Dementia In First-degree Relatives Research Articles

Cognitive impairment of workers in a large-scale aluminium factory in China: a cross-sectional study

ObjectivesTo investigate the prevalence of mild cognitive impairment and the relationship with plasma aluminium among aluminium workers.DesignThis was a cross-sectional case-control study in the SH Aluminium Factory, China.SettingThe university and...

Familial aggregation in atypical Parkinson’s disease: a case control study in multiple system atrophy and progressive supranuclear palsy

Familial aggregation has been consistently found in PD, but it is unclear whether there is a familial aggregation in families of patients with multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). MSA and PSP cases were recruited from a two-arm case control study. One control was matched to each case for age, gender and living area. Medical history of first-degree relatives was obtained through a face-to-face questionnaire. Age-specific cumulative incidence of Parkinsonism and dementia in first-degree relatives of cases and controls was compared for MSA and PSP separately. Seventy-one pairs for MSA and their controls and 79 pairs for PSP and their controls were included. No significant familial aggregation was found in PSP. MSA cases reported Parkinsonism more often, but not dementia in their first-degree relatives than controls. MSA patients, but not those with PSP, have Parkinsonism more often in their first-degree relatives than controls.

Risk of Cognitive Impairment or Dementia in Relatives of Patients With Parkinson Disease

The evidence for increased risk of dementia in relatives of patients with Parkinson disease (PD) remains conflicting. To study the risk of cognitive impairment or dementia in first-degree relatives of patients with PD. 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. 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. 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. Cognitive impairment or dementia may share familial susceptibility factors with PD (genetic or nongenetic).

Alzheimer's disease and head circumference

Larger brains may contain more neurons and synaptic connections, providing a greater reserve against cognitive decline in Alzheimer's disease (AD). Larger head circumference (HC) may therefore be associated with later detection and diagnosis of AD. We investigated HC in nondemented individuals and AD patients using cross-sectional and prospective analyses. The cross sectional analysis compared mean HC between 592 AD patients and 459 nondemented controls. Prospective analysis was based on the same initially normal controls who were followed longitudinally for conversion to dementia. Diagnosis of AD was made by neurologists using NINDS-ADRDA criteria. When compared to AD patients, controls had a significantly larger mean HC by 0.58 cm in men and by 0.31 cm in women, but these differences were no longer significant after adjustment for age and years of education. HC varied inversely with age and directly with years of education but did not vary with presence/absence of dementia in first-degree relatives or with apolipoprotein-E (ApoE) genotype. In the prospective analysis, the hazard ratio for time to conversion to AD was not significant for HC when adjusted for age at entry, ApoE allele status, family history of dementia, gender, and years of education. ApoE allele status, first degree relative with dementia, and baseline age conferred an increased risk for conversion to AD, consistent with other studies. We observed a smaller HC in AD patients compared to nondemented individuals, but AD per se accounted for little of this difference. HC was not a statistically significant predictor for conversion to AD in our longitudinal group.

Are Dexamethasone Suppression Test Nonsuppression and Thyroid Dysfunction Related to a Family History of Dementia in Patients with Major Depression? An Exploratory Study

Recent data suggest that the low thyroid function syndrome in depression is nonspecific. They also suggest that depression may constitute a risk factor for the development of dementia, especially in atypical patients who have high rates of hypothalamo-pituitary-adrenal axis disorders. This study aimed to search for correlations among Dexamethasone Suppression Test (DST) cortisol levels, thyroid indices, and family history of dementia in patients with depression. A sample of 30 patients, aged 21 to 60 years and suffering from major depression according to DSM-IV criteria, took part in the study. Three had a family history of dementia in first-degree relatives. We measured their serum levels of free T3, free T4, thyroid-stimulating hormone, thyroid binding inhibitory immunoglobulines, thyroglobulin antibodies, and thyroid microsomal antibodies (TMAs). We applied the 1-mg DST to all patients. The statistical analysis included 1-way multivariate analysis of covariance using t tests as the post hoc tests. Significantly higher levels of TMAs were found in patients with a family history of dementia, compared with those who did not have this family history. The results of this study suggest that a more pronounced autoimmune process may characterize depression patients with a family history of dementia.

