Tests Of Frontal Lobe Function Research Articles

The Effect of Transcranial Alternating Current Stimulation With Cognitive Training on Executive Brain Function in Individuals With Dementia: Protocol for a Crossover Randomized Controlled Trial.

BackgroundAlthough memory and cognitive declines are associated with normal brain aging, they may also be precursors to dementia.ObjectiveWe aim to offer a novel approach to prevent or slow the progress of neurodegenerative dementia, or plausibly, improve the cognitive functions of individuals with dementia.MethodsWe will recruit and enroll 75 participants (older than 50 years old with either mild cognitive impairment or probable early or moderate dementia) for this double-blind randomized controlled study to estimate the efficacy of active transcranial alternating current stimulation with cognitive treatment (in comparison with sham transcranial alternating current stimulation). This will be a crossover study; a cycle consists of sham or active treatment for a period of 4 weeks (5 days per week, in two 30-minute sessions with a half-hour break in between), and participants are randomized into 2 groups, with stratification by age, sex, and cognitive level (measured with the Montreal Cognitive Assessment). Outcomes will be assessed before and after each treatment cycle. The primary outcomes are changes in Wechsler Memory Scale Older Adult Battery and Alzheimer Disease Assessment Scale scores. Secondary outcomes are changes in performance on tests of frontal lobe functioning (verbal fluency), neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire), mood changes (Montgomery-Åsberg Depression Rating Scale), and short-term recall (visual 1-back task). Exploratory outcome measures will also be assessed: static and dynamic vestibular response using electrovestibulography, neuronal changes using functional near-infrared spectroscopy, and change in spatial orientation using virtual reality navigation.ResultsAs of February 10, 2022, the study is ongoing: 7 patients have been screened, and all were deemed eligible for and enrolled in the study; 4 participants have completed baseline assessments.ConclusionsWe anticipate that transcranial alternating current stimulation will be a well-tolerated treatment, with no serious side effects and with considerable short- and long-term cognitive improvements.Trial RegistrationClinicaltrials.gov NCT05203523; https://clinicaltrials.gov/show/NCT05203523International Registered Report Identifier (IRRID)DERR1-10.2196/37282

Neuropsychological outcomes after frontal lobectomy to treat intractable epilepsy

ObjectiveFrontal lobectomy is often used as a surgical treatment for frontal lobe epilepsy, especially when a large epileptogenic zone in the frontal lobe is inferred from preoperative evaluation. The frontal lobe is important for cognitive functions such as executive functions and verbal fluency, but the neuropsychological outcome after a frontal or prefrontal lobectomy that includes both the dorsolateral prefrontal cortex and ventral prefrontal cortex has not been studied thoroughly. In the present study, we evaluated neuropsychological outcomes after patients with frontal lobe epilepsy received a frontal or prefrontal lobectomy. MethodsWe retrospectively reviewed the data of patients with frontal lobe epilepsy who underwent a frontal or prefrontal lobectomy that includes both the dorsolateral prefrontal cortex and ventral prefrontal cortex at 16 years or older from October 2004 to December 2014, with a minimum postoperative follow-up of 24 months. We analyzed and compared neuropsychological outcomes, including executive functions, verbal fluency, intelligence, and memory, before and after the operation. ResultsEighteen patients were 16 years or older and underwent pre- and postoperative (2 years after the operation) neuropsychological evaluations. Patients showed significant deterioration only on the Benton Visual Retention Test. Performance on tests of frontal lobe functions, such as executive function and verbal fluency, showed no significant deterioration. ConclusionsOverall cognitive performance, including functions widely thought to depend on the frontal lobe, is stable after a frontal or prefrontal lobectomy to treat frontal lobe epilepsy.

Food memory test to evaluate memory function.

