Education-corrected CERAD identifies MCI and dementia in Parkinson's disease.

OBJECTIVES: This study examined whether controlling for educational background in the CERAD cognitive screening battery would affect the likelihood of patients with Parkinson's disease to fulfill criteria for mild cognitive impairment (PD-MCI) and dementia (PDD). MATERIALS & METHODS: One-hundred seventeen patients with PD were studied. Cognitive impairment was determined as two subtest scores falling below either the standard cutoff scores or education-corrected cutoff scores. The presence of dementia was determined by clinical interview or Clinical Dementia Rating. Patients were then classified as PD-MCI and PDD according to cognitive test performance and presence/absence of dementia. RESULTS: The number of cognitively impaired patients (PD-MCI or PDD) was significantly higher when education-controlled cutoff scores were used (62.5% vs 38%). Correspondingly, the number of false negatives (demented PD patients performing normally in CERAD) was significantly lower when education-corrected cutoff scores were used (4% vs 10%). CONCLUSIONS: Controlling for education increases the sensitivity of the CERAD for PD-MCI and PDD.

Apathy is associated with activities of daily living ability in Parkinson's disease.

BACKGROUND: Neuropsychiatric symptoms and impairment in performing activities of daily living (ADL) in patients with Parkinson's disease (PD) are strong predictors of the overall caregiver burden and they increase the risk for nursing home admission of the patients. The purpose of the present study was to assess the association of neuropsychiatric symptoms and ADL functions in PD. METHODS: A total of 73 community-dwelling PD patients were studied. The mean age of the patient group was 65 years and the mean disease duration was 9 years. The Neuropsychiatric Inventory was used to measure neuropsychiatric symptoms, and ADL abilities were measured by the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. RESULTS: The prevalence of neuropsychiatric symptoms in patients with PD was 73%. The most common symptoms were depression, anxiety, irritability, apathy and agitation. ADL ability correlated significantly with apathy (p < 0.002) even when adjusted for motor symptoms. CONCLUSION: Apathy was significantly associated with ADL in PD. The result indicates that more attention should be paid to identifying apathy and targeting therapeutic interventions.

CERAD test performance and cognitive impairment in Parkinson's disease.

OBJECTIVES: Many patients with Parkinson's disease (PD) develop mild cognitive impairment (PD-MCI) and dementia (PDD). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neurocognitive test battery was originally developed to identify early Alzheimer's disease, but it has become a widely used screening instrument also for other types of dementia. The aim of the study was to examine differences in CERAD test performances between cognitively intact and impaired PD patients. MATERIALS AND METHODS: Eighty-eight PD patients participating in a rehabilitation course were studied. The Clinical Dementia Rating (CDR) was used to assess cognitive impairment. Sixty-six patients were cognitively intact and 22 had cognitive impairment (≥1 in two or more domains or a sum of boxes score of ≥3). The Finnish CERAD test battery was used to measure cognitive functions in seven different domains (language functions, verbal learning, visuospatial functions, delayed recall, memory consolidation, recognition memory, and executive functions). RESULTS: There were significant differences between the cognitively intact and impaired patients in six CERAD subtests (wordlist learning sum, wordlist delayed recall, constructional praxis recall, clock drawing, verbal fluency and constructional praxis copy) when controlling for covariates (disease duration, motor symptoms, age, and education). No differences were observed in memory consolidation scores. CONCLUSIONS: The results indicate that mild cognitive impairment in PD is related to deficits in memory, executive functions, and visuospatial functions. The memory deficit is non-amnestic and does not entail accelerated forgetting. CERAD shows promise in identifying PD patients with cognitive impairment and increased risk of dementia.

A comparison of the cumulative incidence and early risk factors for psychotic disorder in young adults in the Northern Finland Birth Cohorts 1966 and 1986.

