PD patients and population-matched controls, PD significantly aggregates in families, with the strength of the association being age-dependent. Therefore, familial factors, which can be genetic, environmental, or both, play a role in PD.

Objective: To study the association between estrogen replacement therapy in postmenopausal women and AD using a case-control design. Background: Studies of the effect of estrogen therapy on the risk of AD have been limited and have yielded conflicting results. Methods: Case patients were all postmenopausal women who developed AD in the quinquennium 1980 through 1984 in Rochester, MN (n = 222). One control subject from the same population and free of dementia was matched to each case patient by age (±3 years) and length of enrollment in the records-linkage system (n = 222). Estrogen exposure was defined as any form of estrogen (oral, parenteral, topical, suppository) used for at least 6 months after the onset of menopause and before the onset of AD (or corresponding year in the matched control subject). Information on dose and duration of use was abstracted. Consistent with the matched design, analyses entailed conditional logistic regression. Results: AD patients and control subjects had identical age at menarche (median: 13.0 versus 13.0 years) and age at menopause (median: 50.0 versus 50.0 years). The frequency of estrogen use was higher among control subjects than AD patients (10% versus 5%; odds ratio = 0.42; 95% confidence interval 0.18 to 0.96; p = 0.04). There was a significant trend of decreasing odds ratios with increasing duration of use. The inverse association between estrogen therapy and AD remained significant after adjustment for education and age at menopause. Conclusion: These results from a population-based study suggest that estrogen replacement therapy is associated with a reduced risk of AD in postmenopausal women.

As part of a door-to-door neuroepidemiologic survey, we investigated the frequency and distribution of essential tremor (ET) in a Sicilian municipality. During phase 1, we administered a screening instrument for tremor to 7,653 persons residing in Terrasini (Palermo province). During phase 2, neurologists evaluated those subjects who had screened positive. The diagnoses, based on specified clinical criteria, were reviewed to increase reliability across neurologists. We found 31 subjects affected by ET (17 men, 14 women); 11 patients (35.5%) reported a familial aggregation. The prevalence of ET as of November 1, 1987, was 405.1 per 100,000 for the total population, and 1,074.9 per 100,000 for those 40 years old or older. The prevalence increased with advancing age for both sexes and was slightly but consistently higher in men. Comparison with other studies suggests striking geographic variation, which may reflect genetic differences.

In a door-to-door survey conducted in two municipalities of Sicily, we ascertained the prevalence of diabetic neuropathy. Our case-finding was restricted to subjects with somatic symptoms. During phase 1, we administered a screening instrument for peripheral neuropathy to 14,540 persons residing in Santa Teresa di Riva (Messina Province) and Terrasini (Palermo Province). During phase 2, neurologists evaluated those subjects who had screened positive. Diagnoses were based on clinical criteria only, and were reviewed by an adjudication panel. We found 39 persons (27 women, 12 men) affected by diabetic neuropathy. The crude prevalence, as of November 1, 1987, was 268.2 cases per 100,000 population. The prevalence increased with advancing age for both sexes and was consistently higher in women. The most common type was distal symmetric polyneuropathy. The median time between diagnosis of diabetes mellitus and onset of diabetic neuropathy was 8 years, and almost all identified persons with diabetic neuropathy were under treatment for diabetes mellitus.

We investigated the prevalence of Parkinson's disease and other types of parkinsonism in a Sicilian population using a door-to-door two-phase approach. This design called for the administration of a brief screening instrument to all subjects who, on November 1, 1987, were residents of Terrasini (Palermo Province), Santa Teresa di Riva (Messina Province), and Riposto (Catania Province), Sicily (N = 24,496). Study neurologists using specified diagnostic criteria extensively investigated those subjects who screened positive. We found 63 subjects affected by Parkinson's disease, 21 with secondary parkinsonism, and seven with unspecified parkinsonism. The crude prevalence per 100,000 population was 371.5 for all types of parkinsonism and 257.2 for Parkinson's disease; for both entities, prevalence increased steeply with age and showed an inconsistent sex pattern. Our prevalence figures for Parkinson's disease are higher than those previously reported in Italy or elsewhere, which may be due, in part, to more complete case-ascertainment.

