The Hopkins Verbal Learning Test (HVLT) has been validated for detecting dementia in English-speaking populations. However, no studies have examined the Chinese version of the HVLT scale, and appropriate cut-off scores for dementia in the Chinese population remain unclear.
631 subjects aged 60 and over were recruited at a memory clinic at Dongzhimen Hospital in Beijing. Of these, 249 were classified as exhibiting normal cognition (NC), 134 were diagnosed with mild cognitive impairment (MCI), 97 were diagnosed with Alzheimer’s disease (AD), 14 met the diagnosis for vascular dementia (VaD), and 50 were diagnosed with other types of dementia, including mixed dementia. The discriminative capacity of the HVLT total learning score, recognition score and total score were calculated to determine their sensitivity and specificity for detecting MCI, AD and other dementias, and various cut-off scores.
HVLT scores were affected by age, education and sex. The HVLT total learning score exhibited an optimal balance between sensitivity and specificity using a cut-off score of 15.5 for distinguishing AD and other types of dementia from NC using the ROC curve, with sensitivity of 94.7% for distinguishing AD and all types of dementia, and specificity of 92.5% for detecting AD and 93.4% for detecting all types of dementias. We stratified the AD and MCI groups by age, and calculated the validity in each age group. In the 50–64 years age group, when the cutoff score was 18.5, the sensitivity of 0.955 and specificity of 0.921 were obtained for discriminating the NC and AD groups, and in the 65–80 years group, and optimal sensitivity and specificity values (0.948 and 0.925, respectively) were obtained with a cutoff score of 14.5.
When the cutoff score was 21.5 in HVLT total recall, an optimal balance was obtained between sensitivity and specificity (69.1% and 70.7%, respectively) in distinguishing MCI from NC.
A cut-off score of 15.5 in the HVLT total learning score led to high discriminative capacity between the dementia and NC groups. This suggests that the HVLT total learning score can provide a useful tool for discriminating dementia, but not MCI, from NC in clinical and epidemiological practice.
Alzheimer’s dementia; Mild cognitive impairment; Hopkins verbal learning test; Screening test
Data from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial (N=2,802) were analyzed to examine whether word list learning predicts future everyday functioning. Using stepwise random effects modeling, measures from the modified administrations of the Hopkins Verbal Learning Test (HVLT) and the Auditory Verbal Learning Test (AVLT) were independently predictive of everyday IADL functioning, problem-solving, and psychomotor speed. Associations between memory scores and everyday functioning outcomes remained significant across follow-up intervals spanning five years. HVLT total recall score was consistently the strongest predictor of each functional outcome. Results suggest that verbal memory measures are uniquely associated with both current and future functioning and that specific verbal memory tests like the HVLT and AVLT have important clinical utility in predicting future functional ability among older adults.
functional ability; HVLT; AVLT; verbal memory
A pattern characterizing cognitive deficits in mild stroke could help in differential diagnosis and rehabilitation planning.
Fifty patients with mild stroke (modified Rankin scale ≤2 at discharge) aged >60 years were given the Mini Mental State Examination (MMSE), the Hopkins Verbal Learning Test-Revised (HVLT-R) and the Stroop test.
On HVLT-R, significant impairments were found in learning and recall, but not in delayed recall. The Stroop test revealed significant impairments in reading speed, but not in color-word interference. Using the MMSE, significant deficits were only found in the youngest age group.
Elderly patients with mild stroke show deficits in verbal learning/recall and in reading speed, but not in the MMSE, delayed recall or color-word interference. The deficits are consistent with a mild-to-moderate brain dysfunction, with relative sparing of medial brain structures.
Color-word interference; Learning; Memory; Mental state; Mild stroke
This study tests the hypothesis that the use of a semantic organizational strategy, during the free recall phase of a verbal memory task predicts remission of geriatric depression.