Dementia in First-Degree Relatives of Patients with Frontotemporal Dementia

Several studies have found a clustering of dementia in relatives of patients with frontotemporal dementia (FTD). This study analysed the familial aggregation of FTD specifically as well as the occurrence of dementia in general in first-degree relatives of patients with FTD. A family history study was carried out on 478 first-degree relatives of 74 index patients suffering from FTD. Cases of organic dementia and of FTD were diagnosed according to internationally accepted diagnostic criteria. Age- and sex-specific incidences of organic dementia and of FTD were calculated as was the proportion of FTD in relation to organic dementia in general; comparisons with clinical and population studies were made. There was a tenfold increase in the incidence of FTD in the first-degree relatives of FTD patients compared with the incidence of FTD in a population study. The proportion of FTD in relation to all types of organic dementia was much higher in relatives of FTD patients compared to the corresponding proportions in clinical and population-based studies. There was a small, non-significant difference between the present family history study and the population studies as regards the incidence of organic dementia. The findings suggest that hereditary and/or shared environmental factors are strongly involved in the aetiology of FTD. There were no indications of familial clustering of organic dementia in general in relatives of FTD patients.

Risk factors in clinically diagnosed Alzheimer's disease: A retrospective hospital-based case control study in Warrington

The objective of the study was to assess risk factors for Alzheimer's disease, previously reported in cases control studies from other countries. It was conducted in a psychiatric of unit for the elderly in Warrington, a town in the northwest of England. A retrospective hospital-based, case control method was used comparing 198 cases of Alzheimer's disease (ADRDANINCDS diagnostic criteria) to selected controls (164 other dementias and 176 non-dementing group) in respect of their family, medical and personal histories.The subjects included all patients referred to and seen by the author during a two-year study period. Fifty-eight of 198 Alzheimer's cases reported family history of dementia, compared with 35 of 340 controls (OR=3.27 95% CI 1.89–5.39), p <0.01. The Odds ratio for smoking was 0.68; significant only in men (0.45, p <0.05). The odds ratio for having a history of head injury was 1.52 (0.98–2.35), also significant only in male patients (OR=2.1, p <0.05). The study confirms a family history of dementia in first-degree relatives as a risk factor for Alzheimer's disease. No cases with either Down's syndrome or having family history of it were reported in the study sample. Previously reported head injury as a risk factor appears to apply to all dementias and was not confined to Alzheimer's disease. The inverse relationship with smoking was evident, but significant only in men.

Family History of Dementia and Current Depression in Nondemented Community-Dwelling Older Adults

Since it has been postulated that mood disturbance in nondemented older adults may represent a prodromal feature of dementia for a subgroup of patients, it would be expected that patients with these symptoms would evidence a greater prevalence of family history of dementia. In a sample of 3225 community-dwelling cognitively intact elderly recruited from a free memory-screening program, we found that current depression was more common in participants with a positive versus a negative family history of dementia in first-degree relatives (17% versus 11%; Fisher's Exact Test, P < .0001). This relationship remained significant after controlling for age, education, gender, ethnicity, and Folstein Mini-Mental State Examination score (OR = 1.5; 95% CI = 1.2-1.9, Wald X2 = 15.5, P < .001). The results suggest that symptoms of depression may herald the onset of an incipient dementia syndrome in a subset of geriatric patients. Alternatively, the results may be indicative of familial aggregation of dementia and depression.

Familial aggregation in frontotemporal dementia.

Frontotemporal dementia (FTD) is a common, non-Alzheimer's dementia. Its familial occurrence has been reported, but the frequency of positive family history is unknown. We carried out a nationwide genetic-epidemiologic study of FTD in the Dutch population of 15 million people. The family history of dementia was analyzed in 74 FTD patients and 561 age- and gender-matched control subjects. We found one or more first-degree relatives with dementia before age 80 in 38% (28 of 74) of FTD patients, but only in 15% (84 of 561) of control subjects. Ten percent of FTD patients had two or more first-degree relatives with dementia compared with 0.9% of the control subjects. Seven percent of FTD patients showed the ApoE4E4 genotype versus 2.3% of the control subjects. The first-degree relatives of FTD had a risk of 22% for dementia before age 80 compared with 11% in relatives of control subjects. The age of onset of dementia in affected first-degree relatives of FTD patients (60.9+/-10.6 years) was significantly lower than among affected relatives of control subjects (72.3+/-8.5 years). The first-degree relatives of FTD patients were 3.5 times (95% CI, 2.4 to 5.2) more at risk for developing dementia before age 80 than relatives of control subjects. The hazard ratio in the subgroup with unknown linkage to chromosome 17 was 2.4 (95% CI, 1.5 to 3.7). This study documents the importance of genetic factors in a proportion of FTD patients with the age at onset of dementia in first-degree relatives being 11 years earlier than in the general population.

