Risk of dementia associated with the ApoE epsilon4 allele and falls causing head injury without explicit traumatic brain injury.

OBJECTIVES: Severe head injury (HI) and the apolipoprotein E (ApoE) epsilon4 allele are risk factors for dementia. The corresponding effect of falls causing HI without explicit traumatic brain injury (TBI) in association with the ApoE epsilon4 is not known. MATERIALS AND METHODS: Altogether 134 persons aged 70 years or older constituted a retrospective population sample, who scored > or =26 in the MiniMental State Examination (MMSE) test at baseline and were clinically examined for dementia 9 years afterward. Fall-related HI causing superficial laceration or bruises or wounds that require suturing were prospectively recorded during the 9-year follow-up. We used Cox regression with age at the diagnosis of dementia as a dependent variable. RESULTS: Twenty-eight (21%) subjects had falls causing HI without explicit TBI, the ApoE epsilon4 allele was seen in 44 (33%), and clinical dementia was diagnosed in 25 (19%). Adjusted for the baseline MMSE score, sex and educational status, the hazard ratio for subsequent dementia in subjects having falls with HI without explicit TBI and the ApoE epsilon4 allele as compared with those who do not possess these characteristics was 2.70 (95% confidence interval, 1.02-7.16). CONCLUSIONS: According to the results of this small retrospective study, falls with HI without explicit TBI in connection with the ApoE epsilon4 allele is associated with subsequent dementia among older adults.

The common MELAS mutation A3243G in mitochondrial DNA among young patients with an occipital brain infarct.

The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) may present with symptoms that resemble a stroke. The strokelike episodes most commonly involve the posterior part of the cerebrum. We identified retrospectively 38 patients with an occipital stroke between ages 18 to 45 years during a 19-year period in a hospital serving as the only neurologic center for a specific population. The common MELAS mutation at the base pair 3243 (A3243G) of the mitochondrial DNA (mtDNA) was analyzed in blood samples. We found four patients (10%) with a clinical or molecular diagnosis of a mitochondrial disorder. Two of the patients carried the A3243G mutation, suggesting frequencies of 6% among patients younger than 45 years of age and 14% among patients younger than 30 years for this mutation. Furthermore, we identified two patients with a clinically definite mitochondrial disorder, and sequencing of the 22 transfer RNA genes revealed the mtDNA mutation A12308G in one patient. Clinical evaluation revealed that occipital stroke was part of a more complex syndrome in these four patients. These population-based findings demonstrate that the A3243G mutation in the mtDNA, and mitochondrial disorders are not uncommon among young patients with occipital stroke.

Ubiquinone and nicotinamide treatment of patients with the 3243A-->G mtDNA mutation.

The efficacy and safety of ubiquinone (Q10) and nicotinamide were evaluated in a 6-month open-label trial in patients with the 3243A-->G mitochondrial DNA mutation. Blood lactate and pyruvate concentrations decreased, but there was little clinical improvement. Q10 and nicotinamide were well tolerated, but two patients died suddenly and unexpectedly during the trial. These deaths may have been unrelated to treatment. The unpredictable course of the disease makes evaluation of the clinical response difficult.

A 3-year clinical follow-up of adult patients with 3243A>G in mitochondrial DNA.

OBJECTIVE: To follow the clinical course of patients with the mitochondrial DNA mutation 3243A>G for 3 years. METHODS: Thirty-three adult patients with the 3243A>G mutation entered a 3-year follow-up study. They were clinically evaluated annually, audiometry was performed, and samples were drawn for the analysis of blood chemistry and mutation heteroplasmy in leukocytes. Holter recording was performed three times during the follow-up and echocardiography, neuropsychological assessment, and quantitative EEG and brain imaging conducted at entry and after 3 years. RESULTS: The incidence of new neurologic events was low during the 3-year follow-up. Sensorineural hearing impairment (SNHI) progressed, left ventricular wall thickness increased, mean alpha frequency in the occipital and parietal regions decreased, and the severity of disease index (modified Rankin score) progressed significantly. The rate of SNHI progression correlated with mutation heteroplasmy in muscle. The increase in left ventricular wall thickness was seen almost exclusively in diabetic patients. Seven patients died during the follow-up, and they were generally more severely affected than those who survived. CONCLUSIONS: Significant changes in the severity of disease, sensorineural hearing impairment, left ventricular hypertrophy, and quantitative EEG were seen in adult patients with 3243A>G during the 3-year follow-up.

Fall-related brain injuries and the risk of dementia in elderly people: a population-based study.

Severe head injury in early adulthood may increase the risk of dementia in older age, but it is not known whether head injury in later life also increases the risk of dementia. A representative sample (82%) of persons aged 70 years or older with a Mini-Mental State Examination (MMSE) test score of > or =26 (n = 325) were followed-up for 9 years to record all their fall-related head injuries resulting in traumatic brain injury (TBI). At the end of the follow-up period, 152 persons (81% of the surviving population) were examined for clinical dementia, according to DSM-IV criteria. Eight persons sustained a TBI and 34 developed dementia. Brain injury was associated with younger age at detection of dementia even when adjusted for sex and educational status (low educational status significantly associated with dementia); age-specific hazard ratio (95% confidence interval) 2.80 (1.35-5.81). In a population scoring > or =28 points in the baseline MMSE an apolipoprotein E (ApoE) epsilon4 phenotype was also associated with younger age at the time of detecting dementia; 3.56 (1.35-9.34), and the effect of brain injury and ApoE epsilon4 phenotype was synergistic; 7.68 (2.32-25.3). We conclude that fall-related TBI predicts earlier onset of dementia and the effect is especially high amongst subjects who carry the ApoE epsilon4 allele.

Physical and psychosocial outcome for young adults with treated malignancy.

We reexamined the physical, neurological, neuropsychological, social, and psychiatric circumstances of a group of 27 (10 females, 17 males) patients at the ages of 16-26 years who had survived a malignant disease during childhood. Twenty survivors had had leukemia and the rest different solid tumors. Only a third (31%) of the subjects were considered to be without any clinically significant physical health problems or functional symptoms, musculoskeletal and endocrinological disorders being the most common. In the neuropsychological test panel including verbal and performance IQ the survivors had significantly lower scores. Early onset of the disease and receiving radiotherapy correlated with impaired test results most significantly, especially on memory functions. One in five of the survivors reported having suffered from reading and writing problems that interfered with success in school and the subjects of the study group had progressed to high school less often than control subjects. The social indices indicated delayed development of sexuality and separation from parents. Overt mental problems appearing at a one-off interview were the same as in the control group. In conclusion, up to two thirds of the childhood cancer survivors as young adults still have physical or neuropsychological health problems and half showed delayed psychosexual maturation. This magnitude of various disorders indicates a long-term but individually oriented follow-up of this small group with the opportunity of physical, social, or psychological management of their main problem.

Cognitive functions of young adults who survived childhood cancer.

Neuropsychological tests were used to determine the cognitive functioning of adult long-term survivors treatedfor childhood cancer Disease onset before the age of 5 was related to lower test scores in intelligence tests, several memory tests, and motor function tests. The cranial irradiated survivors displayed more difficulties, especially in short-term memory tests and the Wechsler Adult Intelligence Scale Digit Symbol Test as compared to nonradiated survivors. No statistically significant differences in test scores were observed between different forms of cancer The results of this study are consistent with the notion that those memory types that demand special attention and motor speed functions are especially vulnerable to cancer and its treatment.