To evaluate cognitive function with ease at bedside, we developed a novel neurologic exam called the "food memory test (FMT)" and evaluated its validity for use in clinical practice. In this prospective study in a neurology clinic, we asked patients about what they had eaten for the soup and main dish at the last meal [FMT1] and the second-to-last meal [FMT2]. If they answered correctly for both the soup and main dish, they received a "pass" score. If they did not answer or chose the wrong food, they received a "fail" score. We also performed conventional cognitive function tests for comparison. A total of 27 patients was enrolled, and 12 (44.4%) passed the FMT1 test. FMT1 has a strong correlation with conventional memory function tests, including time-place orientation, three-word recall, the Seoul Verbal Learning Test, and the Rey Complex Figure Test . FMT1 was not correlated with a depression score or with frontal lobe function tests. FMT2 showed less significant correlation with conventional memory tests. These results suggest that FMT1 is a reliable bedside test to evaluate recent memory. Clinical application of FMT in daily clinical practice is warranted.

Repeated Transcranial Magnetic Stimulation for Improving Cognition in Patients With Alzheimer Disease: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial.

BackgroundAlzheimer disease has no known cure. As existing pharmacologic interventions only modestly slow cognitive decline, there is a need for new treatments. Recent trials of repetitive transcranial magnetic stimulation (rTMS) have reported encouraging results for improving or stabilizing cognition in patients diagnosed with Alzheimer dementia. However, owing to small samples and lack of a well-controlled double-blind design, the results to date are inconclusive. This paper presents the protocol for a large placebo-controlled double-blind study designed with sufficient statistical rigor to measure the efficacy of rTMS treatment in patients with Alzheimer dementia.ObjectiveThe objectives are to (1) recruit and enroll up to 200 eligible participants, (2) estimate the difference in treatment effects between active treatment and sham treatment, (3) estimate the difference in treatment effects between two doses of rTMS applications, (4) estimate the duration of treatment effects among responders to active rTMS treatment, and (5) estimate the effect of dementia severity on treatment outcomes among patients receiving active rTMS treatment.MethodsWe have designed our study to be a double-blind, randomized, placebo-controlled clinical trial investigating the short- and long-term (up to 6 months) benefits of active rTMS treatment at two doses (10 sessions over 2 weeks and 20 sessions over 4 weeks) compared with sham rTMS treatment. The study will include patients aged ≥55 years who are diagnosed with Alzheimer disease at an early to moderate stage and have no history of seizures and no major depression. The primary outcome measure is the change in the Alzheimer Disease Assessment Scale-Cognitive Subscale score from pretreatment to posttreatment. Secondary outcomes are changes in performance on tests of frontal lobe functioning (Stroop test and verbal fluency), changes in neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire), and changes in activities of daily living (Alzheimer Disease Co-operative Study-Activities of Daily Living Inventory). Tolerability of the intervention will be assessed using a modification of the Treatment Satisfaction Questionnaire for Medication. We assess participants at baseline and 3, 5, 8, 16, and 24 weeks after the intervention.ResultsAs of November 1, 2020, we have screened 523 individuals, out of which 133 were eligible and have been enrolled. Out of the 133 individuals, 104 have completed the study. Moreover, as of November 1, 2020, there has been no serious adverse event. We anticipate that rTMS will considerably improve cognitive function, with effects lasting up to 3 months. Moreover, we expect rTMS to be a well-tolerated treatment with no serious side effect.ConclusionsThis protocol design will allow to address both the rTMS active treatment dose and its short- and long-term effects compared with sham treatment in large samples.Trial RegistrationClinicalTrials.gov NCT02908815; https://clinicaltrials.gov/ct2/show/NCT02908815International Registered Report Identifier (IRRID)DERR1-10.2196/25144