65 elderly patients with major depression participated in a 12-week escitalopram treatment trial. Neuropsychological performance was assessed at baseline after a 2-week drug washout period. The Hopkins Verbal Learning Test-Revised (HVLT-R)(Brandt 2001) was used to assess verbal learning and memory. Remission was defined as a Hamilton Depression Rating Scale Score (HDRS) less than or equal to 7 for two consecutive weeks and no longer meeting DSM-IV-TR criteria for major depression. The association between the number of clusters used at the final learning trial (Trial 3) and remission was examined using Cox’s proportional hazards survival analysis. The relationship between the number of clusters utilized in the final learning trial and words recalled after a 25 minute delay was examined in a regression with age and education as covariates.
Greater number of clusters utilized predicted remission rate (Hazard ratio (95% CI) = 1.26 (1.04–1.54), χ2 =4.23, df=3, p=0.04). There was a positive relationship between the total number of clusters used by the end of the third learning trial and the total number of words recalled at the delayed recall trial (F(3,58)=7.93;p<.001)
Effective semantic strategy use at baseline on a verbal list learning task by elderly depressed patients was associated with greater rate of remission with antidepressant treatment. This result provides support for previous findings indicating that measures of executive functioning at baseline are useful in predicting antidepressant response.
Executive function; geriatric; depression; remission; semantic strategy; Hopkins Verbal Learning Test-Revised (HVLT)
Groups of patients with Hungington's disease and probable dementia of Alzheimer type (DAT) matched for level of dementia on the basis of mini mental state examination scores were compared in several tests of visual memory and tests sensitive to frontal lobe dysfunction. Whereas recall of patients with DAT tended to be worse on the Kendrick object learning test, the two groups were equivalent on tests of sensorimotor ability and delayed matching to sample performance. By contrast, the patients with Huntington's disease were significantly worse on tests of pattern and spatial recognition, simultaneous matching to sample, visuospatial paired associates, and on three tests sensitive to frontal lobe dysfunction--namely, the Tower of London test of planning, spatial working memory, and a visual discrimination learning and reversal paradigm. The impairments in these tests, however, did not always qualitatively resemble those seen in patients with frontal lobe damage and may be more characteristic of primary neostriatal deficit. In the visual discrimination paradigm the patients with Hungtington's disease were significantly worse than the patients with DAT at the simple reversal stage, where they displayed significant preservation to the previously rewarded alternative. The results are consistent with the hypothesis that patients with Huntington's disease exhibit deficits in tests sensitive to frontostriatal dysfunction and that this form of intellectual deterioration is qualitatively distinct from that seen in Alzheimer's disease.
Objective: To determine whether a differential impairment of spatial memory exists in Huntington's disease (HD).
Methods: Patients with HD and age matched neurologically normal subjects, as well as patients with Alzheimer's disease (AD) and Parkinson's disease (PD), learned the locations of nine items on a 3x3 grid over as many as 10 trials. Delayed recall of the items and their spatial locations was tested.
Results: Patient with HD performed worse than normal subjects on all measures, and intermediate between AD and PD patients. However, they were the only subject group in whom delayed recall of spatial locations was poorer than delayed recall of object identity. This effect was independent of the severity of dementia.
Conclusions: HD patients have a differential impairment in memory for object–location information. This finding may relate to the involvement of the caudate nucleus, the primary site of pathology in HD, in corticostriatal circuits linking it with parietal association cortex. It is also consistent with views of the dorsal striatum as responsible for the acquisition over trials of specific place responses.
To determine the validity of standardized screening assessments of cognitive functioning to detect neuropsychological impairment evaluated using a comprehensive battery in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
This is a cross-sectional study using a combined cohort of 139 persons with SLE and 82 persons with RA. Screening cut points were empirically derived using receiver operating characteristic curves and threshold selection methods. Screening measures included the Hopkins Verbal Learning Test-Revised (HVLT-R) learning and delayed recall indices and phonemic fluency, a composite measure of the 3 cognitive screening tests, and the Perceived Deficits Questionnaire-Short Form (PDQ-SF), a self-report measure of cognitive symptoms. A comprehensive neuropsychological battery was administered as the “gold standard” index of neuropsychological impairment.
