Decline In Verbal Fluency Research Articles

Temporal Trends in the Level and Decline of Cognition and Disability in an Elderly Population: The PAQUID Study.

In line with declining trends in dementia incidence, we compared the cognitive and functional evolution of 2 "generations" of elderly individuals aged 78-88 years, who were included 10 years apart in the French Personnes Agées Quid cohort (n = 612 in 1991-1992 and n = 628 in 2001-2002) and followed-up for 12 years with assessments of cognition and disability. The impact of specific risk factors on this evolution was evaluated. Differences between the generations in baseline levels and decline over time were estimated using a joint model to account for differential attrition. Compared with the first generation, the second generation had higher performances at baseline on 4 cognitive tests (from P < 0.005). Differences in global cognition, verbal fluency, and processing speed, but not in working memory, were mostly explained by improvement in educational level. The second generation also exhibited less cognitive decline in verbal fluency and working memory. Progression of disability was less over the follow-up period for the second generation than for the first. The cognitive state of this elderly population improved, partially due to improvements in educational level.

Standardised Neuropsychological Assessment for the Selection of Patients Undergoing DBS for Parkinson's Disease.

DBS is an increasingly offered advanced treatment for Parkinson's disease (PD). Neuropsychological assessment is considered to be an important part of the screening for selection of candidates for this treatment. However, no standardised screening procedure currently exists. In this study, we examined the use of our standardised neuropsychological assessment for the evaluation of surgical candidates and to identify risk factors for subsequent decline in cognition and mood. A total of 40 patients were assessed before and after DBS. Evaluation of mood and case notes review was also undertaken. Before DBS, patients with PD demonstrated frequent impairments in intellectual functioning, memory, attention, and executive function, as well as high rates of mood disorder. Post-DBS, there was a general decline in verbal fluency only, and in one patient, we documented an immediate and irreversible global cognitive decline, which was associated with older age and more encompassing cognitive deficits at baseline. Case note review revealed that a high proportion of patients developed mood disorder, which was associated with higher levels of depression at baseline and greater reduction in levodopa medication. We conclude that our neuropsychological assessment is suitable for the screening of candidates and can identify baseline risk factors, which requires careful consideration before and after surgery.

Slow gait speed is associated with executive function decline in older people with mild to moderate dementia: A one year longitudinal study

ObjectivesThis study aimed to document change in neuropsychological, physical and functional performance over one year and to investigate the relationship between baseline gait speed and cognitive decline in this period in older people with dementia. MethodsOne hundred and seventy-seven older people with dementia (Mini-Mental State Examination 11–23; Addenbrooke’s Cognitive Examination-Revised <83) residing in the community or low level care facility completed baseline neuropsychological, physical and functional assessments. Of these, 134 participants agreed to reassessment of the above measures one year later. ResultsOverall, many neuropsychological, physical and functional performance measures declined significantly over the one year study period. Baseline gait speed was significantly associated with decline in verbal fluency (B(109)=2.893, p=0.046), specifically phonemic/letter fluency (B(109)=2.812, p=0.004) while controlling for age, education, dementia drug use and baseline cognitive performance. There was also a trend for an association between baseline gait speed and decline in clock drawing performance (B(107)=0.601, p=0.071). ConclusionsOlder people with mild to moderate dementia demonstrate significant decline in neuropsychological, physical and functional performance over one year. Baseline gait speed is associated with decline in executive function over one year, suggesting shared pathways/pathology between gait and cognition.

Functional magnetic resonance imaging response as an early biomarker of cognitive decline in elderly patients with metabolic syndrome

ObjectivesWe assessed whether potential changes in brain activation patterns of elderly individuals with metabolic syndrome (MetS) who were cognitively healthy (without mild cognitive impairment or dementia) were associated with cognitive decline in executive function in the short-term. MethodWe analyzed 43 individuals (23 MetS, 20 controls) using a global geriatric evaluation, a neuropsychological battery, and task-related (attention) fMRI exam. Correlation analysis between the fMRI signal at baseline and cognitive impairment after 1year was based on the voxel-based Pearson coefficient, corrected for multiple comparisons. ResultsAt baseline, MetS patients showed reduced brain response in frontal and parietal regions compared to controls. After one year, the MetS group also showed a decline in verbal fluency performance. fMRI response in the right dorsolateral prefrontal cortex and bilateral parietal lobes was negatively correlated with verbal fluency decline in the MetS group. DiscussionOur results provide an early biomarker of the possible development of cognitive impairment, particularly in the executive function, of elderly individuals suffering from MetS. These findings also point to an up or down regulation which could be interpreted as compensatory mechanism for possible brain tissue burden caused by MetS.