Cognitive impairment and drug responsiveness in mesial temporal lobe epilepsy

ObjectivesMesial temporal lobe epilepsy (MTLE) is the most common form of partial epilepsies. Seizures of MTLE with hippocampal sclerosis (MTLE-HS) are typically resistant to antiepileptic drug (AED) therapy. Although memory disturbances in patients with MTLE-HS are expected, verbal attention and frontal lobe functions may also be impaired. We aimed to examine the relationship between the clinical features and cognitive functions of patients by comparing cognitive test scores of patients with MTLE with few seizures (drug-responsive group) and those with frequent seizures (pharmacoresistant group). MethodsSeventy-nine patients with MTLE-HS and 30 healthy controls were enrolled. Thirty-four patients were accepted as the drug-responsive group (DrG), and 45 patients were included in the pharmacoresistant group (PRG). Tests evaluating attention, memory, and executive functions were performed on all participants. ResultsForty-nine (62%) female and 30 (38%) male patients with MTLE-HS, and 14 (46.7%) female and 16 (53.3%) male controls participated in the study. The mean age of the patients and controls was 33.53 ± 9.60 (range, 18–57) years and 35.90 ± 7.98 (range, 18–56) years, respectively. Both the DrG and PRG showed poorer performances in tests evaluating memory and frontal lobe functions when compared with the control group (CG). Additionally, attention test results were significantly worse in the PRG than in the DrG. ConclusionIt is reasonable to say that increased seizure frequency is the main causative factor of verbal attention deficit due to the poorer attention test results in the PRG. Poor performances in memory and frontal lobe function tests of all patients with MTLE-HS emphasized the importance of the mutual connection between the temporal lobe and prefrontal cortices.

Frontal lobe cognitive functions and electroencephalographic features in juvenile myoclonic epilepsy

PurposeThe study aimed to examine the relationship between frontal lobe functions and interictal electroencephalography (EEG) discharge characteristics of patients with juvenile myoclonic epilepsy (JME). MethodThirty patients with JME who had EEG with asymmetrical generalized discharge (aEEG), 15 patients with JME who had EEG with symmetrical generalized discharge (sEEG), and 15 healthy controls were included in the study. To evaluate attention, the digit span and Corsi block tests were used; to evaluate memory, we applied verbal and visual memory tests; to evaluate frontal lobe functions, we used clock drawing, verbal fluency, the Stroop test, trail making, mental control, and antisaccadic eye movement tests as well as the continuous performance (CPT) tests. Ethical ConsiderationsThe research was approved by the Research Ethics Committee of the Bakirkoy Research and Training Hospital for Psychiatry, Neurology, Neurosurgery, with protocol number: 41340010/4891-262, date: 05.02.2013. ResultsThe mean age of the 45 patients with JME was 22.89 ± 6.77 years, and 34 (75.6%) were female. The age at onset of seizures and disease duration of the patients with JME was 15.56 ± 4.06 years (range, 9–26 years) and 7.20 ± 5.59 years (range, 1–25 years), respectively. All patients were under valproate (VPA) treatment, and the mean VPA dosage was 783.33 ± 379.14 mg/day. Patients with JME scored worse than the control group in attention, memory, and frontal lobe functions. In patients with aEEG, scores of attention, memory, and frontal lobe function tests were lower than in patients with sEEG; however, with the exception of CPT, they were not statistically significant. ConclusionCognitive functions in JME have been shown to be impaired. Furthermore, we concluded that the frontal lobe cognitive functions may be worse in patients with aEEG than in patients with sEEG. Further studies in patients with JME with aEEG abnormalities may lead to a better understanding of the pathophysiology of JME.