Rates of neuropsychological impairment were 27% and 15% for the SLE and RA cohorts, respectively. Optimal threshold estimations were derived for 5 screening techniques. The HVLT-R learning and phonemic fluency indices yielded the greatest sensitivity at 81%. The PDQ-SF yielded the lowest sensitivity at 52%. All measures were significantly associated with neuropsychological impairment after controlling for relevant sociodemographic covariates and depression.
These results suggest that telephone-administered screening techniques may be useful measures to identify persons with neuropsychological impairment. Specifically, measures of phonemic fluency and verbal learning appeared to be most sensitive and least likely to misclassify impaired individuals as cognitively intact. Self-reported questionnaires may have relatively decreased sensitivity compared to standardized interviewer-administered cognitive measures.
Episodic memory tasks are one of the most sensitive tools to discriminate Alzheimer’s disease (AD). This study aimed to validate a shorter version verbal memory test that will efficiently assess Chinese elderly with memory complaints. One hundred and eighty-five elderly with normal cognition (NC) and 217 AD patients were evaluated. Each participant received the Chinese Version Verbal Learning Test (CVVLT) consisting of 9 two-character nouns with 4 learning trials, 2 delayed recalls in 30 seconds and 10 minutes, and a word recognition test. In the NC elderly, age and sex had significant effects on recall scores in CVVLT, while education level showed an inverse correlation with 3 different patterns of errors made during the learning, recall, and recognition trials. AD patients had lower scores across all recall tests. In those with lower educational level, NC elderly had higher perseveration errors than AD patients. The cutoff value between the AD and NC groups in the 10-minute recall was 4/5 for those aged >75 years and 5/6 for those aged <75 years. This study has good validity in discriminating AD participants and the data here can help in diagnosing AD and mild cognitive impairment using the CVVLT.
Chinese Verbal Learning Test; education; memory; dementia; cutoff value; validation
This study compared verbal learning and memory in patients with autopsy-confirmed dementia with Lewy Bodies (DLB) and patients with Parkinson's disease with dementia (PDD). Twenty-four DLB patients, 24 PDD patients, and 24 normal comparison participants were administered the California Verbal Learning Test. The three groups were matched on demographic variables and the two patient groups were matched on the Mattis Dementia Rating Scale. The results indicated that DLB patients recalled less information than PDD patients on all but one recall measure and displayed a more rapid rate of forgetting. In contrast, the PDD patients committed a greater percent of perseveration errors than the DLB patients. The two groups did not differ in the percentage of recall intrusion errors or any measures of recognition. A discriminant function analysis (DFA) using short delay cued recall, percent perseveration errors, and list b recall, differentiated the DLB and PDD groups with 81.3% accuracy. The application of the DFA algorithm to another sample of 42 PDD patients resulted in a 78.6% correct classification rate. The results suggest that, despite equivalent levels of general cognitive impairment, patients with DLB or PDD exhibit a different pattern of verbal learning and memory deficits.
Patients seeking deep brain stimulation (DBS) surgery for Parkinson’s disease (PD) typically undergo neuropsychological assessment to determine candidacy for surgery, with poor memory performance interpreted as a contraindication. Patients with PD may exhibit worse memory for word lists than for stories due to the lack of inherent organization in a list of unrelated words. Unfortunately, word list and story tasks are typically developed from different normative datasets, and the existence of a memory performance discrepancy in PD has been challenged. We compared recall of stories and word lists in 35 non-demented PD candidates for DBS. We administered commonly-used neuropsychological measures of word list and story memory (Hopkins Verbal Learning Test, Logical Memory), along with a second word list task that was co-normed with the story task. Age-corrected scores were higher for the story task than for both word list tasks. Compared to story recall, word list recall correlated more consistently with motor severity and composite measures of processing speed, working memory, and executive functioning. These results support the classic view of fronto-subcortical contributions to memory in PD and suggest that executive deficits may influence word list recall more than story recall. We recommend a multi-componential memory battery in the neuropsychological assessment of DBS candidates to characterize both mesial temporal and frontal-executive memory processes. One should not rely solely on a word list task because patients exhibiting poor memory for word lists may perform better with stories and therefore deserve an interdisciplinary discussion for DBS surgery.
