Risk factors for reduced survival after traumatic brain injury: a 30-year follow-up study.

PRIMARY OBJECTIVE: To evaluate risk factors for reduced survival in subjects with traumatic brain injury (TBI). PARTICIPANTS AND METHODS: A retrospective follow-up of three decades included 192 subjects with TBI. Cognitive testing was carried out on average 2 years after the injury (at mean age of 39.0 years), during the years 1966-1972. Cox's regression and logistic regression analyses were used and the survival of the subjects was compared with the general population using the standardized mortality ratio (SMR). RESULTS: Reduced survival was significantly associated with age at injury (p < 0.001) and vocational outcome (p = 0.003). Vocational outcome in turn was associated with age (p = 0.010), TBI severity (p < 0.001), cognitive impairment (p = 0.010), later TBIs (p = 0.007) and alcohol abuse (p = 0.015). Mortality in the younger patient group (age at death <40 years) was higher than in the general population (SMR 4.50, 95% CI = 2.02-10.01). CONCLUSIONS: A reduced working ability, influenced by age-, injury- and lifestyle-related factors, is associated with long-term survival after TBI. The mortality among younger patients is high, a finding which should be considered when planning the care after TBI.

Estrogen + progestin therapy and cognition: a randomized placebo-controlled double-blind study.

AIMS: The use of hormone therapy (HT) is a relevant and topical issue in the treatment of menopausal symptoms in women. Information regarding the effects of combination treatment with estrogen and progesterone as well as treatment timing on cognitive function is lacking and was evaluated in healthy pre- and postmenopausal women. METHODS: Sixteen premenopausal (45-51 years) and 16 postmenopausal (58-70 years) women were randomly assigned to receive either estrogen + progestin therapy (HT) or placebo (PL) for six months. The study was double-blind. Cognitive performance was measured at baseline and follow up with tests of verbal and visuomotor functions, verbal and visual memory, and attention. RESULTS: In premenopausal women, cognitive attention, when compared to baseline, improved with HT but declined slightly with PL in the two-choice reaction time task (P = 0.049), while PL was associated with better performance in tests of shared attention (P = 0.024) and auditory attention (P < 0.05). In postmenopausal women, HT was associated with improved performance in verbal episodic memory (P = 0.024) and a minor decline in auditory attention (P = 0.025). CONCLUSIONS: HT, with estradiol valerate and norethisterone, in healthy women showed only minor effects on attention around the menopausal transition and on memory in postmenopause.

Attention and depressive symptoms in chronic phase after traumatic brain injury.

OBJECTIVE: To study whether attention deficits differ between TBI (traumatic brain injury) patients with and without depressive symptoms. METHOD: The study group (n = 61, mean age = 59 years) consisted of symptomatic TBI patients injured on average 30 years earlier. They were studied with a broad range of attention tasks including computerized methods. The patients were divided into those with depressive symptoms (n = 32) and those without (n = 29), according to the short form of the Beck depression scale with a cut-off score of 5. In addition, a diagnosis of major depression was applied according to the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) (n = 6). The groups with depression or depressive symptoms were compared with the non-depressed TBI patients and with an age- and education-matched healthy control group (n = 31). RESULTS: Cognitive methods that require flexibility (Trail making B, Card sorting, Word fluency) and working memory (Subtraction test) were sensitive to discriminate TBI patients without depressive symptoms from the control subjects (p < 0.001). Only a few methods were able to discriminate the TBI patients with depressive symptoms from those without (p < 0.001 for Simple reaction time, p < 0.003 for Vigilance test). The depressed TBI patients (assessed by SCAN) did not differ from the non-depressed TBI patients in attention functions. CONCLUSIONS: The results suggest that problems in complex attention processing are more specific to TBI, while slowness in simple psychomotor speed and impaired sustained attention may be mostly related to depressive symptoms in patients with chronic TBI sequelae.

Neurological symptoms and natural course of xeroderma pigmentosum.

