Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer.

OBJECTIVE: Androgen deprivation therapy (ADT) is a common treatment option for men with biochemical relapse from prostate cancer. ADT is associated with changes in mood, cognition, and quality of life, and most recently with increased risk for Alzheimer's disease (AD). This study examined changes in brain metabolism using positron emission tomography (PET) in men undergoing intermittent ADT. METHODS: Nine men with prostate cancer and a rising PSA (biochemical recurrence) without evidence of metastases were treated with intermittent ADT consisting of 9 months of complete androgen blockade achieved with combined leuprolide acetate and flutamide. Patients underwent resting [Fuorine-18] fluorodeoxyglucose PET (18F-FDGPET) at baseline (before treatment) and again after 9 months of ADT. RESULTS: Whole-brain mapping analysis after 9 months of androgen deprivation compared to pretreatment baseline revealed decreased regional cerebral glucose metabolism in the cerebellum, posterior cingulate, and medial thalamus bilaterally. Associations of brain metabolism with measurements of cognition and mood while on androgen deprivation revealed positive correlations between the posterior cingulate, left inferior parietal lobule (BA40), and left mid temporal gyrus (BA39) and spatial reasoning and a negative correlation between left inferior parietal lobule and verbal memory. Several mood indices were negatively correlated with hypothalamus and brainstem. CONCLUSION: These findings suggest that complete androgen deprivation may result in changes in regional brain metabolism associated with variation in mood, verbal memory, and spatial performance. Brain regions that were impacted from ADT are similar and overlap with brain regions with metabolic decline found in early AD and diabetes, suggesting possible common mechanisms.

Testosterone treatment of men with mild cognitive impairment and low testosterone levels.

INTRODUCTION: This study investigated the effects of testosterone (T) treatment on cognition, mood, and quality of life in men with mild cognitive impairment (MCI) and low serum T levels. METHODS: A total of 351 community-dwelling men were screened, and 37 men evidenced both MCI and low T of whom 27 agreed for further screening. Twenty-two met all the study inclusion/exclusion criteria and enrolled in a 6-month randomized, double-blind, placebo-controlled study. RESULTS: Total T levels significantly increased in the T treatment group. No significant changes were observed in measures of cognition, mood, or quality of life other than improvement in 1 objective measure of verbal memory (P < .05) and decreased depression symptoms (P < .02) in the treatment group. CONCLUSIONS: Testosterone treatment may modestly improve verbal memory and depression symptoms in men with both MCI and low T.

A randomized trial of cognitive rehabilitation in cancer survivors.

AIMS: The second most frequently reported post-treatment symptom in cancer survivors are concerns about impaired cognition. Despite numerous studies demonstrating significant impairments in a portion of survivors, information on effective treatments remains an emerging area of research. This study examined the effectiveness of a group-based cognitive rehabilitation intervention in cancer survivors. MAIN METHODS: This study was a randomized, controlled study of a 7-week cognitive rehabilitation intervention delivered in group format. Participants were evaluated with subjective symptom questionnaires and objective neurocognitive tests prior to and following treatment. KEY FINDINGS: Twenty-eight participants (mean age 58 years) with a median of 3 years (± 6 years) post-primary/adjuvant treatment and various cancer sites (breast, bladder, prostate, colon, uterine) completed the study. Compared to baseline, the treatment group demonstrated improvements in symptoms of perceived cognitive impairments (p<.01), cognitive abilities (p<.01) and overall quality of life with regard to cognitive symptoms (p<.01) as measured by the FACT-Cog. The treatment group also improved on objective measures of attention (p<.05) and a trend toward improvement on verbal memory. Significant improvement was not observed on all cognitive tests. SIGNIFICANCE: A group based cognitive rehabilitation intervention in cancer survivors was effective for improving attention abilities and overall quality of life related to cognition. Results suggest that group based cognitive rehabilitation may be an effective intervention for treating cognitive dysfunction in cancer patients and should be further studied in a larger trial with an active control condition.

Cognitive and mood changes in men undergoing intermittent combined androgen blockade for non-metastatic prostate cancer.

