Neuropsychological differentiation of dementia with Lewy bodies from normal aging and Alzheimer's disease

We examined the diagnostic utility of selected neuropsychological measures in the differentiation of dementia with Lewy bodies (DLB) from normal aging and Alzheimer's disease (AD). Patients with DLB (n = 87), AD (n = 138), and a group of normal controls (n = 103) were recruited from the Mayo Alzheimer's disease patient registry and Alzheimer's Disease Research Center. Neuropsychological measures shown to have utility in previous studies were included in the analysis. The final multivariate logistic regression model distinguishing DLB from normal controls included Auditory Verbal Learning Test (AVLT) percent retention, Block Design, Trail Making Test-Part A, and Benton Visual Form Discrimination. This model has a sensitivity of 88.6% and specificity of 96.1%. The final multivariate logistic model distinguishing DLB from AD included Trail Making Part A, Boston Naming Test (BNT), AVLT percent retention, and copy of the Rey-Osterrieth Complex Figure. This model had a sensitivity of 83.3% and a specificity of 91.4%. AVLT and BNT had negative coefficients, indicating that lower scores decreased the likelihood of DLB relative to AD. These finding extend prior research suggesting a cognitive profile that can aid in the clinical diagnosis of DLB. Early attention and visual perceptual disturbance suggests DLB, while early impairment in memory and naming suggests AD.     

Utility of behavioral versus cognitive measures in differentiating between subtypes of frontotemporal lobar degeneration and Alzheimer's disease

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer's disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of 'executive functioning'). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.     

Neuropsychological Differentiation of Dementia with Lewy Bodies from Normal Aging and Alzheimer's Disease

We examined the diagnostic utility of selected neuropsychological measures in the differentiation of dementia with Lewy bodies (DLB) from normal aging and Alzheimer's disease (AD). Patients with DLB (n = 87), AD (n = 138), and a group of normal controls (n = 103) were recruited from the Mayo Alzheimer's disease patient registry and Alzheimer's Disease Research Center. Neuropsychological measures shown to have utility in previous studies were included in the analysis. The final multivariate logistic regression model distinguishing DLB from normal controls included Auditory Verbal Learning Test (AVLT) percent retention, Block Design, Trail Making Test—Part A, and Benton Visual Form Discrimination. This model has a sensitivity of 88.6% and specificity of 96.1%. The final multivariate logistic model distinguishing DLB from AD included Trail Making Part A, Boston Naming Test (BNT), AVLT percent retention, and copy of the Rey-Osterrieth Complex Figure. This model had a sensitivity of 83.3% and a specificity of 91.4%. AVLT and BNT had negative coefficients, indicating that lower scores decreased the likelihood of DLB relative to AD. These finding extend prior research suggesting a cognitive profile that can aid in the clinical diagnosis of DLB. Early attention and visual perceptual disturbance suggests DLB, while early impairment in memory and naming suggests AD.     

Alzheimer's disease can be accurately diagnosed in very mildly impaired individuals

BACKGROUND: The growing propensity to diagnose AD in individuals with very mild cognitive impairment increases the danger of false-positive diagnostic errors. Unfortunately, there is little systematically acquired information about the accuracy of the AD diagnosis in very mildly impaired patients. OBJECTIVE: To determine the accuracy of the diagnosis of AD in very mildly impaired patients and to identify objective measures that effectively distinguish these patients from elderly normal controls (NC). METHODS: Consecutive patients with Mini-Mental State Examination scores of > or = 24 who received a clinical diagnosis of AD were evaluated annually for at least 3 years. The initial diagnosis was verified or refuted by autopsy or by information obtained in subsequent evaluations. Initial neuropsychological test scores of verified AD patients were compared with those of NC subjects to identify effective diagnostic measures. RESULTS: The diagnosis of AD was confirmed in 98 of 110 (89%) very mildly impaired patients (33/36 by autopsy, 65/74 by disease progression). The diagnosis was inaccurate in 12 patients (11%): Seven were subsequently diagnosed with other neurologic disorders, and five were ultimately found to be normal. Neuropsychological measures of delayed recall, verbal fluency, and global cognitive status (i.e., Mattis Dementia Rating Scale) provided excellent sensitivity (> or = 96%) and specificity (> or = 93%) for differentiating between very mildly impaired AD patients and NC subjects. CONCLUSIONS: When comprehensive assessment procedures are employed, AD can be diagnosed with reasonably high accuracy in very mildly impaired individuals. However, the dementia evaluation should be repeated after approximately 1 year to ensure the accuracy of the initial diagnosis.     