The value of frontal assessment battery in stroke patients

The aim of this study is to evaluate the value of Frontal Assessment Battery (FAB) compared with Mini-Mental State Examination (MMSE) for detecting frontal lobe dysfunction and evaluate the correlations between FAB and neurocognitive function test. Medical records of stroke patients underwent cognitive assessment including the FAB and MMSE were retrospectively reviewed and the patients divided into three groups; lesions involving frontal lobe cortex, lesions related with frontal subcortical circuit and other lesion groups. We compared the FAB and MMSE scores, especially frontal lobe function domain among these groups. A total of 186 patients with frontal lobe lesion had significantly lower total FAB score compared to other lesions with frontal subcortical circuit. In correlation with neurocognitive function test, FAB scores were more correlated with measures of high cognitive function and memory tests, such as trail making test A, card sorting test, digital span and visual span, than MMSE. Even after controlling MMSE scores, FAB scores were correlated with trail making test A, digital span and visual span tests. In scatterplots, there was a positive correlation between MMSE and FAB scores. When divided group by median MMSE score, high MMSE score group showed lower correlation with FAB compared to low MMSE score group ( Fig. 1 ). FAB showed better correlation with other frontal lobe function tests than MMSE, especially executive and memory functions domains. The FAB scores were proportional to MMSE scores and this correlation was more prominent in low MMSE score group. In patients with high MMSE scores, there may also be frontal dysfunction that cannot be detected with the MMSE score, therefore additional FAB testing should be performed. The FAB has screening value for frontal lobe function added to MMSE and can be used in clinical to detect cognitive impairment more specifically.

Microvascular Endothelial Function and Neurocognition Among Adults With Major Depressive Disorder

Cardiovascular risk factors (CVRFs) and endothelial dysfunction have been associated independently with poorer neurocognition in middle-aged adults, particularly on tests of frontal lobe function. However, to our knowledge, no studies have examined markers of microvascular dysfunction on neurocognition or the potential interaction between macro- and microvascular biomarkers on neurocognition in middle-aged and older adults with major depressive disorder (MDD). Participants included 202 adults with MDD who were not receiving mental health treatment. Microvascular endothelial function was assessed using a noninvasive marker of forearm reactive hyperemia velocity while macrovascular endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery. CVRFs were assessed using the Framingham Stroke Risk Profile and fasting lipid levels. A standardized neurocognitive assessment battery was used to assess three cognitive domains: executive function, working memory, and verbal memory. Greater microvascular dysfunction was associated with poorer neurocognition across all three domains. Microvascular function continued to predict verbal memory performance after accounting for background factors and CVRFs. Macro- and microvascular function interacted to predict working memory performance (F = 4.511, 178, p = 0.035), with a similar nonsignificant association for executive function (F = 2.731, 178, p = 0.095), with moderate associations observed between microvascular function and neurocognition in the presence of preserved FMD (r61 = 0.40, p = 0.001), but not when FMD was impaired (r63 = -0.05, p = 0.675). Greater microvascular dysfunction is associated with poorer neurocognition among middle-aged and older adults. This association was strongest in participants with preserved macrovascular function.

Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial

SummaryBackgroundIn the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures.MethodsWe did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348.FindingsBaseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·0001). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group (95% CI 0·2–2·3). The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 (95% CI 0·3–4·8; p=0·028). A treatment effect was not noted for any other outcomes.InterpretationTo our knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure. Although we found no effect of simvastatin on the other outcome measures, these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials.FundingThe Moulton Foundation, the Berkeley Foundation, the Multiple Sclerosis Trials Collaboration, the Rosetrees Trust, a personal contribution from A W Pidgley CBE, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University College London.

Executive Dysfunction in Patients with Putaminal Hemorrhage

The frontal-subcortical circuits link the specific areas of the frontal cortex to the striatum, basal ganglia, and thalamus. Disruption of the frontal-subcortical circuits may lead to cognitive impairment with frontal lobe features. The putamen is a central component of frontal-subcortical circuits. Although putaminal lesions presumably lead to cognitive and behavioral changes, studies on frontal lobe dysfunctions after putaminal stroke are scarce. There are no previous studies that systematically examined frontal lobe functions with a focal putaminal lesion. The objective of this study is to demonstrate whether putaminal hemorrhage causes frontal lobe dysfunction. Cognitive functions, including various aspects of frontal lobe functions, were systematically assessed in 15 patients with left- or right-sided putaminal hemorrhage 2 months after the onset and compared with healthy controls. Patients did not have signs of aphasia, apraxia, or spatial neglect. They performed significantly worse on tests of frontal lobe function, including Letter-Number Sequencing (U = 22, P < .001), lexical fluency (U = 30, P < .001), and motor series subtest (U = 45, P = .004) of the Frontal Assessment Battery. On the Wisconsin Card Sorting Test, patients performed significantly worse for "categories achieved" (U = 29.5, P < .001), "perseverative errors" (U = 25, P < .001), and "set loss" (U = 49, P = .008). None showed behavioral impairment. Isolated putaminal hemorrhage causes modest frontal lobe dysfunction without behavioral symptoms. Our findings indicate that isolated putaminal hemorrhage disrupts the dorsolateral-striato-pallido-thalamic circuits and causes executive dysfunction.