PURPOSE: Men with prostate-specific antigen (PSA)-only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to 10 or more years. Androgen deprivation therapy (ADT) is a common treatment option. This study examined mood and cognitive changes in otherwise healthy men with prostate cancer prior to, during and after ADT. EXPERIMENTAL DESIGN: Twenty hormone naïve, eugonadal prostate cancer patients without evidence of metastases and with a rising PSA were treated with intermittent ADT consisting of 9 months of complete androgen blockade (CAB) achieved with combined leuprolide and flutamide followed by an 'off treatment' period. Cognitive function tests and mood measures were administered at baseline, after 3 and 9 months of ADT and after 3 months of no treatment. Twenty healthy control patients without prostate cancer range matched for age and education were tested at the same time intervals. RESULTS: ADT patients evidenced a significant decline in spatial reasoning, spatial abilities and working memory during treatment compared with baseline. No changes were noted for measures of verbal or spatial memory, selective attention or language. Significant changes in self-rated mood such as increased depression, tension, anxiety, fatigue and irritability were evident during treatment compared with baseline for ADT patients. No significant changes in either cognitive tests or mood measures were noted for the healthy control group. CONCLUSIONS: These findings, suggest that 9 months of combined androgen blockade may result in some adverse changes in cognition and mood. However, many but not all of these changes can return to baseline after cessation of ADT.

Characterization of verbal and spatial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men.

BACKGROUND: It has been suggested that cognitive changes in response to T supplementation may occur within an ideal range. The objective of this study was to compare the cognitive responses of older, eugonadal men in whom moderate or large increases in serum testosterone levels was induced by exogenous testosterone supplementation. DESIGN: Randomized, double-blind, placebo-controlled study with subsequent grouping of participants according to average increase in circulating T from baseline. SETTING: Community dwelling participants. PARTICIPANTS: Fifty-seven healthy, eugonadal, community dwelling male volunteers, mean age 67 years (+/-11 years). INTERVENTIONS: Participants were randomized to receive weekly intramuscular (i.m.) injections of either 50, 100 or 300 mg T enanthate or placebo (saline) injection for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, weeks 3 and 6 of treatment and after 6 weeks of wash-out. MAIN OUTCOME MEASURES: Performance on cognitive tests of verbal and spatial memory. RESULTS: Men with moderate increases in serum T and/or its metabolites demonstrated significant improvements in verbal and spatial memory. In contrast, men with large or low increases in circulating T levels, failed to demonstrate significant changes in memory. CONCLUSION: These results suggest that in healthy older men, beneficial changes in cognitive function induced by T supplementation are most evident with moderate changes in cognition from moderate to high T supplementation increases in T levels. Large or no to low increases in T levels do not appear to appreciably effect cognition.

Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype.

Raising insulin acutely in the periphery and in brain improves verbal memory. Intranasal insulin administration, which raises insulin acutely in the CNS without raising plasma insulin levels, provides an opportunity to determine whether these effects are mediated by central insulin or peripheral processes. Based on prior research with intravenous insulin, we predicted that the treatment response would differ between subjects with (epsilon4+) and without (epsilon4-) the APOE-epsilon4 allele. On separate mornings, 26 memory-impaired subjects (13 with early Alzheimer's disease and 13 with amnestic mild cognitive impairment) and 35 normal controls each underwent three intranasal treatment conditions consisting of saline (placebo) or insulin (20 or 40 IU). Cognition was tested 15 min post-treatment, and blood was acquired at baseline and 45 min after treatment. Intranasal insulin treatment did not change plasma insulin or glucose levels. Insulin treatment facilitated recall on two measures of verbal memory in memory-impaired epsilon4- adults. These effects were stronger for memory-impaired epsilon4- subjects than for memory-impaired epsilon4+ subjects and normal adults. Unexpectedly, memory-impaired epsilon4+ subjects showed poorer recall following insulin administration on one test of memory. These findings suggest that intranasal insulin administration may have therapeutic benefit without the risk of peripheral hypoglycemia and provide further evidence for apolipoprotein E (APOE) related differences in insulin metabolism.

Androgens and cognitive function.

