Semantic interference deficits and the detection of mild Alzheimer's disease and mild cognitive impairment without dementia.

Impairment in delayed recall has traditionally been considered a hallmark feature of Alzheimer's disease (AD). However, vulnerability to semantic interference may reflect early manifestations of the disorder. In this study, 26 mildly demented AD patients (mild AD), 53 patients with mild cognitive impairment without dementia (MCI), and 53 normal community-dwelling elders were first presented 10 common objects that were recalled over 3 learning trials. Subjects were then presented 10 new semantically related objects followed by recall for the original targets. After controlling for the degree of overall memory impairment, mild AD patients demonstrated greater proactive but equivalent retroactive interference relative to MCI patients. Normal elderly subjects exhibited the least amount of proactive and retroactive interference effects. Recall for targets susceptible to proactive interference correctly classified 81.3% of MCI patients and 81.3% of normal elderly subjects, outperforming measures of delayed recall and rate of forgetting. Adding recognition memory scores to the model enhanced both sensitivity (84.6%) and specificity (88.5%). A combination of proactive and retroactive interference measures yielded sensitivity of 84.6% and specificity of 96.2% in differentiating mild AD patients from normal older adults. Susceptibility to proactive semantic interference may be an early cognitive feature of MCI and AD patients presenting for clinical evaluation.     

Attention and memory in the preclinical stage of dementia

The aim of this study was to investigate whether attention may be specifically impaired in Alzheimer's disease from the early stages of the disease. Subgroups of patients with different types of mild cognitive impairment were selected according to standard criteria. Patients and controls were given tasks exploring various subcomponents of attention and executive functions. Only subgroups of mild cognitive impairment characterized by memory disorders obtained lower scores than controls on attention and executive tasks. On the basis of the scores obtained on the Clinical Dementia Rating at the 1-year follow-up, patients were redistributed into 2 groups: those who developed and those who did not develop dementia. Patients who presented evolution to dementia already had, at baseline, lower scores than patients who did not evolve on tasks exploring attention and executive functions. The results suggest that not only memory disorders but also attention/executive deficits may characterize dementia at the onset.     

Evolution of cognitive deficits and conversion to dementia in patients with mild cognitive impairment: a very-long-term follow-up study

Ten patients with mild cognitive impairment (MCI) underwent extensive neuropsychological evaluation at 12-monthly intervals for a minimum of 6 years. All 10 patients declined and 5 have now died. The onset of dementia, as defined by a fall in global cognitive function (MMSE <24) or activities of daily living (Clinical Dementia Rating Scale; CDR) ranged from 1 to 8 years with generally good concordance between these measures. The rate of decline on the MMSE was highly variable ranging from 0.86 to 2.83 points per year. Other than a consistent impairment on tests of episodic memory and category fluency (8 out of 10), other early cognitive deficits were difficult to define and tended to be unstable in the early stages. Impairment of semantic memory, visuo-spatial and attentional abilities eventually developed but the sequence of deficit acquisition was heterogeneous. These findings are discussed in the light of current views of MCI. Amnestic MCI may not be an accurate concept unless semantic memory impairment is also considered as an integral core deficit. Full-blown dementia may take many years to develop in patients with MCI but was a universal feature in this study.     

An investigation of PreMCI: subtypes and longitudinal outcomes

Background/AimsTo investigate the clinical features and rates of progression of conditions that are not considered to be normal, but do not fulfill criteria for mild cognitive impairment (MCI).MethodsWe longitudinally evaluated 269 elderly subjects who did not meet formal criteria for MCI at baseline but had: (1) a clinical history suggesting MCI without neuropsychological deficits (PreMCI-Clinical); or (2) neuropsychological deficits on one or more memory measures in conjunction with a negative clinical examination (amnestic PreMCI-NP) or were normal on both neuropsychological and clinical examination.ResultsThe rate of progression to MCI or dementia over an average of 2- to 3 years was 3.7% for no cognitive impairment subjects, whereas it was significantly greater for all PreMCI subtypes (22.0% for PreMCI-Clinical, 38.9% for amnestic PreMCI-NP subjects with two or more memory impairments). Among PreMCI subjects as a whole, lower baseline scores on object memory and category fluency tests were the best predictors of progression to MCI or dementia. Cardiovascular risk factors, Parkinsonian symptoms, and hippocampal atrophy were not associated with progression.ConclusionDistinct PreMCI subtypes defined on the basis of clinical and neuropsychological evaluations were found to have distinct characteristics, but both subtypes demonstrated elevated risk for progression to MCI or dementia. Despite the lack of evidence of clinical impairment, subjects with neuropsychological deficits in two memory domains were particularly at increased risk for progression of their deficits.     