We have prospectively followed 16 Finnish xeroderma pigmentosum (XP) patients for up to 23 years. Seven patients were assigned by complementation analysis to the group XP-A, two patients to the XP-C group and one patient to the XP-G group. Six of the seven XP-A patients had the identical mutation (Arg228Ter) and the seventh patient had a different mutation (G283A). Further patients were assigned to complementation groups on the basis of their consanguinity to an XP patient with a known complementation group. The first sign of the disease in all the cases was severe sunburn with minimal sun exposure in early infancy. However, at the time the diagnosis was made in only two cases. The XP-A patients developed neurological and cognitive dysfunction in childhood. The neurological disease advanced in an orderly fashion through its successive stages, finally affecting the whole nervous system and leading to death before the age of 40 years. Dermatological and ocular damage of the XP-A patients tended to be limited. The two XP-C patients were neurologically and cognitively intact despite mild brain atrophy as seen by neuroimaging. The XP-G patients had sensorineural hearing loss, laryngeal dystonia and peripheral neuropathy. The XP-C patients had severe skin and ocular malignancies that first presented at pre-school age. They also showed immunosuppression in cell-mediated immunity. Neurological disease appears to be associated with the complementation group and the failure of fibroblasts to recover RNA synthesis following UV irradiation, but not necessarily to the severity of the dermatological symptoms, the hypersensitivity of fibroblasts to UVB killing or the susceptibility of keratinocytes to UVB-induced apoptosis.

Outcome of traumatic brain injury after three decades--relationship to ApoE genotype.

Significant traumatic brain injury (TBI) is nearly always associated with cognitive deficits, but in a highly variable manner. Apolipoprotein E (ApoE) plays a pivotal role in CNS response to injury. To examine the association of ApoE genotype with long-term outcome in TBI patients, we determined the ApoE genotype from 61 TBI patients who had been injured over three decades earlier. All patients had been studied neuropsychologically after their injuries. The long-term outcome was evaluated with repeated neuropsychological testing and by applying various measures of everyday functioning and quality of life. After three decades, TBI patients with the ApoE epsilon4 allele showed significantly poorer general cognitive level than those without this allele. This decline was wholly accounted for by a subgroup of these patients who had developed incident or clinical dementia, while the majority of the ApoE epsilon4 positive patients showed no decline at all. The other outcome measures describing vocational, physical, or subjective symptom outcome did not show significant relationships to the ApoE genotype. A portion of the TBI patients with the ApoE epsilon4 allele seem to be at risk of long-term cognitive decline.

Estrogen therapy and cognition: a 6-year single-blind follow-up study in postmenopausal women.

The authors evaluated the effect of long-term hormone therapy (HT) on cognition in 60 postmenopausal women (aged 53 to 72 years) in a single-blind, 6-year follow-up study. The subjects were divided into three groups: non-HT users, continuous HT users, and irregular HT users. Measures of verbal and visuomotor skills, verbal and visual memory, and attention were used. All women had well-maintained cognitive performance. Long-term HT did not affect cognition, either for better or for worse.

Hormone treatment gives no benefit against cognitive changes caused by acute sleep deprivation in postmenopausal women.

The objective was to evaluate whether hormone therapy (HT) gives any benefit against the possible impairment of cognitive performance when challenged by acute sleep deprivation. Twenty postmenopausal women volunteered (age range 59-72 years, mean=64.4 years, SD=4.4): 10 HT users and 10 nonusers. Eleven young women served as a control group for the cognitive age effect (age range 20-26 years, mean age 23.1 years, SD=1.6). The subjects spent four consecutive nights at the sleep laboratory and were exposed to acute sleep deprivation of 40 h. Measures of attention (reaction speed and vigilance), alertness, and mood were administered every 2 h during the daytime and every hour during the sleep deprivation night. Postmenopausal women performed slower than young controls, whereas young controls made more errors. In HT users, the recovery night did not fully restore the performance in the simple and two-choice reaction time tasks, but in nonusers it did so. Sleep deprivation had a detrimental, yet reversible effect on vigilance in all groups. In all groups, sleepiness started to increase after 15 h of sleep deprivation and remained elevated in the morning after the recovery night. Prolonged wakefulness or HT had no effect on mood. In conclusion, sleep deprivation impaired cognitive performance in postmenopausal as well as young women. Postmenopausal women kept up their performance at the expense of reaction speed and young women at the expense of accuracy. One night was not enough for HT users to recover from sleep deprivation. Thus, HT gave no benefit in maintaining the attention and alertness during sleep deprivation.