Decrements in cognitive functioning are a common complaint among men with late-onset hypogonadism (LOH). This article reviews the neurobiologic connection between gonadal steroids and cognitive functions, developmental effects and activational effects throughout the lifespan. Studies of hormone replacement therapy in older men are reviewed as well as epidemiological studies of endogenous hormones and cognition. While many studies of Androgen Replacement Therapy (ART) in older men suggest a potential beneficial effect on cognition, most studies to date have been small and need further replication with larger sample sizes.

Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment.

OBJECTIVE: To determine the efficacy of testosterone (T) supplementation on cognition in a sample of men with Alzheimer disease (AD) or mild cognitive impairment (MCI). METHODS: Fifteen patients with AD and 17 patients with MCI aged 63 to 85 years completed a randomized, double-blind, placebo-controlled study. Nineteen participants received weekly intramuscular (IM) injections of 100 mg T enanthate and 13 participants received weekly injections of placebo (saline) for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, week 3, and week 6 of treatment and again after 6 weeks of washout. RESULTS: Peak serum total T levels were raised from baseline an average of 295% in the active treatment group. Improvements in spatial memory (p < 0.05) and constructional abilities (p < 0.05) and verbal memory were evident in the T group. No changes were noted for selective and divided attention or language. Prostate specific antigen did not significantly change during this brief treatment. CONCLUSION: Testosterone supplementation may benefit selective cognitive functions in men with Alzheimer disease and mild cognitive impairment.

Cognitive differences in dementia patients with autopsy-verified AD, Lewy body pathology, or both.

OBJECTIVE: To examine the neuropsychological profile of dementia patients from a community-based autopsy sample of dementia, comparing Alzheimer disease (AD), Lewy body pathology (LBP) alone, and LBP with coexistent AD (AD/LBP). METHODS: The authors reviewed 135 subjects from a community-based study of dementia for whom autopsy and brain tissue was available. Diagnostic groups were determined according to standard neuropathologic methods and criteria, and the presence of LBs was determined using alpha-synuclein immunostaining. Neuropathologically defined diagnostic groups of AD, AD/LBP, and LBP were examined for differences on neuropsychological test performance at the time of initial study enrollment. RESULTS: There were 48 patients with AD alone, 65 with LB and AD pathology (AD/LBP), and 22 with LBP alone (LBP alone). There were no significant differences between groups demographically or on performance of enrollment Mini-Mental State Examination (MMSE) or Dementia Rating Scale (DRS). AD patients performed worse than the LBP patients on memory measures (Fuld Object Memory Evaluation Delayed Recall, Wechsler Memory Scale Logical Memory Immediate and Delayed Recall; p < 0.05) and a naming task (Consortium to Establish a Registry for Alzheimer's Disease Naming; p < 0.05). LBP patients were more impaired than AD patients on executive function (Trail Making Test Part B; p < 0.05) and attention tasks (Wechsler Adult Intelligence Scale-Revised Digit Span; p < 0.05). Decline in MMSE and DRS scores over time were greatest in the patients with AD/LBP. CONCLUSIONS: In a community-based sample of older, medically complicated patients with dementia, there are neuropsychological differences between dementia subtypes at the time of diagnosis. In particular, patients with Alzheimer disease (AD) alone and AD/Lewy body pathology (LBP) had more severe memory impairment than patients with LBP. LBP alone was associated with more severe executive dysfunction. Patients with AD/LBP had the most rapid rate of cognitive decline.

The role of aromatization in testosterone supplementation: effects on cognition in older men.

OBJECTIVE: To determine the contribution of conversion of testosterone (T) to estradiol on cognitive processing in a population of healthy older men who received T supplementation. METHODS: Sixty healthy, community-dwelling volunteers aged 50 to 90 years completed a randomized, double-blind, placebo-controlled study. Participants were randomized to receive weekly IM injections of 100 mg T enanthate plus daily oral placebo pill (T group, n = 20), 100 mg testosterone enanthate plus 1 mg daily of anastrozole, an aromatase inhibitor (oral pill), to block the conversion of T to estradiol (AT group, n = 19), or saline injection and placebo pill (placebo group, n = 21) for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, week 3 and week 6 of treatment, and after 6 weeks of washout. RESULTS: Circulating total T was increased from baseline an average of 238% in the T and AT treatment groups. Estradiol increased an average of 81% in the T group and decreased 50% in the AT group during treatment. Significant improvements in spatial memory were evident in the AT and T treatment groups. However, only the group with elevated estradiol levels (T group) demonstrated significant verbal memory improvement. CONCLUSION: In healthy older men, improvement in verbal memory induced by testosterone administration depends on aromatization of testosterone to estradiol, whereas improvement in spatial memory occurs in the absence of increases in estradiol.