Older people experiencing homelessness show marked impairment on tests of frontal lobe function.

Reported rates of mild and moderate cognitive impairment in older people experiencing homelessness range from 5-80%. The objective of this study was to determine the prevalence and characteristics of cognitive impairment in older people experiencing homelessness in the inner city of Sydney, Australia. Men and women experiencing homelessness aged 45 years and over in the inner city were screened for cognitive impairment. Participants who scored 26 or below on the mini-mental state examination and/or were impaired on any one of the clock-drawing test, the verbal fluency test and the trail-making test, part B were then assessed with a semi-structured interview, including the 21-item Depression Anxiety Stress Scale and the 12-item General Health Questionnaire. Screening of 144 men and 27 women aged between 45 years and 93 years identified cognitive impairment in 78%. Subsequently, high rates of mental and physical illness were identified, and 75% of subjects who were cognitively impaired performed poorly on frontal lobe tests. The trail-making test, part B was the most sensitive measure of frontal function. This study demonstrated that a large majority of older people experiencing homelessness, in the inner city of a high-income country, showed impairment on tests of frontal lobe function, a finding that could have significant implications for any medical or psychosocial intervention.

The Behavioral Dyscontrol Scale-II with non-elderly veterans.

The Behavioral Dyscontrol Scale-II (BDS-II) is a unique test of frontal lobe function. Although the test was created for use in geriatric populations, it can add useful data to assessments of non-elderly patients. The original scoring system for the BDS was characterized by a low ceiling, limiting its use with higher functioning populations. The BDS-II scoring system was created to address this issue; however, new normative data were not published. This study used a non-elderly Veteran sample to compare the psychometric properties of the BDS and BDS-II scoring systems. The BDS-II showed improved psychometric properties (reductions in skewness and kurtosis) and was significantly more reliable than the BDS. Normative data using both the total sample, as well as the subsample of healthy individuals, are provided for clinical use.

Developmental changes in frontal lobe function during a verbal fluency task: A multi-channel near-infrared spectroscopy study

Near-infrared spectroscopy (NIRS) is commonly used to investigate continuous changes of brain activation and has excellent time resolution. Verbal fluency task (VFT) is widely used as a neuropsychological test of frontal lobe function. The aim of this study was to investigate normal developmental change in frontal lobe function during VFT performance using multi-channel NIRS, specifically focusing on oxygenation hemoglobin (oxyHb) changes. The subjects were 9 adults and 37 childrens who were all healthy right-handed volunteers. Children were divided into four age groups (group A, 6-8 years; group B, 9-11 years; group C, 12-14 years; group D, 15-18 years). The [oxyHb] changes were measured with 22 channels of NIRS during VFT. We defined the frontopolar region as the region of interest for analysis, and calculated the Z-score to compare the data between groups. The task performance changed with age. There were significant differences between group A and other groups. The Z-score of [oxyHb] also significantly increased with age, when comparing adults to groups A and B. The task performances decreased with time in all groups. In contrast, [oxyHb] only continued to increase in the adult group. The verbal retrieval functions begin to mature in early adolescence and continue to grow up to adulthood.