MRI findings and Axis I and II psychiatric disorders after traumatic brain injury: a 30-year retrospective follow-up study.

We studied the association between psychiatric disorders and the presence and location of traumatic lesions on magnetic resonance imaging (MRI) in 58 patients, on average, 30 years after traumatic brain injury. Axis I psychiatric disorders that had begun after the injury were assessed with the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1), and Axis II disorders with the Structured Clinical Interview for DSM-III-R Personality Disorders. A 1.5-Tesla MRI scanner was used. One-third of the subjects had traumatic lesions visible on MRI. Only three psychiatric disorders, that is, delusional disorder, dementia, and the disinhibited type of organic personality syndrome, were significantly more common in subjects with contusions. Concerning the location of contusions, organic personality syndrome and its disinhibited subtype were associated with frontal lesions, and major depression was, surprisingly, inversely associated with temporal lesions. These results, which should be interpreted with caution due to the limited size of the study group, suggest that the majority of psychiatric disorders after traumatic brain injury are not closely related to the specific location or even the presence of contusions detectable with post-acute MRI.

Alexithymia after traumatic brain injury: its relation to magnetic resonance imaging findings and psychiatric disorders.

OBJECTIVE: People with traumatic brain injury (TBI) were studied to assess the prevalence of alexithymia and its relationship to magnetic resonance imaging (MRI) findings and psychiatric disorders. METHODS: Fifty-four participants, 67% men, were evaluated after a median of 30 years since TBI. A control group was matched for age, gender, and severity of depression. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20). In patients with TBI, axis I psychiatric disorders were assessed with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN, version 2.1), and axis II disorders with the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II). MRI examinations were carried out with a 1.5 T MRI scanner. RESULTS: Alexithymia was significantly more common in patients with TBI than in controls (31.5% versus 14.8%; odds ratio 2.64, 95% confidence interval 1.03-6.80). None of the variables representing TBI, ie, severity of TBI or the presence, laterality, or location of contusions on MRI, was associated with the TAS-20 total scores. Several current axis I and II psychiatric disorders, particularly organic personality syndrome, were connected to higher TAS-20 scores. CONCLUSION: Alexithymia is common, along with psychiatric disorders, in patients with TBI. Both of them may reflect dysfunction of the injured brain. In clinical practice, alexithymic features should be taken into consideration in psychosocial rehabilitation after TBI.

Cognitive functions in relation to MRI findings 30 years after traumatic brain injury.

OBJECTIVE: The aim of the study was to relate cognitive effects of a remote traumatic brain injury (TBI) to MRI findings and severity of injury. METHOD: Sixty-one patients were assessed on average 30 years after a TBI of variable severity. A comprehensive cognitive test battery was used to evaluate memory, executive functions and cognitive overall impairment. Multiple regression analyses were used to examine the relationships between cognitive variables and MRI volumetric findings (the volumes of the hippocampus and the lateral ventricles) and local contusions on MRI. Also, the effect of injury severity on cognitive outcome was evaluated. RESULTS: Reductions in hippocampal volumes and lateral ventricular enlargement were significantly associated with impaired memory functions, memory complaints and executive functions. Of the MRI parameters used, the best predictor for cognitive outcome was the volume of the lateral ventricle. There was only a modest relationship between severity of injury and cognitive performance. CONCLUSIONS: The results show that long-term memory impairments after TBI are associated with MRI volumetric measures. This suggests that the degree of diffuse injury leading to atrophic changes is prognostically more important than the initial severity of TBI.

Sleep deprivation, cognitive performance, and hormone therapy in postmenopausal women.