Relationship between testosterone supplementation and insulin-like growth factor-I levels and cognition in healthy older men.

BACKGROUND: Our laboratory has previously reported that testosterone (T) administration to older men significantly improves cognitive function. This study examined potential changes in insulin-like growth factor (IGF) IGF-I, IGF-II and IGF-related binding proteins in response to T administration in older men and their relationship to cognitive functioning. METHODS: Twenty-five healthy community dwelling volunteers, ranging in age from 50-80 years were randomized to receive weekly intra-muscular (i.m.) injections of either 100 mg T enanthate or placebo (saline) for 6 weeks. Serum hormone levels and cognitive functioning was assessed at baseline and twice during treatment. RESULTS: Significant positive associations between IGF-I and IGF-II and spatial memory, spatial reasoning, and verbal fluency were observed after 6 weeks of T administration. Increased serum T levels from treatment were positively associated with improvement in spatial reasoning performance, whereas estradiol was associated with a decline in divided attention performance. Serum IGF-I, IGF-II and IGFBPs did not change in response to T treatment. CONCLUSIONS: Our results suggest that T, estradiol and IGF-I may have independent and selective effects on cognitive functioning. Positive associations between T levels and cognition are consistent with an effect of androgen treatment, whereas positive associations between IGF-I levels and cognition are reflective of a relationship between endogenous IGF-I levels and cognition.

The effects of combined androgen blockade on cognitive function during the first cycle of intermittent androgen suppression in patients with prostate cancer.

PURPOSE: Men with prostate specific antigen (PSA) only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to 10 or more years. These patients are often treated with androgen suppression. We evaluate the effects of androgen suppression on cognitive function. MATERIALS AND METHODS: Hormone naïve patients without evidence of metastases with an increasing PSA were treated with intermittent androgen suppression consisting of 9 months of leuprolide and flutamide followed by an off treatment period determined by the increase in PSA. Cognitive function tests were administered at baseline, after 9 months of androgen suppression and after 3 months off treatment. Cognitive tests measured spatial abilities, spatial memory, verbal fluency, verbal memory and selective attention. A total of 19 patients 52 to 76 years old completed the intermittent androgen suppression study along with 15 healthy community dwelling control participants. RESULTS: Combined androgen blockade reduced PSA and testosterone in all patients compared to baseline. Patients did not significantly change on measures of verbal and spatial memory, executive functions or language. Patients declined on a measure of spatial rotation and improved on a measure of verbal memory during treatment which continued during the off treatment period. CONCLUSIONS: Although preliminary, these findings demonstrate that 9 months of combined androgen blockade resulted in a beneficial effect on verbal memory but adversely affected a measure of spatial ability. Intermittent androgen suppression for a period of 9 months in otherwise healthy men with prostate cancer may have beneficial and adverse effects on cognition that are selective.

Route learning performance in Alzheimer disease patients.

OBJECTIVE: To examine performance on an objective measure of route learning in Alzheimer disease (AD) patients. BACKGROUND: Topographic disorientation (TD) is a common problem among AD patients. The underlying cognitive deficits that contribute to TD in AD patients are not well understood. METHOD: This study examined 19 healthy older individuals (controls) and 16 AD patients who were administered a comprehensive neuropsychological battery along with a novel Route Learning Test (RLT). Areas assessed included incidental learning, spatial relations. recall of the walking route, and recognition of landmarks. RESULTS: Despite comparable performance on basic visuospatial ability measures, AD patients performed significantly worse than controls on the RLT and evidenced poor incidental learning for environmental details. A measure of egocentric and allocentric orientation ability was the best predictor of RLT performance in AD patients. Among RLT subtests, AD patients performed best on recognition of landmarks compared with recognition and recall of spatial layout or recognition of incidental items in the environment. CONCLUSIONS: Our findings suggest that poor performance on the RLT in AD patients is characteristic of poor spatial orientation or spatial reasoning. Therefore, episodes of TD in AD patients may occur secondary to poor spatial orientation.