Reduced semantic fluency as an additional screening tool for subjects with questionable dementia

BACKGROUND: Subjective memory complaints in subjects with mild cognitive impairment may represent a genuine decline in episodic memory. This paper evaluates the neuropsychological correlates of the semantic fluency test in subjects with questionable dementia (QD). METHODS: A total of 331 Chinese subjects (118 normal controls, NC, 150 with QD and 63 with mild Alzheimer's disease, AD) were assessed with the Category Verbal Fluency Test (CVFT), the AD Assessment Scale-cognitive subscale (ADAS-Cog), and digit and verbal span tests. CVFT performance was evaluated in each Clinical Dementia Rating (CDR) group. The total number of exemplars, the subcategory and the category size generated were evaluated. Neuropsychological correlates of CVFT scores were computed. RESULTS: Significant differences in CVFT performance were found between the different CDR groups. The subjects with QD had intermediate scores compared to the NC and AD subjects (1-way ANOVA, p < 0.001, post-hoc Bonferroni comparisons). In NC the CVFT scores were significantly associated with ADAS-Cog total, and immediate and delayed recall scores (partial correlations controlled for age and education, p < 0.005). In the QD group the CVFT scores were correlated with ADAS-Cog total, and immediate recall and object naming scores (partial correlation controlled for age and education, p < 0.005). Regression analysis revealed that age and delayed recall were significant predictors of CVFT performance in NCs. In the QD group, age, ADAS-Cog immediate recall and object naming scores predicted the CVFT performance. CONCLUSIONS: The CVFT was impaired in the subjects with QD. Apart from episodic memory, semantic memory deficits also occur early in AD. The different cognitive predictors of CVFT scores in the NC and QD groups suggest that the test is associated with specific psychological functions at different stages of cognitive impairment.     

Natural history of mild cognitive impairment in older persons

BACKGROUND: Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment. METHODS: Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education. RESULTS: On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34%) persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment. CONCLUSIONS: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.     

Episodic and Semantic Memory: A Comparison of Amnesic and Demented Patients

Abstract

Episodic (recall of passages) and semantic (letter and category fluency) memory tasks were administered to Alzheimer's Disease (early stages), Huntington's Disease (HD), and alcoholic Korsakoff patients matched for overall severity of dementia. Although all three patient groups were severely (and equally) impaired on memory for passages, only the Alzheimer and Korsakoff patients emitted numerous intrusion errors. On the fluency tasks, the performance of the mild Alzheimer patients was distinguishable from that of the other two patient groups. On both fluency tasks, the HD and Korsakoff patients demonstrated severe and moderate deficits, respectively, whereas the mild Alzheimer patients were impaired only on the category fluency task. As with the episodic memory test, the Alzheimer and Korsakoff patients made more perseverative errors than did the HD patients on letter fluency. These findings suggest that Alzheimer and HD patients' impairments on episodic and semantic memory tasks reflect different underlying processes. The performance of Alzheimer patients is affected by their language dysfunction and an increased sensitivity to proactive interference; the deficits of the HD patients appear due to a general retrieval problem. Similarities in the error patterns (i.e., perseveration errors) of Alzheimer and Korsakoff patients are discussed with regard to recent neuropathological findings.     

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。     

The underlying mechanisms of verbal fluency deficit in frontotemporal dementia and semantic dementia

Verbal fluency tasks are commonly used to explore semantic memory and executive functions. The aim of this study was to gain a better understanding of the cognitive and neural mechanisms underlying verbal fluency impairment in the frontal variant of frontotemporal dementia (fv-FTD) and in semantic dementia (SD). Semantic and phonemic fluency tasks were performed by 36 fv-FTD and SD patients and 18 elderly controls. We also carried out a neuropsychological investigation of semantic memory, working memory and shifting and updating processes. We performed correlative and regression analyses of fluency scores and neuropsychological data. In addition, patients underwent a resting positron emission tomography examination, and statistical parametric mapping was used to establish correlations between resting-state FDG uptake in the whole brain and fluency scores for each patient group. Both patient groups displayed impaired performances on both fluency tasks compared with controls, but with different patterns. While fv-FTD patients scored higher than SD patients on semantic fluency, their performances on the phonemic task did not differ. Correlation and regression analyses clearly demonstrated that the fv-FTD patients’ performances on both fluency tasks depended on their executive abilities, while those of the SD patients were hampered by the impairment of their semantic memory store. Correlations with resting FDG uptake were consistent with the results of the cognitive study. In fv-FTD, both fluency performances were related to the metabolism of the frontal lobes, while we observed significant correlations between performances on both fluency tasks and the left temporal lobe metabolism in SD.     