Prediction of all-cause dementia using neuropsychological tests within 10 and 5 years of diagnosis in a community-based sample

While neuropsychological tests have been identified for the early prediction of Alzheimer's disease, this has not been established for prediction of all-cause dementia. This would be helpful for clinicians concerned about the risk of progression to dementia in patients who may present with a variety of medical and neurological conditions. We wanted to determine whether neuropsychological tests could accurately predict incident dementia within 10 and five years of diagnosis in a community-based sample. The Canadian Study of Health and Aging was conducted in three waves over a 10-year period (1991-2002). We studied 1472 non-demented participants who completed neuropsychological testing in 1991 and received a diagnostic assessment for dementia in 2001 (n = 284). We also studied 1231 non-demented participants who completed neuropsychological testing in 1996 and received a diagnostic assessment in 2001 (n = 634). Diagnosticians were blinded to performance on the predictive tests. Age, education, and sex were included as covariates in all regression analysis. Ten-year prediction: 2 tests, Rey Auditory Verbal Learning Test (RAVLT) short delayed verbal recall and Wechsler Adult Intelligence Test Revised (WAIS-R) Digit Symbol, were significant predictors of dementia (sensitivity = 78%, specificity = 72%, positive likelihood ratio = 2.81). Five-year prediction: 4 tests, Wechsler Memory Scale Information, RAVLT short delayed verbal recall, animal fluency, and WAIS-R Digit Symbol, significantly predicted incident dementia (sensitivity = 75%, specificity = 74%, positive likelihood ratio = 2.90). Regression models were supported with bootstrapping estimates. Neuropsychological tests can accurately predict progression to all-cause dementia within 10 years of diagnosis in a large community-based sample of non-demented participants.     

Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment

BACKGROUND: In cognitively impaired patients without dementia, the utility of apolipoprotein E (APOE) genotyping is unclear. OBJECTIVE: To evaluate the predictive utility of the APOE epsilon4 genotype for conversion to probable Alzheimer disease (AD). DESIGN: Naturalistic, longitudinal study. SETTING: Memory disorders outpatient clinic. PATIENTS: A total of 136 patients with memory complaints were determined to have mild cognitive impairment and were evaluated every 6 months. Fifty-seven age- and sex-matched healthy controls were evaluated annually. MAIN OUTCOME MEASURES: Primary outcome measures included conversion to AD. Secondary outcome measures included change over time in Mini-Mental State Examination (MMSE) score and Selective Reminding Test (SRT) delayed recall score. RESULTS: The APOE epsilon4 allele was present in 25% of patients and 21% of healthy controls. During a mean +/- SD follow-up of 35.2 +/- 24.3 months, 35 of 136 patients converted to AD. APOE epsilon4 carrier status did not differ between converters (31%) and nonconverters to AD (23%, P = .3) and did not affect the time trend in MMSE or SRT scores in the entire sample. Four of 5 APOE epsilon4 homozygotes converted to AD compared with 7 of 29 heterozygotes (P = .02). In a Cox proportional hazards model stratified by age quartiles, after controlling for sex, education, MMSE score, and SRT delayed recall score, APOE epsilon4 increased the risk of AD in patients 70 to 85 years old (n = 57; risk ratio, 2.77; 95% confidence interval, 1.1-7.3; P = .03) but not in patients 55 to 69 years old (n = 79; P = .7). CONCLUSIONS: APOE epsilon4 carrier status was associated with conversion to AD in older outpatients after controlling for known demographic and clinical risk factors, and APOE epsilon4 homozygosity was associated with increased risk of conversion to AD. However, APOE epsilon4 carrier status by itself did not predict cognitive decline or conversion to AD, indicating that APOE genotyping in patients with mild cognitive impairment may have limited clinical applicability for prediction of outcome.     