AIMS: Few studies have compared time trends for the incidence of psychosis. To date, the results have been inconsistent, showing a decline, an increase or no significant change. As far as we know, no studies explored changes in prevalence of early risk factors. The aim of this study was to investigate differences in early risk factors and cumulative incidences of psychosis by type of psychosis in two comparable birth cohorts. METHODS: The Northern Finland Birth cohorts (NFBCs) 1966 (N = 12 058) and 1986 (N = 9432) are prospective general population-based cohorts with the children followed since mother's mid-pregnancy. The data for psychoses, i.e. schizophrenia (narrow, spectrum), bipolar disorder with psychotic features, major depressive episode with psychotic features, brief psychosis and other psychoses (ICD 8-10) were collected from nationwide registers including both inpatients and outpatients. The data on early risk factors including sex and place of birth of the offspring, parental age and psychosis, maternal education at birth were prospectively collected from the population registers. The follow-up reached until the age of 27 years. RESULTS: An increase in the cumulative incidence of all psychoses was seen (1.01% in NFBC 1966 v. 1.90% in NFBC 1986; p < 0.001), which was due to an increase in diagnosed affective and other psychoses. Earlier onset of cases and relatively more psychoses in women were observed in the NFBC 1986. Changes in prevalence of potential early risk factors were identified, but only parental psychosis was a significant predictor in both cohorts (hazard ratios ≥3.0; 95% CI 1.86-4.88). The difference in psychosis incidence was not dependent on changes in prevalence of studied early risk factors. CONCLUSIONS: Surprisingly, increase in the cumulative incidence of psychosis and also changes in the types of psychoses were found between two birth cohorts 20 years apart. The observed differences could be due to real changes in incidence or they can be attributable to changes in diagnostic practices, or to early psychosis detection and treatment.

Neurologic manifestations of infective endocarditis: a 17-year experience in a teaching hospital in Finland.

BACKGROUND: Many previous studies have endeavored to find appropriate means to reduce the occurrence of neurologic manifestations in patients with infective endocarditis (IE). We evaluated patients with IE-associated neurologic complications and compared them with patients with IE who did not have neurologic symptoms. Particular attention was focused on assessing the impact of cardiac surgery and the presence of potential risk factors for complications on the outcome of the patients. METHODS: A total of 218 episodes designated as definite or possible IE according to Duke criteria and treated during the years 1980 through 1996 in a Finnish teaching hospital were retrospectively evaluated for neurologic manifestations. RESULTS: Neurologic complications were identified in 55 episodes (25%), with an embolic event as the most frequent manifestation (23/55; 42%). In the majority (76%) of episodes, the neurologic manifestation was evident before antimicrobial treatment was started, being the first sign of IE in 47% of episodes. Only 1 recurrent cerebral embolization was observed. Neurologic complications were significantly associated with Staphylococcus aureus infection (29% vs 10%; P =.001) and with IE affecting both the aortic and the mitral valves (56% vs 23%; P<.01), but not with echocardiographic detection of vegetations or anticoagulant therapy. Death during the acute phase of IE occurred in 13 episodes (24%) with neurologic complications and in 17 episodes (10%) without neurologic complications (P<.03). In episodes with neurologic complications, the IE-associated mortality rate was 25% (10/40) in the medical treatment group and 20% (3/15) in the surgical group. No neurologic deterioration was observed in these surgically treated patients postoperatively. CONCLUSIONS: Our results reinforce the belief that rapid diagnosis and initiation of antimicrobial therapy may still be the most effective means to prevent neurologic complications. These data underscore the importance of diagnostic alertness to the prognosis of patients with IE.

Interaction between parental psychosis and early motor development and the risk of schizophrenia in a general population birth cohort.

BACKGROUND: Delayed motor development in infancy and family history of psychosis are both associated with increased risk of schizophrenia, but their interaction is largely unstudied. AIM: To investigate the association of the age of achieving motor milestones and parental psychosis and their interaction in respect to risk of schizophrenia. METHODS: We used data from the general population-based prospective Northern Finland Birth Cohort 1966 (n=10,283). Developmental information of the cohort members was gathered during regular visits to Finnish child welfare clinics. Several registers were used to determine the diagnosis of schizophrenia among the cohort members and psychosis among the parents. Altogether 152 (1.5%) individuals had schizophrenia by the age of 46 years, with 23 (15.1%) of them having a parent with psychosis. Cox regression analysis was used in analyses. RESULTS: Parental psychosis was associated (P<0.05) with later achievement of holding the head up, grabbing an object, and walking without support. In the parental psychosis group, the risk for schizophrenia was increased if holding the head up (hazard ratio [HR]: 2.46; degrees of freedom [df]=1; 95% confidence interval [95% CI]: 1.07-5.66) and touching the thumb with the index finger (HR: 1.84; df=1; 95% CI: 1.11-3.06) was later. In the group without parental psychosis, a delay in the following milestones increased the risk of schizophrenia: standing without support and walking without support. Parental psychosis had an interaction with delayed touching thumb with index finger (HR: 1.87; df=1; 95% CI: 1.08-3.25) when risk of schizophrenia was investigated. CONCLUSIONS: Parental psychosis was associated with achieving motor milestones later in infancy, particularly the milestones that appear early in a child's life. Parental psychosis and touching the thumb with the index finger had a significant interaction on risk of schizophrenia. Genetic risk for psychosis may interact with delayed development to raise future risk of schizophrenia, or delayed development may be a marker of other risk processes that interact with genetic liability to cause later schizophrenia.