OBJECTIVE: To study the effects of sleep deprivation on cognitive performance in postmenopausal women and to evaluate whether hormone therapy (HT) has a modifying effect on coping. DESIGN: Twenty-six postmenopausal women, aged 58 to 72 years (mean 64 years), volunteered for the study (HT users, n = 16; nonusers, n = 10). They spent four consecutive nights in the sleep laboratory. The cognitive tests were performed three times: after the baseline night, after one night of sleep deprivation, and after the rebound night. The cognitive measures included visual episodic memory, visuomotor performance, verbal attention, and shared attention. RESULTS: The practice effect typically occurring in cognitive tests was blunted during sleep deprivation, which indicated deterioration of performance. At rebound, performance improved in visual episodic memory (immediate recall P < 0.01; delayed recall P < 0.05), visuomotor performance (P < 0.001), verbal attention (P < 0.0001), and shared attention (P < 0.05). HT users performed better than nonusers in the visual episodic memory test (P < 0.05) and in one of three subtests of shared attention (cancellation P = 0.040). Otherwise hormone therapy did not influence the results. CONCLUSIONS: In postmenopausal women, sleep deprivation impaired visual functions and attention. However, this effect was not prolonged because after one rebound night the performance was improved, compared with baseline. Hormone therapy did not modify the cognitive performance during sleep deprivation.

Associations between serum testosterone fall and cognitive function in prostate cancer patients.

Data on the association between cognition and testosterone levels in elderly men are inconclusive. Androgen deprivation therapy is commonly used in the treatment of prostate cancer with the aim of achieving castration levels of serum testosterone. The study group comprised 26 elderly men (mean age 65 years) with newly diagnosed prostate cancer. Cognitive testing was done at baseline and at 6 and 12 months on androgen deprivation therapy. Cognitive performances were evaluated using verbal, visuomotor, and memory tests as well as tests of processing speed and attention. Castration levels of testosterone were achieved in all patients by 6 months. Significant associations between cognitive performances and testosterone decline were documented: visuomotor slowing, slowed reaction times in some attentional domains including working memory and impaired hit rate in a vigilance test, impaired delayed recall and recognition speed of letters, but improvement in object recall. The results suggest selective associations between testosterone decline and cognition. Documentation of cognitive performance with changes in serum testosterone levels has substantial implications for informed patient support in prostate cancer.

Visual object recognition deficits in early Parkinson's disease.

The nature of the visual perception deficits in Parkinson's disease (PD) has remained unclear. The present study explored whether there emerge deficits in the different stages of visual object recognition in early PD. Twenty-eight patients and 14 healthy controls were studied. A set of reaction time tasks were applied to measure the different stages of object recognition. The results indicate some selective problems in both basic perceptual and semantic visual processing at an early stage of cognitive deterioration in PD.

Axis I and II psychiatric disorders after traumatic brain injury: a 30-year follow-up study.

OBJECTIVE: Patients who had suffered traumatic brain injury were evaluated to determine the occurrence of psychiatric disorders during a 30-year follow-up. METHOD: Sixty patients were assessed on average 30 years after traumatic brain injury. DSM-IV axis I disorders were diagnosed on a clinical basis with the aid of the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1), and axis II disorders were diagnosed with the Structured Clinical Interview for DSM-III-R Personality Disorders. Cognitive impairment was measured with a neuropsychological test battery and the Mini-Mental State Examination. RESULTS: Of the 60 patients, 29 (48.3%) had had an axis I disorder that began after traumatic brain injury, and 37 (61.7%) had had an axis I disorder during their lifetimes. The most common novel disorders after traumatic brain injury were major depression (26.7%), alcohol abuse or dependence (11.7%), panic disorder (8.3%), specific phobia (8.3%), and psychotic disorders (6.7%). Fourteen patients (23.3%) had at least one personality disorder. The most prevalent individual disorders were avoidant (15.0%), paranoid (8.3%), and schizoid (6.7%) personality disorders. Nine patients (15.0%) had DSM-III-R organic personality syndrome. CONCLUSIONS: The results suggest that traumatic brain injury may cause decades-lasting vulnerability to psychiatric illness in some individuals. Traumatic brain injury seems to make patients particularly susceptible to depressive episodes, delusional disorder, and personality disturbances. The high rate of psychiatric disorders found in this study emphasizes the importance of psychiatric follow-up after traumatic brain injury.