APOE genotype,memory test performance,and the risk of Alzheimer's disease in the Canadian Study of Health and Aging

OBJECTIVES: This study examined the relation between two risks for Alzheimer's disease (AD): the apolipoprotein (APOE) epsilon4 allele and poor memory test performance. METHODS: In the Canadian Study of Health and Aging (CSHA), a 5-year longitudinal population-based study that screened and followed over 10,000 participants, 2,914 had an initial clinical assessment and 1,624 had APOE genotype testing. All participants were categorized as having no cognitive impairment, cognitive impairment but no dementia, or dementia at both baseline and follow-up. We examined those (n = 209) with a complete neuropsychological assessment at baseline and no evidence of cognitive impairment who had either APOE epsilon3/epsilon3 or epsilon3/epsilon4 genotypes and who had a clinical consensus diagnosis of either no cognitive impairment or AD at follow-up. Delayed free recall memory was evaluated at CSHA-1 with the Buschke Cued Recall Test (BCRT). RESULTS: The risk of AD at follow-up was increased for participants with an APOE epsilon3/epsilon4 genotype when memory test performance was not considered, but logistic regression demonstrated that a model which also considered baseline memory test performance was more predictive of AD. In the more complete model, reduced BCRT free recall scores were associated with an increased risk of AD, whereas the risk associated with the APOE epsilon3/epsilon4 genotype was no longer significant. CONCLUSIONS: For those with no evidence of cognitive impairment, drawn from a population-based sample of elderly persons, the APOE epsilon3/epsilon4 genotype was only associated with an increased risk of AD after 5 years if their memory test performance was relatively poor at baseline. Regardless of the APOE genotype, and in the absence of clinical evidence of cognitive impairment, reduced scores on a test of delayed free recall at baseline was associated with an increased risk of AD after 5 years.     

Detecting dementia: novel neuropsychological markers of preclinical Alzheimer's disease

The results of a previous study have suggested that impaired performance on one neuropsychological test, CANTAB Paired Associates Learning (PAL), may serve as a marker for preclinical Alzheimer's disease (AD). In a group of individuals with 'questionable dementia', the baseline PAL performance was found to correlate significantly with subsequent deterioration in global cognitive function over an 8-month period. The present paper reports diagnostic outcome data for the same individuals 32 months after the first assessment and evaluates the predictive diagnostic utility of baseline neuropsychological measures. Thirty-two months after joining the study, 11 of the 43 'questionable dementia' patients met the criteria for probable AD diagnosis ('converters') and 29 remained free from AD ('non-converters'). Logistic regression analysis revealed that two tests of memory, in combination, could be used to predict a later diagnosis of probable AD with a high level of accuracy [chi(2)(3) = 47.054, p < 0.0001]. As predicted, these tests are measures of visuospatial learning (CANTAB PAL) and, also, semantic memory (Graded Naming Test). These two tests in combination appear to be highly accurate in detecting cognitive dysfunction characteristic of preclinical AD. Using these tests, a simple algorithm is described for calculating, with 100% accuracy for this sample of 40 patients, the probability that an individual with mild memory impairments will go on to receive a diagnosis of probable AD.     

Neuropsychological markers of mild cognitive impairment: A clinic based study from urban India

Background:

Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia. Persons with MCI are at higher risk to develop dementia. Identifying MCI from normal aging has become a priority area of research. Neuropsychological assessment could help to identify these high risk individuals.

Objective:

To examine clinical utility and diagnostic accuracy of neuropsychological measures in identifying MCI.

Materials and Methods:

This is a cross-sectional study of 42 participants (22 patients with MCI and 20 normal controls [NC]) between the age of 60 and 80 years. All participants were screened for dementia and later a detailed neuropsychological assessment was carried out.

Results:

Persons with MCI performed significantly poorer than NC on word list (immediate and delayed recall), story recall test, stick construction delayed recall, fluency and Go/No-Go test. Measures of episodic memory especially word list delayed recall had the highest discriminating power compared with measures of semantic memory and executive functioning.

Conclusion:

Word list learning with delayed recall component is a possible candidate for detecting MCI from normal aging.     