LONELINESS, VERBAL FLUENCY, AND SOCIAL ENGAGEMENT OVER TIME: A MEDIATION ANALYSIS

Background Lonely individuals are more likely to socially withdraw, an effect attributed to social distrust and preference for solitude (Ernst and Cacioppo, 2000). However, it is alternatively possible that loneliness causes cognitive deficits, which in turn precipitate social withdrawal. Loneliness has been shown to be associated with decreased verbal fluency in the literature (Schnittger et al., 2012; Boss, 2015; Shankar et al., 2013). We wanted to investigate whether loneliness a) was related to changes in social engagement over time, and b) predicted verbal fluency, which in turn precedes social withdrawal, possibly due to communicative difficulties. Methods Data from 4715 participants who were not institutionalised, did not have dementia at baseline, and were involved in waves 3, 4, and 5 of the English Longitudinal Study of Ageing (ELSA), were used. Residualised change scores were calculated to evaluate changes in engagement in social activity between waves 3 and 5. A mediation model (within a Structural Equation Modelling framework) was used to evaluate whether verbal fluency (measured using an animal naming task at wave 4) mediated the association between loneliness at wave 3 (measured using the UCLA Loneliness scale; Russell, 1996) and residualised change scores in engagement in social activities between waves 3 and 5. Results Overall, engagement in social activities decreased from a median of 3 activities to 2 activities between waves 3 and 5. This change was predicted by both loneliness (Beta = -0.056, p<0.001) and verbal fluency (beta = 0.083, p<0.001) such that loneliness predicted a decrease and verbal fluency an increase in social engagement. Verbal fluency was a mediator of the association between loneliness and changes in social engagement between waves (indirect effect = -0.009, p<0.001). Conclusions Results support the hypothesis that loneliness leads to a decrease in social engagement (possibly equivalent to social withdrawal), partly due to cognitive decline in verbal fluency. Results have implications for theoretical understanding of loneliness. Theories of loneliness alternately suggest that it is a motivational state to improve likelihood of engaging with others, and that it is a pathology that leads to social withdrawal. The current findings go some way towards elucidating this issue.

Subthalamic Nuclei Stimulation in Patients With Pantothenate Kinase-Associated Neurodegeneration (PKAN)

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disease that leads to extrapyramidal symptoms, such as dystonia, ataxia, dysarthria, and involuntary movements. Treatment of PKAN with deep brain stimulation (DBS) has been reported, but mainly focuses on targeting the globus pallidus internus (GPi). Subthalamic nuclei (STN) may also be a potential target for treatment of PKAN. In this study, we reviewed three patients with PKAN (two with typical PKAN and one with atypical PKAN) treated by bilateral STN stimulation and present a review of the literature. All patients received neurological evaluation using the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS) scoring system before and after surgery. Patients were then subject to regular clinical follow-ups (ranging from 22 to 44 months). The mean stimulation amplitude, pulse width and frequency was 2.65 ± 0.45 V, 91.7 ± 21.9 μs, and 146.7 ± 12.5 Hz, respectively. BFMDRS scores were improved in all patients after surgery, ranging from 41.6 to 73.1%. Improvements of appendicular symptoms ranged from 46.2 to 94.1%, and improvements of axial symptoms ranged from 27.3 to 33.3%. No side effects were reported in patients 1 and 2; whereas patient 3 exhibited a mild decline in verbal fluency one year after surgery. STN stimulation could serve as a candidate DBS target in the treatment of PKAN, especially for patients with prominent appendicular symptoms.

Insulin Resistance Predicts Cognitive Decline: An 11-Year Follow-up of a Nationally Representative Adult Population Sample.