Ultraviolet-B-induced apoptosis and cytokine release in xeroderma pigmentosum keratinocytes.

We have assessed the ability of xeroderma pigmentosum and normal keratinocytes grown out from skin biopsies to undergo apoptosis after irradiation with ultraviolet B. Keratinocytes have been studied from xeroderma pigmentosum complementation groups A (three biopsies), C (three biopsies), D (one biopsy), xeroderma pigmentosum variant (two biopsies), and Cockayne syndrome (one biopsy). The three xeroderma pigmentosum group A and the xeroderma pigmentosum group D samples were at least six times more sensitive than normal cells to ultraviolet B-induced apoptosis. The xeroderma pigmentosum variant samples showed intermediate susceptibility. Xeroderma pigmentosum group C samples proved heterogeneous: one showed high sensitivity to apoptosis, whereas two showed near normal susceptibility. The Cockayne syndrome sample showed the high susceptibility of xeroderma pigmentosum groups A and D only at a higher fluence. These results suggest that the relationships between repair deficiency, apoptosis, and susceptibility to skin cancer are not straightforward. Ultraviolet B-induced skin cancer is also thought to be due in part to ultraviolet B-induced impairment of immune responses. The release of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha from cultured xeroderma pigmentosum keratinocytes tended to occur at lower fluences than in normals, but was less extensive, and was more readily inhibited at higher fluences of ultraviolet B.

Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation.

BACKGROUND AND PURPOSE: CADASIL is an autosomal dominant arteriopathy, characterized by multiple brain infarcts, cognitive decline, and finally dementia, which is caused by mutations in Notch3 gene encoding a Notch3 receptor protein. We describe the clinical, neuropsychological, imaging, genetic, and skin biopsy findings in a CADASIL patient homozygous for the C475T mutation resulting in R133C amino acid substitution, in comparison to 9 age-matched heterozygous patients with the same mutation. METHODS: The patients were examined clinically and neuropsychologically and with MRI and positron emission tomography for assessment of cerebral blood flow. The gene defect was analyzed by sequencing the products of polymerase chain reaction of exons 3 and 4 of the Notch3 gene. Dermal arteries were analyzed electron microscopically. RESULTS: The homozygous patient had his first-ever stroke at age 28 years. This is markedly earlier than the average, but the patient's heterozygous son had his first transient ischemic attack-like episode at the same age and another heterozygous patient had his first-ever stroke when only 2 years older. He was neuropsychologically more severely deteriorated than all but 1 of the heterozygous patients. These 2 patients had the most severe (confluent grade D) white matter MRI changes. Positron emission tomography showed markedly reduced cerebral blood flow. Skin biopsy revealed profuse deposits of granular osmiophilic material. The progression of disease in the homozygous case was, however, slower than in the most severely affected heterozygous patient. CONCLUSIONS: Our homozygous patient's phenotype is within the clinical spectrum of CADASIL, although at its severe end. Thus, CADASIL may follow the classic definition of a dominant disease, according to which the heterozygous and homozygous patients are clinically indistinguishable.

Diagnosis and epidemiology of Parkinson's disease.

The diagnosis of Parkinson's disease is purely a clinical diagnosis. The most common types of diagnostic error are a failure either to recognize the early, or unusual symptoms, or to differentiate other tremors and extrapyramidal syndromes from Parkinson's disease. The prevalence of Parkinson's disease is increasing. This has resulted from the reduction of the excess mortality by levodopa treatment. In the near future, there will be more older parkinsonian patients with a more prolonged duration of the disease.

Epidemiological approaches to the etiology of Parkinson's disease.