Testosterone supplementation improves spatial and verbal memory in healthy older men.

OBJECTIVE: To determine the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men. BACKGROUND: Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with reductions in muscle mass, osteoporosis, decreased sexual activity, and changes in cognition. METHODS: Twenty-five healthy, community-dwelling volunteers, aged 50 to 80 years, completed a randomized, double-blind, placebo-controlled study. Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo (saline) for 6 weeks. Cognitive evaluations were conducted at baseline, week 3, and week 6 of treatment by use of a battery of neuropsychologic tests. RESULTS: Circulating total testosterone was raised an average of 130% from baseline at week 3 and 116% at week 6 in the treatment group. Because of aromatization of testosterone, estradiol increased an average of 77% at week 3 and 73% at week 6 in the treatment group. Significant improvements in cognition were observed for spatial memory (recall of a walking route), spatial ability (block construction), and verbal memory (recall of a short story) in older men treated with testosterone compared with baseline and the placebo group, although improvements were not evident for all measures. CONCLUSIONS: The results suggest that short-term testosterone administration enhances cognitive function in healthy older men. However, it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels, or both. The potential role of testosterone vs its metabolites on cognition requires further research.

Performance on the Rey-Osterrieth Complex Figure Test in Alzheimer disease and vascular dementia.

BACKGROUND: Alzheimer disease (AD) and vascular dementia (VaD) are the two most common age-associated dementias. Neuropsychologic studies have demonstrated visuoconstructional impairment in AD and in VaD. OBJECTIVE: This study used the Rey-Osterrieth Complex Figure to assess and compare specific aspects of visuoconstructional deficits in patients with AD, patients with VaD, and normal age-matched subjects. METHOD: Thirteen normal controls, 20 patients with AD, and 20 patients with VaD were given a neuropsychologic battery as part of a comprehensive evaluation for dementia. The groups were similar in age and education, and the VaD and AD groups had comparable levels of dementia. Based on their previous research on visual deficits in AD, the authors devised a new scoring system that divided the Rey-Osterrieth Complex Figure into six perceptual categories: right, left, upper, lower, basic gestalt, and inner detail. RESULTS: Patients with AD and patients with VaD had significant deficits in all six Rey-Osterrieth Complex Figure scoring categories compared with normal controls. Patients with AD exhibited a pattern of deficits similar to that of patients with VaD, with one significant exception: The patients with AD had increased left-sided errors or inattention. CONCLUSIONS: These results suggest that left hemispatial inattention contributes to impaired performance on visuoconstructional tasks in AD.

Use of the cognitive estimations test to discriminate frontotemporal dementia from Alzheimer's disease.

This study investigated the cognitive estimations test (CET) in patients with frontotemporal dementia (FTD) and Alzheimer's disease (AD). The CET consists of questions which reflect judgment and reasoning. FTD patients, who have predominant frontotemporal atrophy, may give more extreme estimates on the CET compared toAD patients, who have greater temporoparietal pathology. The CET was administered to 31 FTD and 31 AD patients of comparable dementia severity plus 31 normal elderly controls. Both dementia groups gave significantly more extreme estimates on the CET than did the controls, and, contrary to expectations, AD patients gave more extreme estimates than did FTD patients. Extreme CET scores correlated with poor savings and calculations scores on neuropsychological tests. In conclusion, the CET may be particularly impaired in AD because it reflects impaired memory and numerical ability as well as disturbed judgment and reasoning. The CET may also be helpful in discriminating some patients in moderate stages of AD from those with FTD.

The evolution of alexia and simultanagnosia in posterior cortical atrophy.