The aim of this study was to examine whether insulin resistance, assessed by HOMA of insulin resistance (HOMA-IR), is an independent predictor of cognitive decline. The roles of HOMA-IR, fasting insulin and glucose, HbA1c, and hs-CRP as predictors of cognitive performance and its change were evaluated in the Finnish nationwide, population-based Health 2000 Health Examination Survey and its 11-year follow-up, the Health 2011 study (n = 3,695, mean age at baseline 49.3 years, 55.5% women). Categorical verbal fluency, word-list learning, and word-list delayed recall were used as measures of cognitive function. Multivariate linear regression analysis was performed and adjusted for previously reported risk factors for cognitive decline. Higher baseline HOMA-IR and fasting insulin levels were independent predictors of poorer verbal fluency performance (P = 0.0002 for both) and of a greater decline in verbal fluency during the follow-up time (P = 0.004 for both). Baseline HOMA-IR and insulin did not predict word-list learning or word-list delayed recall scores. There were no interactions between HOMA-IR and apolipoprotein E ε4 (APOEε4) genotype, hs-CRP, or type 2 diabetes on the cognitive tests. Fasting glucose and hs-CRP levels at baseline were not associated with cognitive functioning. Our results show that higher serum fasting insulin and insulin resistance predict poorer verbal fluency and a steeper decline in verbal fluency during 11 years in a representative sample of an adult population. Prevention and treatment of insulin resistance might help reduce cognitive decline later in life.

Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression

Late-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. Age at depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response) were examined. In a longitudinal study of late-life depression in an academic center, 273 depressed and 164 never-depressed community-dwelling elders aged 60 years or older were followed on average for over 5 years. Participants completed annual neuropsychological testing. Neuropsychological measures were converted to z-scores derived from the baseline performance of all participants. Cognitive domain scores at each time were then created by averaging z-scores across tests, grouped into domains of episodic memory, attention-working memory, verbal fluency, and executive function. Depressed participants exhibited poorer performance at baseline and greater subsequent decline in all domains. Early-onset depressed individuals exhibited a greater decline in all domains than late-onset or nondepressed groups. For remission, remitters and nonremitters at both 3 and 12 month exhibited greater decline in episodic memory and attention-working memory than nondepressed subjects. Three-month remitters also exhibited a greater decline in verbal fluency and executive function, whereas 12-month nonremitters exhibited greater decline in executive function than other groups. Consistent with past studies, depressed elders exhibit greater cognitive decline than nondepressed subjects, particularly individuals with early depression onset, supporting the theory that repeated depressive episodes may contribute to decline. Clinical remission is not associated with less cognitive decline.

Apathy and Reduced Speed of Processing Underlie Decline in Verbal Fluency following DBS.

Objective. Reduced verbal fluency is a strikingly uniform finding following deep brain stimulation (DBS) for Parkinson's disease (PD). The precise cognitive mechanism underlying this reduction remains unclear, but theories have suggested reduced motivation, linguistic skill, and/or executive function. It is of note, however, that previous reports have failed to consider the potential role of any changes in speed of processing. Thus, the aim of this study was to examine verbal fluency changes with a particular focus on the role of cognitive speed. Method. In this study, 28 patients with PD completed measures of verbal fluency, motivation, language, executive functioning, and speed of processing, before and after DBS. Results. As expected, there was a marked decline in verbal fluency but also in a timed test of executive functions and two measures of speed of processing. Verbal fluency decline was associated with markers of linguistic and executive functioning, but not after speed of processing was statistically controlled for. In contrast, greater decline in verbal fluency was associated with higher levels of apathy at baseline, which was not associated with changes in cognitive speed. Discussion. Reduced generativity and processing speed may account for the marked reduction in verbal fluency commonly observed following DBS.

Diffusion tensor imaging predicts cognitive function change following partial brain radiotherapy for low-grade and benign tumors

Purpose/objectivesRadiation injury to parahippocampal cingulum white matter is associated with cognitive decline. Diffusion tensor imaging (DTI) detects micropathologic changes in white matter. Increased radial diffusion (RD) and decreased axial diffusion (AD) correspond to demyelination and axonal degeneration/gliosis respectively. We aimed to develop a predictive model for radiation-induced cognitive changes based upon DTI changes. Materials/methodsTwenty-seven adults with benign or low-grade tumors received partial brain radiation therapy (RT) to a median dose of 54Gy. Patients underwent DTI before RT, during RT, and at the end of RT. Cognitive testing was performed before RT, and 6 and 18months after RT. Parahippocampal cingulum white matter was contoured to obtain mean values of AD and RD. ResultsBy univariate analysis, decreasing AD and increasing RD during RT predicted declines in verbal memory and verbal fluency. By multivariate analysis, baseline neurocognitive score was the only clinical variable predicting verbal memory change; no clinical variables predicted verbal fluency change. In a multivariate model, increased RD at the end of RT significantly predicted decline in verbal fluency 18months after RT. ConclusionsImaging biomarkers of white matter injury contributed to predictive models of cognitive function change after RT.