Mild cognitive impairment: deficits in cognitive domains other than memory

Patients with mild cognitive impairment (MCI) typically present with memory complaints, but may have mild deficits in other cognitive domains. We compared the neuropsychological profiles of a series of consecutive MCI patients (n = 116) with a control group of healthy elderly subjects (n = 63). The presence of a memory deficit on delayed recall was consistent in the MCI sample, as it was an inclusion criterion in the study. Impairment on immediate recall was present in 62.6% of the patients on paragraph recall of the logical memory test and in 63.1% of the patients on the word paired-associate learning test. Remarkably, patients with MCI frequently had deficits in cognitive domains beyond memory. As much as 68.7% of the patients had deficits in temporal orientation, 30.2% had deficits in semantic fluency, 33.7% in the Token test, 23.4% in calculation, and 23.9% in motor initiative. If detailed neuropsychological testing is performed, the majority of MCI patients will have deficits in cognitive domains other than memory.     

Multiple cognitive deficits in amnestic mild cognitive impairment

OBJECTIVE: To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI). METHODS: From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease (AD) patients on a battery of neuropsychological tests. RESULT: In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group (vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks. CONCLUSIONS: Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI.     

Nonepisodic memory deficits in amnestic MCI.

OBJECTIVE: To (a) compare patients with amnestic Mild Cognitive Impairment (MCI), mild Alzheimer disease (AD), and a group of healthy elderly persons on nonepisodic memory measures; (b) examine which measures are independent of level of education in the groups studied. BACKGROUND: Episodic memory impairment is a cardinal feature of preclinical AD. However, a number of other cognitive measures are also sensitive to the preclinical stage of AD and deficits in multiple domains characterize AD several years before clinical diagnosis. MATERIALS AND METHODS: Patients with amnestic MCI (N=31), patients with mild probable AD (N=15), and healthy elderly controls (N=27) were compared on nonepisodic memory tasks measuring fluid intelligence, working memory, processing speed, verbal fluency, and visual-perceptual and motor functions. Amnestic MCI patients were selected based on clinical criteria and a subgroup was also selected based on psychometric criteria. RESULTS: Multivariate analyses of covariance, controlling for the effects of age, education, and sex, showed that fluid intelligence, working memory, processing speed, semantic fluency, visual-perceptual function, and complex motor function were significantly worse in the MCI than the elderly control group. Working memory, processing speed, semantic fluency, and complex motor tasks were significantly worse in the mild probable AD than the MCI group. The analyses were corroborated using the psychometrically derived MCI group. CONCLUSIONS: (a) Performance on multiple nonepisodic memory measures is affected in the preclinical stage of AD, indicating that broad cognitive impairment characterizes that stage. (b) Complex motor tasks were independent of level of education in our sample, and may have practical utility in the early detection of dementia.     

Psychometric analysis of the selective reminding procedure in a sample from the general elderly population

The selective reminding procedure (SRP) has been proposed for the assessment of distinct aspects of episodic memory, i.e. storage to and retrieval from short-term and long-term memory, item learning and list learning, and as dementia screening tool. In the present study SRP results were analysed in 256 probands from the general elderly population. SRP scores were highly intercorrelated, and principal component analysis yielded only one single factor. The SRP scores were moderately and not differentially correlated with immediate and delayed free recall and recognition and with verbal fluency. All SRP scores discriminated nondemented probands with episodic long-term memory impairment from those without. The MMSE performed significantly better than any SRP score in detecting dementia. The theory-based assumption that the SRP allows assessment of different, independent aspects of memory could not be validated. It is suggested that the SRP is a mixed measure of semantic memory, episodic long-term and short-term memory, and working memory, and that the different SRP scores do not allow to assess different memory functions. Thus, the SRP may neither be recommended for assessment of different subfunctions of memory nor for dementia screening.     

Verbal fluency patterns in amnestic mild cognitive impairment are characteristic of Alzheimer's type dementia.