In 1984-85, the authors assessed the reliability of surrogate respondents to provide interview data for the specific items of a case-control study of Alzheimer's disease conducted in Italy. For all questions of the interview, responses of 52 non-demented subjects were compared to responses of their next-of-kin. In 21-27% of the pairs the next-of-kin was unable to answer questions about general anesthesia, antacid drug use, and age of mother and father at index birth. However, the surrogate respondent was able to answer 45 of 57 tested items with agreement greater than 80%. Questions about use of hard liquor and behavior pattern yielded agreement of 71-75%, while those about number of jobs, and number of cigarettes per day yielded 62-63% agreement. For those who provided information about antacid drug use, agreement was poor. These findings are encouraging for the use of next-of-kin respondents in case-control studies of Alzheimer's disease or other neurologic conditions for which the subject cannot provide historical information.

Putative risk factors for Alzheimer's disease, other than familial aggregation, are: Down's syndrome among relatives, late maternal age, head injury, viral agents, toxic exposures, and immune factors. Current epidemiologic and genetic data are inconclusive, but indicate etiologic heterogeneity. We suggest to investigate separately: autosomal dominant, familial, and sporadic cases.

This report reviews the current status of descriptive and analytic epidemiology of clinically diagnosed Alzheimer's disease (AD). Since AD can be diagnosed with certainty only at autopsy, currently available epidemiological data are based on a presumed clinical diagnosis. Current data indicate that AD represents a major health problem, at least in the developed countries. The prevalence ratio for AD ranges between 1.9 and 5.8 cases per 100 population aged 65 and over. Moreover, its prevalence is likely to increase in the next twenty years as a consequence of current demographic trends. The prevalence ratio for AD increases steeply with age and is higher in females. Incidence rates show a similar pattern, suggesting that AD should not be subdivided in a presenile and a senile form based on age of onset alone. Annual incidence rates of 2.4 cases per 100,000 population between ages 40 and 60, and 127 cases per 100,000 population after age 60 have been reported. Several case-control studies show that the occurrence of either dementia or Down's syndrome in other family members, advanced age of the mother at subject's birth, and head injury are possible risk factors.

We studied the association between smoking and Parkinson's disease (PD) through a case-control study. Several studies have shown an inverse association between smoking and PD. This association has been interpreted as spurious by some investigators, and as real and causal by others. Several other studies did not confirm the inverse association. We included 193 prevalent cases of PD ascertained in five European prevalence surveys that followed a two-phase design of screening and clinical examination. Each case was matched by center, age (±2 years), and gender to three control subjects drawn from the same populations (N = 579). Information on smoking was obtained through direct or proxy interview. Overall, there was no association between ever smoking and PD (odds ratio = 1.1; p= 0.6). Analyses stratified by age showed that ever smoking was associated with a decreased risk of PD in the younger individuals (odds ratio = 0.4; p = 0.03) and with a significant trend of increasing risk with advancing age (p = 0.003). The risk of PD in relation to smoking is strongly modified by age; smoking may be protective in the younger cases but not in the older cases. This finding may explain the conflicting results from previous studies.

Understanding the biology of sex differences is integral to personalized medicine. Cardiovascular disease and cognitive decline are two related conditions, with distinct sex differences in morbidity and clinical manifestations, response to treatments, and mortality. Although mortality from all-cause cardiovascular diseases has declined in women over the past five years, due in part to increased educational campaigns regarding the recognition of symptoms and application of treatment guidelines, the mortality in women still exceeds that of men. The physiological basis for these differences requires further research, with particular attention to two physiological conditions which are unique to women and associated with hormonal changes: pregnancy and menopause. Both conditions have the potential to impact life-long cardiovascular risk, including cerebrovascular function and cognition in women. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of hypertensive pregnancy disorders on cardiovascular disease and cognitive function later in life, and examines the effects of post-menopausal hormone treatments on cardiovascular risk and cognition in midlife women. We suggest that hypertensive pregnancy disorders and menopause activate vascular components, i.e., vascular endothelium and blood elements, including platelets and leukocytes, to release cell-membrane derived microvesicles that are potential mediators of changes in cerebral blood flow, and may ultimately affect cognition in women as they age. Research into specific sex differences for these disease processes with attention to an individual’s sex chromosomal complement and hormonal status is important and timely.