INSULIN RESISTANCE IS ASSOCIATED WITH A DECLINE IN VERBAL FLUENCY DURING 11 YEARS OF FOLLOW-UP

INSULIN RESISTANCE IS ASSOCIATED WITH A DECLINE IN VERBAL FLUENCY DURING 11 YEARS OF FOLLOW-UP

Neuropsychiatric consequences of deep brain stimulation surgeries in the patients affected by chronic movement disorders: A brief report

The main surgical procedure for PD and other chronic movement disorders is deep brain stimulation. DBS has been reported to have specific consequences such as decline in verbal fluency and episodes of depression.We designed an interventional study in 12 patients affected by Parkinson, dystonia and tic who underwent DBS surgery. Patient assessed before surgery, one month and one year after surgery.The results proved a significant improvement in SF36. The Hamilton's anxiety scale showed an overall but insignificant improvement. The mean of scores of the BDI had a great drop one month after surgery but a raise at the 12th month (insignificant pattern).Pearson's correlation test showed a significant negative correlation between age and the SF36 scores. The BDI's scores were assessed in relation with age. Although there was no actual relation between them before surgery, we detected a positive correlation between them after one year.ConclusionThe pattern of changes can be related with the differences between perioperative expectations and real long-term outcomes. Correlations between changes seen in BDI and SF36 scores with age can be considered as a confirmatory evidence for this idea.All cases showed an insignificant gradual decline in digit span test, which may be independent of the surgical procedure. Although the COWA test could not prove a significant deterioration in verbal fluency but a slight decline after one year was obvious, in addition to one patient who turned aphasic during this period.The outcomes showed that the benefits of DBS outweigh the slight risk of developing depression.Disclosure of interestThe authors have not supplied their declaration of competing interest.

ID 77 – Confounding effect of age on verbal fluency after deep brain stimulation to the subthalamic nucleus (DBS-STN) in Parkinson’s disease

Background Deep brain stimulation (DBS) is commonly used in the treatment of Parkinson’s disease (PD). Various research groups have reported that DBS is associated with decreased verbal fluency. We investigated the possible confounding effects of patients’ age, disease duration and levodopa equivalent daily dose (LEDD) on verbal fluency performance after DBS in patients with PD. Methods 43 patients with PD and without major psychiatric illness (according to DSM-IV) were enrolled in the study, median age 63.4 years, range 39–76. Subjects were allocated to two groups: the first were scheduled to bilateral DBS-STN (n = 21), the second comprised patients without DBS surgery (n = 22). Verbal fluency performance in both groups was assessed with Controlled Oral Word Association Test at baseline and eight months later. Results Decline in semantic fluency performance was found in the DBS group (p = 0.03). No confounding effect of age, disease Duration and LEDD was found in relation to this decline. Conclusions This restrospective observation confirms previous findings showing a decline in verbal fluency after DBS-STN in PD patients when compared with PD patients without surgery. Verbal fluency decline is unrelated to age, disease duration and LEDD.

Verbal Fluency in Parkinson's Patients with and without Bilateral Deep Brain Stimulation of the Subthalamic Nucleus: A Meta-analysis.

Patients with Parkinson's disease often experience significant decline in verbal fluency over time; however, deep brain stimulation of the subthalamic nucleus (STN-DBS) is also associated with post-surgical declines in verbal fluency. The purpose of this study was to determine if Parkinson's patients who have undergone bilateral STN-DBS have greater impairment in verbal fluency compared to Parkinson's patients treated by medication only. A literature search yielded over 140 articles and 10 articles met inclusion criteria. A total of 439 patients with Parkinson's disease who underwent bilateral STN-DBS and 392 non-surgical patients were included. Cohen's d, a measure of effect size, was calculated using a random effects model to compare post-treatment verbal fluency in patients with Parkinson's disease who underwent STN-DBS versus those in the non-surgical comparison group. The random effects model demonstrated a medium effect size for letter fluency (d=-0.47) and a small effect size for category fluency (d=-0.31), indicating individuals with bilateral STN-DBS had significantly worse verbal fluency performance than the non-surgical comparison group. Individuals with Parkinson's disease who have undergone bilateral STN-DBS experience greater deficits in letter and category verbal fluency compared to a non-surgical group.