In the search for the cause of Parkinson's disease epidemiology serves several purposes. Valuable clues to the etiology may be derived from the epidemiological features of the disease, and the subsequent search for risk factors in analytical studies can be narrowed correspondingly. On the other hand, knowledge of the epidemiology of Parkinson's disease is necessary in creating etiological hypotheses, since only hypotheses consistent with the epidemiological profile deserve careful testing.

Progression and survival in Parkinson's disease.

Parkinson's disease is a progressive disorder and no permanent cure has ever been documented. The clinical onset, which usually occurs at an age of 55-65 years, is probably preceded by a preclinical period of two or more decades. The progression rate of the disease is extremely variable in different patients; in individual patients on the other hand, the progression of motor symptoms is fairly constant. The tremor-dominant type of the disease usually has a more favourable prognosis than the hypokinetic type. Onset at an older age may be associated with a faster progression rate and the development of cognitive failure. In natural conditions, the average duration of Parkinson's disease is 10 years, although with a considerable range. The disease shortens life expectancy, which can be restored at least partially by treating patients with levodopa and other modern drugs. The highest benefit in increasing life expectancy is obtained when the treatment is initiated at a relatively early stage of the disease.

Brain dopamine turnover and the relief of parkinsonism.

The relationship between dopamine receptor activation and the relief of parkinsonian clinical features was studied in 40 patients with Parkinson's disease. Treatment with dopamine receptor agonists, piribedil or bromocriptine, decreased significantly both the basal level and probenecid-induced accumulations of homovanillic acid (HVA) in the CSF. But there were no changes in the concentrations of 5-hydroxyindole acetic acid (5-HIAA). Correlation analyses showed that patients who improved with both the dopamine agonists used had significantly lower probenecid response of HVA in the CSF and a less severe disease condition than those without beneficial effect. This relationship between dopamine receptor activation and improvement of parkinsonian disability suggests that the therapeutic efficacy of dopamine receptor agonists depends on the functional capacity of brain dopaminergic mechanisms.

Influenza virus antibodies in Parkinsonism. Comparison of postencephalic and idiopathic Parkinson patients and matched controls.

Hemagglutination inhibiting antibodies to four influenza virus strains: A/Swine/1976/30 (HswN1), A/PR/8/34 (HON1), A/England/1/51 (H1N), and A/Singapore/1/57 (H2N2), were studied in blood serum specimens from 20 patients with postencephalitic and 55 patients with idiopathic Parkinson disease and their age- and sex-matched controls. No significant differences were observed in the distribution or the mean titers of antibodies to any of the four strains tested, when the postencephalitic patients and their controls were compared. The postencephalitic group was also similar to the idiopathic group with regard to the influenza antibodies.

Herpes simplex virus subunit antibodies in patients with Parkinson's disease.

Serum IgG antibodies against herpes simplex virus (HSV) type 1 capsid, envelope, and excreted antigens in 52 patients with idiopathic Parkinson's disease, and in their age- and sex-matched controls, were assayed with a solid-phase radioimmunoassay. When compared with the controls, patients with Parkinson's disease were found to have a substantially increased antibody response against each of the HSV subunit antigens tested. The increased antibody response in patients with Parkinson's disease was not associated with the occurrence of recurrent HSV infections, since the difference in antibody levels was most evident when comparing patients without recurrent HSV infections with their respective control group. Consequently, the increased HSV antibody response in patient with Parkinson's disease might depend on some antigenic stimulation other than ordinary recurrent HSV infections, or alternatively, on the generally enhanced immunological reaction of the patients against HSV.

Herpesviruses and parkinsonism. Herpes simplex virus types 1 and 2, and cytomegalovirus antibodies in serum and CSF.

Antibodies against herpes simplex virus (HSV) types 1 and 2 and cytomegalovirus (CMV) were assayed with a microindirect hemagglutination (IHA) test in the serum of 67 pairs of patients with Parkinson's disease and controls. Cerebrospinal fluid from 30 pairs was assayed. All patient and control serum was tested with a radioimmunoassay (RIA) for antibodies against HSV type 1 subunit antigens. Serum IHA antibody level against HSV type 1 was increased in patients with Parkinson's disease and RIA antibody levels against the same viral antigen were significantly higher in the patients than controls. Herpes simplex virus type 2 and CMV serum antibodies were equal in the patient and control groups. Most of the CSF samples tested negatively for IHA; small and comparable numbers of the patients and controls had low antibody levels against HSV and CMV antigens.