Everyday action impairment in Parkinson's disease dementia

This study examined everyday action impairment in participants with Parkinson's disease dementia (PDD) by comparison with participants with Parkinson's disease-no dementia (PD) or Alzheimer's disease (AD) and in reference to a neuropsychological model. Participants with PDD (n = 20), PD (n = 20), or AD (n = 20) were administered performance-based measures of everyday functioning that allowed for the quantification of overall performance and error types. Also, caregiver ratings of functional independence were obtained. On performance-based tests, the PDD group exhibited greater functional impairment than the PD group but comparable overall impairment relative to the AD group. Error patterns did not differ between PDD and PD participants but the PDD group demonstrated a higher proportion of commission errors and lower proportion of omission errors relative to the AD group. Hierarchical regression analyses showed omission errors were significantly predicted by neuropsychological measures of episodic memory, whereas commission errors were predicted by both measures of general dementia severity (MMSE) and executive control. Everyday action impairment in PDD differs quantitatively from PD but qualitatively from AD and may be characterized by a relatively high proportion of commission errors-an error type associated with executive control deficits. (JINS, 2012, 18, 1-12).     

Utility of a modified Mini-Mental State Examination with extended delayed recall in screening for mild cognitive impairment and dementia among community dwelling elders

The objective of this study was to test the utility of additional delayed recall of the three recall items of the Folstein Mini Mental State Evaluation (MMSE) as a screening measure for mild cognitive impairment and dementia in the elderly. It used a cross-sectional study of subjects, who were administered a brief memory screening battery which included the MMSE and extended delayed recall of the three MMSE recall items at 5 minute intervals. The criteria for cognitive status was determined on the basis of the neurological and neuropsychological evaluation. One hundred and two elderly persons who were recruited through a memory screening program were diagnosed as cognitively normal (N=52), mild cognitively impaired (N=24), or demented (N=26). The observed sensitivity of 83.3% and specificity of 90.4% was achieved across three delayed recall trials in differentiating cases with mild cognitive impairment (without dementia) from individuals with normal cognition and was superior to the total MMSE score alone (sensitivity/specificity: 70.8%/84.6%). Cumulative recall for the three MMSE items across only two delayed recall trials demonstrated a sensitivity of 96.2% and specificity of 90.4% in differentiating between cases of dementia versus cases diagnosed with no cognitive impairment. The three trial delayed recall score enhanced prediction of mild cognitive impairment in at-risk elderly living with the community and may have promise in the development of future screening batteries.     

Perception, attention, and working memory are disproportionately impaired in dementia with Lewy bodies compared with Alzheimer's disease

OBJECTIVE: To test the hypotheses that visuoperceptual and attentional ability are disproportionately impaired in patients having dementia with Lewy Bodies (DLB) compared with Alzheimer's disease (AD). METHODS: A comprehensive battery of neuropsychological tasks designed to assess working, episodic, and semantic memory, and visuoperceptual and attentional functions was given to groups of patients with DLB (n=10) and AD (n=9), matched for age, education, and mini mental state examination (MMSE), and to normal controls (n=17). RESULTS: Both patient groups performed equally poorly on tests of episodic and semantic memory with the exception of immediate and delayed story recall, which was worse in the AD group. Digit span was by contrast spared in AD. The most striking differences were on tests of visuoperceptual/spatial ability and attention. Whereas patients with AD performed normally on several subtests of the visual object and space perception battery, the DLB group showed substantial impairments. In keeping with previous studies, the AD group showed deficits in selective attention and set shifting, but patients with DLB were more impaired on virtually every test of attention with deficits in sustained, selective, and divided attention. CONCLUSIONS: Patients with DLB have substantially greater impairment of attention, working memory, and visuoperceptual ability than patients with AD matched for overall dementia severity. Semantic memory seems to be equally affected in DLB and AD, unlike episodic memory, which is worse in AD. These findings may have relevance for our understanding of the genesis of visual hallucinations, and the differential diagnosis of AD and DLB.     