Is the left uncinate fasciculus associated with verbal fluency decline in mild Alzheimer's disease?

The association between verbal fluency deficit in Alzheimer's disease (AD) and deterioration of specific white matter (WM) tracts is currently not well understood. Using diffusion tensor imaging, we investigated a possible association between the left uncinate fasciculus, which has been implicated in word retrieval, and verbal fluency deficit in AD. A comparison of five properties of WM (fractional anisotropy, mode of anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) in 28 mild AD patients and 26 age-, gender- and education-matched healthy controls revealed significant group differences in a range of WM tracts. Looking specifically at diffusion parameters’ values for the left uncinate fasciculus and verbal fluency scores in the AD group, we observed a positive trend between the letter fluency scores and mode of anisotropy values (r = 0.36, p = 0.55). Thus, our data suggest more global WM damage in mild AD, which also includes damage to the left uncinate fasciculus. However, damage to this particular tract is not robustly associated with verbal fluency decline at this stage of disease.

Neuropsychiatric Consequences of Deep Brain Stimulation in Patients with Chronic Movement Disorders.

Nowadays, the main surgical treatment for Parkinson disease (PD) and other chronic movement disorders is deep brain stimulation (DBS), which has been reported to have consequences such as decline in verbal fluency and episodes of depression. We designed an interventional study in 12 patients (9 men, 3 women) affected by PD, dystonia, and tic who underwent bilateral subthalamic nucleus (STN) DBS operation. We assessed each patient before surgery, 1 month, and then 1 year after the operation. The results of our study showed a significant improvement with respect to the scores of the Short Form Health Survey (SF36). The Hamilton anxiety scale also showed an overall but insignificant improvement. The mean scores of the Beck depression inventory had a great drop 1 month after operation but a rise 12 months later, through an overall insignificant pattern. Pearson correlation test showed a significant negative correlation between age and the changes of the SF36 scores. The BDI scores were assessed in relation with age. Although there was no actual relation between them before the operation, we detected a positive correlation between them 1 year after the DBS. The results of our study were generally compatible with the results of Drapier et al. (2006), Heo et al. (2008), York et al. (2009), Paek et al. (2013), and amazingly similar to the meta-analysis published by Couti (2014) reporting an improvement in the mood of patients postoperatively that declines gradually with time. Is it possible to conclude that these changes are related with the differences between pre-operative expectations and real long-term outcomes? Correlations between changes seen in BDI and SF36 scores with age can be considered as a confirmatory evidence for this argument. All cases showed an insignificant gradual decline in digit span test, which may be independent of the operation, according to the studyof York (2009). Although the Controlled Oral Word Association (COWA) test could not prove a significant deterioration in verbal fluency but a slight decline after 1 year was obvious, besides one patient who turned aphasic during this period. These results resemble the outcomes of the studies of Contarino et al. (2007) and York et al. (2009). The outcomes showed that the benefits of DBS outweighs the slight risk of developing depression; However, patients especially the elderly must be under regular monitoring for early detection of mood changes. Adverse effect on verbal fluency is another important issue to be considered while evaluating the cost benefits of the operation. Thus ethically patients should be made aware of this potential risk before decision making. According to negative correlation between the improvement in the quality of life and age, and the significant relationship between age and higher BDI scores, we strongly suggest that age be considered as a determinant factor in case selection.

Deep Brain Stimulation Frequency of the Subthalamic Nucleus Affects Phonemic and Action Fluency in Parkinson's Disease.

Introduction. Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) has been linked to a decline in verbal fluency. The decline can be attributed to surgical effects, but the relative contributions of the stimulation parameters are not well understood. This study aimed to investigate the impact of the frequency of STN-DBS on the performance of verbal fluency tasks in patients with PD. Methods. Twenty individuals with PD who received bilateral STN-DBS were evaluated. Their performances of verbal fluency tasks (semantic, phonemic, action, and unconstrained fluencies) upon receiving low-frequency (60 Hz) and high-frequency (130 Hz) STN-DBS were assessed. Results. The performances of phonemic and action fluencies were significantly different between low- and high-frequency STN-DBS. Patients showed a decrease in these verbal fluencies for high-frequency STN-DBS. Conclusion. Low-frequency STN-DBS may be less harmful to the verbal fluency of PD patients.