Early alexia and higher visual impairments characterize Posterior cortical atrophy (PCA), a progressive dementing syndrome most often caused by Alzheimer disease. Posterior cortical atrophy is rare, and the nature of the visual impairments in PCA are unclear. The authors observed two patients who had an insidiously progressive reading difficulty characterized by letter-by-letter reading and otherwise intact cognitive functions. Over time, these patients developed "ventral simultanagnosia" with preserved detection of multiple stimuli but inability to interpret whole scenes. Subsequently, they progressed to Balint syndrome with "dorsal simultanagnosia," optic ataxia, and oculomotor apraxia. Structural imaging was normal, but functional imaging revealed posterior cortical dysfunction. On a letter reading task, both patients had a word superiority effect, and on a whole word reading task, they could not read most words with missing or crosshatched letters. An inability to assess whole scenes progressed to an inability to detect more than one stimulus in an array. These findings suggest an evolution of PCA with progressive difficulty in visual integration beginning with letters, progressing to whole scenes, and culminating in Balint syndrome. These changes may reflect an extension of the pathophysiology of PCA from the extrastriate visual cortex to its occipitotemporal and occipitoparietal connections.

Differences between Alzheimer's disease and vascular dementia on information processing measures.

This study evaluated information processing differences between 30 vascular dementia (VaD) patients, 30 Alzheimer's disease (AD) patients, and 30 normal elderly (NE) controls. They were administered a complex reaction time test, a continuous performance test (CPT), and a neuropsychological battery. Compared to NE, both dementia groups had significantly slower motor reaction times and made more errors on the CPT. Compared to AD patients, the VaD patients were slower in stimulus categorization time and had increasing omission errors and persistent commission errors throughout the CPT trial, VaD, which usually includes frontal-subcortical circuit injury, can impair mental speed and stimulus response initiation.

Hemispatial neglect on visual search tasks in Alzheimer's disease.

Abnormal visual attention may underlie certain visuospatial difficulties in patients with Alzheimer's disease (AD). These patients have hypometabolism and neuropathology in parietal cortex. Given the role of parietal function for visuospatial attention, patients with AD may have relative hemispatial neglect masked by other cognitive disturbances. Fifteen patients with-to-moderate AD and 15 healthy elderly controls matched for age, sex, and education were compared on four measures of neglect the visual search of a complex picture, a letter cancellation task, the Schenkenberg line bisection test, and a computerized line bisection task. Compared with controls, the group with AD was significantly impaired overall in attending to left hemispace on both picture search (F[1,56] = 11.27, p < 0.05) and cancellation tasks (F[1,112] = 12.68, p < 0.01); however, a subgroup of patients with AD had disproportionate difficulty in attending to right hemispace. The performance of the groups did not differ on either of the line bisection tasks regardless of the hand used. In AD, hemispatial neglect on visual search tasks may relate to difficulty in disengaging attention or in visual exploration, as well as to the severity of the disease. Future investigations may implicate neglect in visually related deficits in AD, for example, the prominent difficulty with left turns on driving a car.

Frontotemporal dementia versus vascular dementia: differential features on mental status examination.

OBJECTIVE: After Alzheimer's disease, vascular dementia (VaD) and frontotemporal dementia (FTD) are among the most common dementing illnesses. FTD may have a neuropsychological profile similar to that of VaD, and patients with these dementias may be difficult to distinguish on clinical examination. The purpose of this study was to elucidate distinct cognitive profiles of a large group of FTD and VaD patients on a brief, clinical mental status examination. DESIGN: A comparison of 39 FTD patients and 39 VaD patients on a brief, clinical mental status examination. SETTING: A Dementia Research Center and affiliated, university hospitals. METHODS: The FTD patients were diagnosed by noncognitive clinical and neuroimaging criteria, and the VaD patients met NINDS-AIREN criteria for vascular dementia. The two dementia groups were comparable on three dementia assessment scales. MEASUREMENTS: The mental status measures included the neuropsychological battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), plus supplementation from the Neurobehavioral Cognitive Status Examination (NCSE) for cognitive areas not assessed by the CERAD). RESULTS: The FTD and VaD groups differed significantly on the mental status examination measures. FTD patients performed significantly better than the VaD patients on digit span and constructions, despite comparable performance by both groups on calculations. Although not statistically significant, the FTD group performed worse than the VaD group on verbal fluency and abstractions. These differences were not explained by group differences in age and education. CONCLUSION: These results suggest that cognitive differences between FTD and VaD groups reflect greater frontal pathology in contrast to relative sparing of posterior cortex and subcortical white matter in FTD. These cognitive differences as measured by a mental status examination may help distinguish between these two dementia syndromes.