Extrapyramidal signs in Alzheimer's disease.

The occurrence and type of extrapyramidal signs were investigated in 143 patients with dementia of the Alzheimer type. Only 8% of the patients were free of extrapyramidal signs. The most common type of extrapyramidal involvement was a rigid, hypokinetic, and hypomimic pattern. Resting tremor was rarely encountered. Dyskinetic signs, mostly orofacial, were seen in 17%. These observations suggest that in most patients with advanced Alzheimer's disease, there is a striatal dopaminergic hypofunction, appearing clinically as hypokinesia and rigidity. However, some patients exhibit predominantly dyskinetic signs, implying more complex basal ganglia dysfunction.

Parkinson's disease in a nationwide twin cohort.

The Finnish Twin Cohort includes all Finnish same-sexed twins born before 1958 and alive in 1967; the number of individuals alive in 1975 was 33,247. We performed a search for cases with Parkinson's disease among this cohort by linking the Twin Cohort Register with the Finnish Hospital Discharge Register and the Finnish Sickness Insurance Register. We ascertained altogether 42 cases of Parkinson's disease occurring in 41 twin including 18 monozygotic pairs, 14 dizygotic pairs, and nine pairs of undetermined zygosity. Only one dizygotic pair was concordant for Parkinson's disease; all other pairs were discordant. In 1981, the expected number of cases among the Twin Cohort, calculated according to the age- and sex-specific prevalence rates of Parkinson's disease in Finland, was 33. At the same time, the observed number of patients alive was 35. This study, further substantiating the low concordance for Parkinson's disease in monozygotic as well as in dizygotic twins and indicating that the prevalence of Parkinson's disease in twins compares with the prevalence in the general population, suggests that Parkinson's disease is an acquired disease not caused by a hereditary process.

Changing epidemiology of Parkinson's disease in southwestern Finland.

OBJECTIVE: Investigation of the epidemiology of PD in southwestern Finland in 1992 (population 196,864), including urban and rural areas, with a comparison with a similar study, done in the same area in 1971, to evaluate the temporal pattern. METHODS: Community-based method of patient ascertainment with personal investigation of cases. RESULTS: The age-adjusted prevalence (to the Finnish general population in 1991) was 139 per 100,000 population in 1971 and 166 in 1992. Prevalence ratio for PD in men versus women was 1.2 (NS) in 1971 and 1.7 in 1992 (p < 0.001); in the rural versus urban populations the prevalence ratio was 0.8 (NS) in 1971 and 1.3 in 1992 (p = 0.013). The age-specific prevalence rates showed a male preponderance in all age groups in 1992 and a rural preponderance in the age groups over 60 years. In 1992, compared with 1971, the male and rural preponderance occurred in the age groups over 70 years. The age-adjusted incidence was 15.7 per 100,000 population in 1971 and 14.9 in 1992. Relative risk for PD in men versus women was 0.9 (NS) in 1971 and 1.9 (p < 0.001) in 1992, and in rural versus urban populations 1.4 (p = 0.093) in 1992. CONCLUSIONS: A very significant male and a significant rural predominance, not seen in 1971, suggests a possible environmental causative factor, perhaps more frequent in the rural environment, associated with PD. Men may be either more exposed to it or more susceptible to its effects than women.

Human surfactant protein--A gene locus for genetic studies in the Finnish population.

Lung surfactant lowers the surface tension but surfactant proteins also have other functions. Surfactant protein A (SP-A) has a well-defined role in innate immunity. The gene locus for human SP-A genes is in chromosome 10q21 through q24 and consists of two highly homologous functional SP-A genes (SP-A1 and SP-A2) and a pseudogene. Several alleles that differ by a single amino acid have been identified for both SP-A genes. The SP-A gene locus has been shown to be sufficiently polymorphic for genetic studies in the American population. In this study, we analysed the SP-A allele frequencies in a Finnish population (n = 790) and found them to differ from the frequencies observed in US. Furthermore, we describe several new alleles for both SP-A genes. The heterozygosity indices and polymorphism information content values ranged between 0.50--0.62 indicating that SP-A gene locus is polymorphic enough for studies associating the locus with pulmonary diseases.