Negative perceptions of aging predict longitudinal decline in cognitive function.

Perceptions of aging have been shown to impact the psychological and physical health of older adults. Experimental studies have found that priming older adults with negative attitudes toward aging results in immediate declines in psychological, physical and cognitive functions. Longitudinal studies have supported this work illustrating the longer term impact of negative and positive perceptions of aging on psychological and physical health. However, it is surprising that there are a limited number of studies that have investigated the longitudinal association between perceptions of aging and cognitive function. The aim of this article is therefore to explore the association between perceptions of aging and cognitive function across a number of domains in a population representative sample of adults aged 50 and older. The sample was assessed twice over 2 years. Negative perceptions of aging at baseline were independently associated with longitudinal decline in verbal fluency and self-rated memory over a 2-year period after adjustment for physical and mental health. These findings suggest that negative perceptions of aging may play a role in cognitive decline in the older population. Furthermore, aging perceptions may be a modifiable factor to target for future interventions.

The Verbal Fluency Decline After Deep Brain Stimulation in Parkinson's Disease: Is There an Influence of Age?

DBS is commonly used to treat Parkinson's disease (PD). DBS is not considered to cause major cognitive side effects, but some research groups have reported that it can cause decreased verbal fluency. The influence of age on DBS cognitive outcome is unclear. We investigated the possible influence of patients' age, level of education, disease duration, disease progression, depression, and levodopa equivalent dose (LED) on verbal fluency performance in patients with PD who underwent DBS of the subthalamic nucleus (STN-DBS). In this article, we investigated the influence of demographic and clinical parameters, especially age, on cognitive performance post-DBS in PD patients. Forty-three patients with PD and without major psychiatric illness (according to Diagnostic and Statistical Manual of Mental Disroders, Fourth Edition) were enrolled in the study. Median age was 64.0 years (range, 46-77). In 21 patients, the indication for DBS was established on clinical grounds in keeping with international guidelines; these patients underwent STN-DBS, and the remaining 22 did not. Cognitive performance in both groups was assessed by standard neuropsychological test batteries at baseline and after median follow-up of 7 months. A statistically significant decline in the semantic category of verbal fluency task was found in the STN-DBS group (P < 0.01). Linear regression model revealed an influence of age (P < 0.01) and disease duration (P < 0.01) in relation to this decline. This study confirms previous findings that verbal fluency declines after STN-DBS in PD patients in comparison to PD patients without DBS. This decline is related to age and disease duration.

Association of Alzheimer's related genotypes with cognitive decline in multiple domains: results from the Three-City Dijon study.

Several genetic polymorphisms have been associated with Late Onset Alzheimer's Disease (LOAD), but there has been limited evidence on whether these polymorphisms predict intermediary stage outcomes such as cognitive changes in prospective community-based studies. Our aim was to evaluate whether polymorphisms previously established as predictors of LOAD also predict worse cognitive function and accelerated decline across multiple cognitive domains. We analyzed data from the 3C-Dijon study, in which 4931 respondents aged 65+ were examined up to 5 times over 10 years with a neuropsychological assessment. We evaluated the associations of polymorphisms in APOE, CR1, BIN1, CLU, PICALM, ABCA7, MS4A6A, CD33, MS4A4E and CD2AP with level and change in 5 neuropsychological tests, assuming a dominant effect model. To optimize measurement, we used a mixed regression model with a latent process for each cognitive domain: global cognition (Mini Mental State Examination); verbal fluency (Isaac's Set Test); visual memory (Benton Visual Retention Test); information processing (Trail Making Test B) and literacy (National Adult Reading Test). APOE was associated with accelerated decline in global cognition and verbal fluency. Only two non-APOE genetic polymorphisms were associated with cognitive decline: CR1 was associated with rate of change in verbal fluency and BIN1 was associated with rate of change in global cognition. In a large prospective population-based study of dementia-free individuals, only a few cognitive domains were associated with established LOAD risk alleles. The most consistent associations were for global cognition and verbal fluency.