Vascular Risks and Incident Dementia: Results from a Cohort Study of the Very Old

The contribution of vascular pathology to the manifestation of dementia and the importance of vascular risk to measures of cognitive function is being increasingly recognized. In particular, confirmation of this risk points towards approaches for prevention in large sections of the population. Information on determinants of incident dementia is increasing, but still relatively few studies of risk have been based on incident cases of dementia in very elderly populations. In this study based on incident cases of dementia in a population aged 75 and over, vascular risks were obtained from informants of the respondents with incident dementia. When compared with controls the factors associated with incident dementia were history of heart attack (odds ratio 2.9), transient ischaemic attacks (4.8), cerebrovascular accidents (3.4), family history of first-degree relatives with dementia (4.0), and occupational exposure to vibrating instruments (1.4). If only Alzheimer’s disease, clinically diagnosed, was included, diabetes (1.4) and a history of dementia in first-degree relatives (6.6) emerged. Thus, vascular risk continues to be of importance in the oldest age groups.

Alzheimer's disease

We evaluated 197 patients with predominantly late-onset Alzheimer's disease (AD) who belonged to several ethnic groups and analyzed the relationship of age of onset of AD to the presence or absence of several risk factors in this entire group of patients. The apolipoprotein E (apoE) epsilon 4 allele frequency, which was 29% in all patients (compared with the reported population mean of 13.7%, p < 0.001, did not vary significantly between ethnic groups but declined significantly with increasing age. The apoE epsilon 2 allele frequency was 3%, compared with the reported population mean of 7.4% (p = 0.001). The frequency of a positive family history of dementia in first-degree relatives (FH +) (overall 45%) did not vary significantly between ethnic groups. ApoE epsilon 4-positive (epsilon 4+) patients tended to have a higher FH + rate (58%) than apoE epsilon 4-negative (epsilon 4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ status, and epsilon 4+ status were examined together in a multiple linear-regression analysis, FH+ and epsilon 4+ status (but not gender or education) were significant (they were both associated with an earlier age of onset of AD). In a post-hoc analysis, we found a reduced age of onset in women, but not men, who were both FH + and epsilon 4+. Additionally, those probands who were epsilon 4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which epsilon 4+ and FH+ status operate as risk factors may be by their effect on the age of onset of AD.

A case-control study of Alzheimer's disease in China.

We conducted a case-control study to assess possible factors associated with Alzheimer's disease (AD) with 70 clinically diagnosed AD patients and 140 age- and sex-matched nondemented neighborhood controls in China. Factors significantly associated with AD cases were family history of dementia in first-degree relatives, family history of psychotic disorders in first-degree relatives, and left-handedness/ambidexterity. A history of arthritis showed a significantly negative association with AD. Neither a family history for Down's syndrome, history of head trauma, nor other conditions that might support immune or viral hypotheses in AD were significantly associated with AD cases. These data support the role of familial/genetic factors in AD.

Risk of Dementia in First-Degree Relatives of Patients With Alzheimer's Disease and Related Disorders

First-degree relatives of patients with Alzheimer's disease (AD) are at greater risk for dementia when compared with the relatives of their healthy peers, but not when compared with the relatives of patients with Parkinson's disease. This may indicate that the risk of dementia in these relatives is not specific to AD or that these studies are biased. We obtained a family history and vital status information on each first-degree relative of patients attending a clinic and in a group of recruited healthy elderly subjects. Patients formed two groups: probable AD and other forms of dementia or cognitive disorders without dementia. The odds of dementia in first-degree relatives did not differ between patient groups. The odds of dementia in relatives of patients with probable AD or other forms of dementia was six times that in the relatives of the healthy elderly subjects. The cumulative incidence of dementia increased with age in the first-degree relatives of all subjects. Approximately 50% of the first-degree relatives of patients with AD were demented by age 91 years, but almost the same number of the other patient group's relatives were demented as well. That figure was never reached in the healthy elderly subject's relatives. Because the risk of dementia in first-degree relatives of patients with AD was similar to that for patients with other disorders, we cannot exclude the possibility that this is the result of selection and information biases. Our investigation implies that the increased risk of dementia may not be specific to relatives of patients with AD; the risk may also be increased in first-degree relatives of patients with other neurologic disorders.