Amnestic mild cognitive impairment (aMCI) represents a high-risk factor for Alzheimer's disease (AD) and is characterized by a selective decline in episodic memory. Although by definition aMCI is not associated with impaired verbal fluency performance, we examined relative differences between fluency tasks because AD is characterized by poorer semantic than phonemic fluency. Phonemic and semantic fluency trials were administered to 46 healthy controls, 33 patients with aMCI, and 33 patients with AD. Results revealed a progressive advantage (controls > aMCI > AD) in semantic, relative to phonemic fluency. Difference scores between tasks distinguished each group from the others with medium to large effect sizes (d) ranging from 0.49 to 1.07. Semantic fluency relies more on semantic associations between category exemplars than does phonemic fluency. This aMCI fluency pattern reflects degradation of semantic networks demonstrating that initial neuropathology may extend beyond known early changes in hippocampal regions.     

Alternate forms of logical memory and verbal fluency tasks for repeated testing in early cognitive changes

BACKGROUND: Repeat cognitive testing is an essential diagnostic strategy to measure changes in cognition over time when following people with memory problems. Alternate forms may avert practice effects that can mimic improvements in cognition. We evaluated alternate forms of verbal fluency and logical memory (paragraph recall) tasks to evaluate their equivalence for clinical use. METHODS: Participants with mild cognitive impairment (MCI) and dementia were recruited from five outpatient memory clinics and one nursing home. Participants with normal cognition (NC) were recruited from family members or friends. Verbal fluency categories of animals, cities & towns, fruits & vegetables and first names were used. Scores were recorded for 0-30 seconds, 31-60 seconds and errors. For the logical memory task, participants were read one of three different paragraphs and then were asked to recall the story. Immediate recall and delayed recall scores were recorded. The Standardized Mini-mental State Examination, the AB Cognitive Screen and the 15-point Geriatric Depression Scale were administered as part of the assessment. Analyses were performed using means, frequency distributions, t-tests, receiver-operating characteristic curves and effect sizes. RESULTS: There were 46 NC participants, 45 with MCI and 55 with dementia. For verbal fluency, the mean number of animals, cities & towns, names or fruits & vegetables named in 60 seconds did not differ significantly within each cognitive group. First names was an easier category than the others: NC named 16.9-22.3 items, MCI named 11.6-14.4 items and dementia named 8.1-11.4 items. The mean number of items immediately recalled in logical memory was not significantly different for the three paragraphs. The verbal fluency task (in 60 seconds) and logical memory immediate recall were highly sensitive and specific to differences between NC and MCI (areas under the curves 0.87 and 0.76, respectively). CONCLUSIONS: Alternate forms allow serial testing without learning bias. Verbal fluency and logical memory tasks are sensitive to early cognitive changes.     

Synaptic loss in the inferior temporal gyrus in mild cognitive impairment and Alzheimer's disease

Alzheimer's disease (AD) is a slowly progressing form of dementia characterized in its earliest stages as a loss of memory. Individuals with amnestic mild cognitive impairment (aMCI) may be in the earliest stages of the disease and represent an opportunity to identify pathological changes related to the progression of AD. Synaptic loss is one of the hallmarks of AD and associated with cognitive impairment. The inferior temporal gyrus plays an important role in verbal fluency, a cognitive function affected early in the onset of AD. Unbiased stereology coupled with electron microscopy was used to quantify total synaptic numbers in lamina 3 of the inferior temporal gyrus from short postmortem autopsy tissue harvested from subjects who died at different cognitive stages during the progression of AD. Individuals with aMCI had significantly fewer synapses (36%) compared to individuals with no cognitive impairment. Individuals with AD showed a loss of synapses very similar to the aMCI cohort. Synaptic numbers correlated highly with Mini Mental State Examination scores and a test of category verbal fluency. These results demonstrate that the inferior temporal gyrus is affected during the prodromal stage of the disease and may underlie some of the early AD-related clinical dysfunctions.     

Similar patterns of cognitive deficits in the preclinical phases of vascular dementia and Alzheimer's disease.

We investigated whether (1) cognitive deficits are present among persons who will be diagnosed with vascular dementia (VaD) 3 years later, and (2) the pattern of such deficits is similar to that observed in preclinical Alzheimer's disease (AD). The VaD diagnosis was a diagnosis of post-stroke dementia. Population-based samples of 15 incident VaD cases, 43 incident AD cases, and 149 normal controls were compared on tests of episodic and short-term memory, verbal fluency, and visuospatial skill. Both dementia groups showed preclinical impairment relative controls on tasks assessing episodic memory 3 years before diagnosis, and there were no differences between these groups on any cognitive measure. The existence of a preclinical phase in the present VaD cases suggests that circulatory disturbance may affect cognitive performance before the occurrence of stroke that leads to clinical VaD. These results extend previous findings of similar patterns of cognitive deficits in the early clinical phases of AD and VaD to the preclinical phases of these diseases.     