Neuropsychological and functional measures of severity in Alzheimer disease, frontotemporal dementia, and semantic dementia

Many studies attempting to compare the clinical features in different dementia syndromes have attempted to control for overall disease severity using neuropsychological or functional measures. However, these measures may not give equivalent estimates of disease severity. We examined a functional measure of severity (Clinical Dementia Rating scale [CDR] scores) in patients with Alzheimer disease (AD, n = 23), frontotemporal dementia (FTD, n = 24), and semantic dementia (SD, n = 25) who were matched for age and Mini-Mental State Examination (a neuropsychological measure of severity). Total CDR scores were significantly worse in the FTD group compared with both AD and SD patients, whose total CDR scores were similar to each other. FTD showed no difference in memory or orientation compared with AD but did show more impairment in judgment and problem solving, community affairs, home and hobbies, and personal care compared with AD and SD. Thus, in FTD the CDR reveals functional impairments in a wide variety of domains that are more severe than those seen in AD or SD patients with an equivalent Mini-Mental State Examination.     

Relation between vascular risk factors and neuropsychological test performance among elderly persons with Alzheimer's disease

BACKGROUND: Vascular risk factors increase the risk of Alzheimer's disease (AD). The mechanisms for these associations are unclear, and may be due to misdiagnosis of a vascular dementia syndrome as AD. OBJECTIVE: To examine differences in neuropsychological profile among persons diagnosed clinically with AD with and without vascular risk factors or stroke. METHODS: Community based cohort study. Individual and composite scores of neuropsychological tests at the time of clinical diagnosis of incident AD were compared among 243 persons with and without vascular risk factors or stroke. RESULTS: Among subjects with incident AD, diabetes was associated with lower performance in Delayed Recall of the Selective Reminding Test (SRT), while persons diagnosed with hypertension scored lower in consistent long term recall (CLTR) of the SRT and current smokers scored lower in Category Fluency. None of the risk factors was associated with differences in composite scores in memory, abstract/visuospatial or language domain, nor was the number of risk factors per person. Persons with stroke had a higher delayed recall score at the time of AD diagnosis. CONCLUSION: The presence of vascular risk factors among persons with clinically diagnosed AD was associated with subtle differences in neuropsychological profile at the time of diagnosis. This study needs to be replicated in samples with brain imaging, a comprehensive executive abilities battery, and pathological diagnosis of AD.     

Boston naming test short forms: a comparison of previous forms with new item response theory based forms

Two new short forms of the Boston Naming Test (BNT) were developed using item response theory (IRT) with data from 206 elderly outpatients. We evaluated the diagnostic ability of 12 short forms among the full sample and in a sub-sample of 69 patients diagnosed with mild Alzheimer's disease (AD) either alone or in combination with vascular dementia (VD). The full BNT (reliability alpha = .90) identified 44% of the AD/VD patients as abnormal on naming. Our 30 item short form (alpha = .90) also identified 44% of the AD/VD patients as abnormal, with 93% agreement with the full BNT on abnormal AD/VD patient classifications. Our 15 item short form (alpha = .84) identified 48% of the AD/VD patients as abnormal, with 90% agreement with the full BNT's abnormal classifications. An adaptive 30/15 item version equaled the performance of the full 30 item test while requiring only 15 items for 75% of the patients with normal naming ability. This study illustrates the utility of IRT for developing neuropsychological assessment tools.     

Preclinical dementia: an Italian multicentre study on amnestic mild cognitive impairment

BACKGROUND: Different rates and cognitive predictors of conversion to dementia have been reported in subjects with different kinds of mild cognitive impairment (MCI). METHODS: A prospective, 24-month follow-up study, involving 269 subjects who strictly fulfilled criteria for the amnestic MCI. RESULTS: Conversion rate to dementia was 21.4% per year. Seventy-nine out of the 83 individuals who developed dementia were affected by probable Alzheimer's disease (AD). Among others, at the 24-month follow-up 24.1% were still affected by amnestic MCI, 13.3% had changed their neuropsychological profile of impairment and 17.2% were cognitively normalised. Compared to subjects who did not convert to AD, those who did convert showed poorer immediate and delayed recall and recognition of verbal and visual material at baseline as well as reduced executive abilities. A combination of age, Clinical Dementia Rating boxes and scores on delayed recall and recognition of verbal and visual material accurately identified 86% of the subjects who developed AD. CONCLUSIONS: Elderly subjects affected by an isolated memory disorder have a high probability of developing AD. The ability of verbal and visual measures to predict incipient dementia of memory impairment may be increased by the simultaneous assessment of individual features, such as age or rate of functional impairment.     