Resting-state brain connectivity in patients with Parkinson's disease and freezing of gait

BackgroundFreezing of gait is a common cause of disability and falls in patients with Parkinson's disease. We studied brain functional connectivity, by means of resting-state functional magnetic resonance imaging, in patients with Parkinson's disease and freezing of gait. MethodsResting-state functional magnetic resonance imaging at 3 T was collected in 29 patients with Parkinson's disease, of whom 16 presented with freezing of gait as determined by a validated freezing of gait questionnaire, and 15 matched healthy controls. Single-subject and group-level independent component analysis was used to identify the main resting-state networks differing between Parkinson's disease patients with and without freezing of gait. Statistical analysis was performed using BrainVoyager QX. ResultsBetween-group differences in resting-state networks revealed that patients with freezing of gait exhibit significantly reduced functional connectivity within both “executive-attention” (in the right middle frontal gyrus and in the angular gyrus) and visual networks (in the right occipito-temporal gyrus) [p < 0.05 corrected for multiple comparisons]. Freezing of gait clinical severity was significantly correlated with decreased connectivity within the two networks. Consistent with their “executive-attention” network impairment, patients with freezing of gait scored lower on tests of frontal lobe functions (phonemic verbal fluency: p = 0.005; frontal assessment battery: p < 0.001; ten point clock test: p = 0.04). ConclusionsOur findings suggest that a resting-state functional connectivity disruption of “executive-attention” and visual neural networks may be associated with the development of freezing of gait in patients with Parkinson's disease.

Impaired Design Fluency Is a Marker of Pathological Cognitive Aging; Results from the Korean Longitudinal Study on Health and Aging

ObjectiveWe investigated neuropsychological markers that can be used to discriminate pathological cognitive aging from normal cognitive aging.MethodsWe administered frontal lobe function tests including the Wisconsin Card Sorting Test (WCST), digit span test, lexical fluency test, fixed condition design fluency test, and Trail Making Test B (TMT-B) to 92 individuals with pathological cognitive aging (PCA) and 222 individuals with normal cognitive aging (NCA). We examined the main effects of participants' diagnoses (PCA, NCA) and age (65-69 years old, 70-74 years old and 75 years old or over) on their test performance using multivariate analysis of variance.ResultsThe main effects of both the diagnosis (F=2.860, p=0.002) and the age group (F=2.484, p<0.001) were significant. The PCA group showed lower performance on the backward digit span test (F=14.306, p<0.001), fixed condition design fluency test (F=8.347, p=0.004) and also exhibited perseverative errors in the WCST (F=4.19, p=0.042) compared with the NCA group. The main effect of the diagnosis on the backward digit span test and the fixed condition design fluency test remained significant after Bonferroni correction. The main effect of age remained significant in the TMT-B (F=8.737, p<0.001) after Bonferroni correction. Other test scores were not influenced by diagnosis or age.ConclusionThe design fluency task may be a good neuropsychological marker to assess pathological cognitive aging.

Should We Listen to People Affected by Dementia?

Should We Listen to People Affected by Dementia?

Autonomic activity changes in frontal lobe function tests in young adults with high-functioning pervasive developmental disorder

Autonomic activity changes in frontal lobe function tests in young adults with high-functioning pervasive developmental disorder

Association between dysarthria and cognitive impairment in ALS: A prospective study

Several studies have demonstrated impaired cognition in amyotrophic lateral sclerosis (ALS) patients, but it has been difficult to identify risk factors for this impairment. An association between cognitive changes and bulbar site of onset or dysarthria has been suggested, but the findings are variable. We tested for both associations in a large cohort of ALS patients. At the time of diagnosis of sporadic ALS, all patients (n=355) in this prospective study underwent comprehensive neuropsychological testing. In addition, a subset of 175 patients underwent a detailed assessment of dysarthria, which was quantified using the Appel ALS Score (AALSS). ALS patients with bulbar site of onset performed significantly worse than limb onset patients on a few timed ((VSAT-time, p<0.05), (Stroop Color, p<0.05), (Stroop Word, p<0.05)) tests of frontal lobe functions, but the significance could not be replicated when motor impairment was accommodated into the tests ((VSAT-errors, p=0.73), (Stroop interference, p=0.08)). ALS patients with dysarthria performed significantly worse than non-dysarthrics on multiple timed ((BD, p<0.05), (VSAT-time, p<0.05), (Stroop Color, p<0.05), (Stroop Word, p<0.05), (Trails A, p<0.05), (Trails B, p<0.05)) neuropsychological tests, and the significance was maintained when motor impairment was accommodated into one of these tests (Stroop interference, p<0.05). Additionally, dysarthrics performed significantly worse on two untimed measures of cognition ((Similarities, p<0.05), (Rey Copy, p<0.05)). Cognitive functioning in ALS does not associate with the site of onset and has a moderate association with dysarthria.