Fonctions cognitives sous-jacentes aux déficits de fluence verbale dans la schizophrénie : revue de la littérature

Individuals with schizophrenia usually show impairment on various cognitive functions, including long-term memory, executive functions and language. Compared to healthy controls, their performance is impaired in verbal fluency tests. These tests require participants to generate in a given time as many words as they can, belonging to a given category (semantic fluency), or beginning with a specific letter (orthographic fluency). Various cognitive functions are involved in verbal fluency tests: psychomotor speed, executive functions, language, long-term verbal memory and semantic memory. The purpose of the present study was to clarify the functional origin of verbal fluency deficits in schizophrenia through a literature review. Nineteen articles were selected in Pubmed and PsycINFO after initial screening and detailed review. They were formally analyzed with regard to general performance, cognitive strategies used in semantic and orthographic fluency tests and, underlying cognitive origin of deficits. Results show that individuals with schizophrenia produce fewer words than healthy controls in both types of fluency tests. Their impairment is more apparent in semantic than in orthographic fluency tests. Results of studies reviewed also show that individuals with schizophrenia adopt the same clustering (i.e. production of related words within a subcategory) and switching (i.e. ability to shift between clusters when a subcategory is exhausted) strategies than healthy controls, but less efficiently. Several hypotheses, such as the impairment of executive functions, semantic memory or speed of information processing, were put forward to account for this finding. Interestingly, the few studies in which researchers performed an analysis of the semantic relationships between words produced in fluency tests showed a less semantic coherence among people with schizophrenia than in healthy controls. Such a difference could be explained by disorganization of semantic memory or impairment in the activation of conceptual representations in semantic memory. Studies in which correlations and regression analyzes were performed allow for clarifying the cognitive origin underlying verbal fluency deficits in schizophrenia. The links between these deficits and information processing speed as well as working memory are well established. These two cognitive domains also appear to be strong predictors of performance in semantic and orthographic fluency tasks in schizophrenia. Individuals with schizophrenia usually present with a significant slowdown in the speed of information processing. Such a slowdown is likely to account for their poor performance in verbal fluency tests, which require the independent and rapid production of words. Working memory disorders are also core cognitive symptoms of schizophrenia. Working memory is involved in verbal fluency tests since they involve “strategic” activation of verbal information in long-term memory, inhibition of inappropriate words, switching between clusters, etc. However, the concept of working memory also partially encompasses the notion of executive functions so that the results reported in the present literature review, according to which impairment of verbal fluency in schizophrenia results from working memory deficits but not from executive functions deficits, are difficult to interpret. Results are also less clear-cut in regard to verbal long-term memory and to language abilities. Finally, numerous studies had shown that individuals with schizophrenia present specific deficits in the organization of semantic memory. However, the impact of this deficit on verbal fluency was explored in one study only. To conclude, verbal fluency tests are sensitive to various neurocognitive conditions and are helpful for differential diagnosis. Further studies are still needed to clarify the functional origin of verbal fluency deficits in schizophrenia, in particular the differential role of executive functions and working memory as well as the impact of semantic memory impairment.     

Letter and semantic fluency in older adults: effects of mild depressive symptoms and age-stratified normative data

Depression induced cognitive impairment, also referred to as the dementia syndrome of depression or pseudodementia, has been well characterized, yet the extent to which the more common mild depressive symptoms influence cognition has not been well studied. We sought to identify the influence of mild depressive symptoms on verbal fluency performance in a large sample of healthy community dwelling older adults. Letter and semantic fluency testing was conducted on 188 participants (ages 60-92 years) with no known history of neurologic or psychiatric disease. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS). A total of 39 subjects obtained GDS scores consistent with mild depressive symptoms (GDS=10-19), and 149 subjects were identified as not depressed (GDS<10). ANOVA indicated that subjects with mild depressive symptoms performed significantly worse than normal controls on letter fluency (p<.05), but there was no significant difference between the groups on semantic fluency. Analysis of the nondepressed group stratified into young-old, middle-old, and oldest-old revealed a significant decline in semantic (p<.001) but not letter fluency with age. The nondepressed young-old showed the expected advantage for word list generation to semantic as compared to letter categories, yet this pattern was reversed in the older age groups, where letter fluency scores exceeded semantic fluency scores. Our results suggest that the presence of even mild depressive symptoms may confound using letter versus category discrepancies in the differential diagnosis of dementia. Further, our findings suggest that the commonly used strategy of examining letter-semantic fluency discrepancies may not be relevant for individuals of advanced age. Age-stratified normative data for fluency testing in older adults is also provided.