抑郁症和早期阿尔茨海默病的记忆和执行功能

目的 研究抑郁症和早期阿尔茨海默病(AD)的神经心理学特征,试图运用神经心理学评估对两者进行鉴别。方法 对32例单相抑郁症、38例早期AD和34例对照进行WHO-UCLA词语学习、词语流畅、复杂图形和逻辑记忆的评估。结果 早期AD组神经心理学测验得分最低,抑郁症组次之,对照组最高,3组之间有显著性差异(P<0.01);抑郁症组仅表现为词语学习和逻辑记忆的自由回忆以及语义流畅的损害(P<0.05),而早期AD组表现为全面的认知功能损害(P<0.01);逐步判别分析提示,复杂图形延迟自由回忆、词语学习长时延迟自由回忆和语义流畅是区分抑郁症组和早期AD组的重要指标。结论 抑郁症和早期AD认知功能损害的特征不同,长时延迟自由回忆、再认和语义流畅能够区分早期AD和抑郁症。     

Novel applications of social-personality measures to the study of dementia

Despite the realization that personality change is a core feature of frontotemporal dementia (FTD), little work has been performed using personality as a diagnostic tool for this disease. Likewise, personality change in Alzheimer's disease (AD) has long been recognized, but generally has not been used for diagnostic purposes. We introduce novel social-personality measures (Big Five Inventory, Interpersonal Adjectives Scale and Interpersonal Measure of Psychopathy) in the differential diagnosis of AD and temporal subtypes of FTD, and integrate these measures with traditional behavioural and neuropsychological methods commonly used in diagnosing dementia. We present four cases: an FTD patient with predominantly left temporal degeneration, an FTD patient with predominantly right temporal degeneration and two patients with Alzheimer's disease (one with mild and the other with moderate impairment). Results show the diagnostic utility of these measures in differentiating among temporal subtypes of FTD and moderate AD. Right temporal FTD, in particular, shows profound shifts in personality and interpersonal behaviour, as well as a striking lack of insight into these shifts. In addition to diagnostic purposes, we discuss how measures of personality and interpersonal behaviour can be utilized as an important component of understanding disease susceptibility and risk, as well as offering insights into the neuroanatomical underpinnings of personality and social behaviour.     

Memory and executive function impairment predict dementia in Parkinson's disease.

We analyzed the association of neuropsychological test impairment at baseline with the development of dementia in idiopathic Parkinson's disease (PD) patients. A cohort of nondemented PD patients from northern Manhattan, NY was followed annually with neurological and neuropsychological evaluations. The neuropsychological battery included tests of verbal and nonverbal memory, orientation, visuospatial ability, language, and abstract reasoning. The association of baseline neuropsychological tests scores with incident dementia was analyzed using Cox proportional hazards models. The analysis controlled for age, gender, education, duration of PD, and the total Unified Parkinson's Disease Rating Scale motor score at baseline. Forty-five out of 164 patients (27%) became demented during a mean follow-up of 3.7 +/- 2.3 years. Four neuropsychological test scores were significantly associated with incident dementia in the Cox model: total immediate recall (RR: 0.92, 95% CI: 0.87-0.97, P = 0.001) and delayed recall (RR: 0.73, 95% CI: 0.59-0.91, P = 0.005) of the Selective Reminding Test (SRT), letter fluency (RR: 0.87, 95% CI: 0.77-0.99, P = 0.03), and Identities and Oddities of the Mattis Dementia Rating Scale (RR: 0.85, 95% CI: 0.73-0.98, P = 0.03). When the analysis was performed excluding patients with a clinical dementia rating of 0.5 (questionable dementia) at baseline evaluation, total immediate recall and delayed recall were still predictive of dementia in PD. Our results indicate that impairment in verbal memory and executive function are associated with the development of dementia in patients with PD.