Endogenous oestrogens predict 4‐year decline in verbal fluency in postmenopausal women: the Rancho Bernardo Study

Despite overwhelming biological plausibility, evidence for a protective effect of oestrogen on cognitive function in postmenopausal women is inconsistent. This study examines the association between endogenous oestrogen levels and subsequent 4-year decline in cognitive function test performance in community-dwelling older women. Longitudinal cohort study. Three hundred and forty-three postmenopausal women (median age 70 years). Between 1984 and 1987, serum for measurement of sex hormones was obtained along with relevant covariates. Cognitive function was assessed in 1988-1991 and again in 1992-1996 using the Category Fluency test, the Mini-Mental Status Exam (MMSE) and Trail Making Test B (Trails B). Women in the highest tertile of oestrone and bioavailable oestradiol had respectively 1.75 (95% CI 1.02, 3.07) and 1.79 (95% CI 1.04, 3.10) higher odds of 4 year decline in Category Fluency, a test of frontal lobe function, compared to those in the lowest tertile, independent of age and education. The 20% of women with highest tertile levels of both oestrone and bioavailable oestradiol had a twofold higher odds of verbal fluency loss (OR = 2.17; 95% CI 1.21, 3.89). Adjustment for testosterone levels or for obesity-related factors associated with high endogenous oestrogens (higher body mass index, waist girth, and triglycerides and lower high-density lipoprotein cholesterol) did not alter results. Neither oestrogen was associated with change in MMSE or Trails B scores. Higher endogenous oestrogen levels were associated with a greater decline in verbal fluency in postmenopausal women. This association was not explained by elevated androgens or by obesity or obesity-related factors.

Relationship of Striatal Dopamine Synthesis Capacity to Age and Cognition

Past research has demonstrated that performance on frontal lobe-dependent tasks is associated with dopamine system integrity and that various dopamine system deficits occur with aging. The positron emission tomography (PET) radiotracer 6-[(18)F]fluoro-l-m-tyrosine (FMT) is a substrate of the dopamine-synthesizing enzyme, aromatic amino acid decarboxylase (AADC). Studies using 6-[(18)F]fluorodopa (FDOPA) (another AADC substrate) to measure how striatal PET signal and age relate have had inconsistent outcomes. The varying results occur in part from tracer processing that renders FDOPA signal subject to aspects of postrelease metabolism, which may themselves change with aging. In contrast, FMT remains a purer measure of AADC function. We used partial volume-corrected FMT PET scans to measure age-related striatal dopamine synthesis capacity in 21 older (mean, 66.9) and 16 younger (mean, 22.8) healthy adults. We also investigated how striatal FMT signal related to a cognitive measure of frontal lobe function. Older adults showed significantly greater striatal FMT signal than younger adults. Within the older group, FMT signal in dorsal caudate (DCA) and dorsal putamen was greater with age, suggesting compensation for deficits elsewhere in the dopamine system. In younger adults, FMT signal in DCA was lower with age, likely related to ongoing developmental processes. Younger adults who performed worse on tests of frontal lobe function showed greater FMT signal in right DCA, independent of age effects. Our data suggest that higher striatal FMT signal represents nonoptimal dopamine processing. They further support a relationship between striatal dopamine processing and frontal lobe cognitive function.