Cognitive dysfunction and cardiovascular disease are common and debilitating manifestations of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between cardiovascular events, traditional cardiovascular risk factors, and SLE-specific risk factors as predictors of cognitive dysfunction in a large cohort of participants with SLE.
Subjects included 694 participants from the Lupus Outcomes Study (LOS), a longitudinal study of SLE outcomes based on annual telephone survey querying demographic and clinical variables. The Hopkins Verbal Learning Test – Revised (HVLT-R) and the Controlled Oral Word Association Test (COWAT) were administered to assess cognitive function. Multiple logistic regression was used to identify cardiovascular events (myocardial infarction (MI), stroke), traditional cardiovascular risk factors (hypertension, hyperlipidemia, diabetes, obesity, smoking), and SLE-specific risk factors (antiphospholipid antibodies (aPL), disease activity, disease duration) associated with cognitive impairment in year seven of the LOS.
The prevalence of cognitive impairment as measured by verbal memory and verbal fluency metrics was 15%. In adjusted multiple logistic regression analyses, aPL (OR=2.10, 95% CI 1.3-3.41), hypertension (OR=2.06, 95% CI 1.19-3.56), and a history of stroke (OR=2.27, 95% CI 1.16-4.43) were significantly associated with cognitive dysfunction. In additional analyses evaluating the association between these predictors and severity of cognitive impairment, stroke was significantly more prevalent in participants with severe impairment when compared to those with mild or moderate impairment (p=0.036).
These results suggest that the presence of aPL, hypertension, and stroke are key variables associated with cognitive impairment, which may aid in identification of patients at greatest risk.
To explore associations between two specific cognitive domains and aspects of medication management among older primary care patients.
A sample of patients aged 65+ years drawn from several small-town primary care practices was carefully characterized with cognitive testing and use of prescription medications. Two primary outcome variables were examined: (a) self reports of setting up schedules to manage their own medication, and (b) overall research assessment of adherence to prescribed medications. Predictor variables included scores on a test of verbal memory (Hopkins Verbal Learning Test, HVLT) and a test of executive functions (Part B of the Trailmaking test) presence of prescription insurance, number of medications, and dosing frequency, adjusting for age, sex, and education. Multiple logistic regression and generalized estimating equation models were used for multivariable analyses.
Higher scores on the verbal memory test and having prescription insurance were independently associated with successfully setting up a medication schedule, after adjusting for covariates. Higher scores on the test of working memory and a lower number of prescription drugs were associated with the participant being assessed as adherent to medications.
Independent cognitive processes are associated with the ability to set up a medication schedule and overall adherence to prescriptions. Better verbal memory functioning was strongly and independently associated with study participants setting up their own medication schedules, while better executive functioning was strongly and independently associated with being fully adherent to prescription instructions. Deficits in either cognitive ability could result in medication errors.
Medication adherence; elderly; cognition
Deficits in learning, memory, and executive functions are common cognitive sequelae of Parkinson's disease with dementia (PDD) and Alzheimer's disease (AD); however, the pattern of deficits within these populations is distinct. Hierarchical regression was used to investigate the contribution of two measures with executive function properties (Verbal Fluency and CLOX) on list-learning performance (CVLT-II total words learned) in a sample of 25 PDD patients and 25 matched AD patients. Executive measures were predictive of list learning in the PDD group after the contribution of overall cognition and contextual verbal learning was accounted for, whereas in the AD group the addition of executive measures did not add to prediction of variance in CVLT-II learning. These findings suggest that deficits in executive functions play a vital role in learning impairments in patients with PDD; however, for AD patients, learning difficulties appear relatively independent of executive dysfunction.
Parkinson's disease with dementia; Alzheimer's disease; Executive function; List learning; Neuropsychologic tests; Comparative studies
Overactive bladder (OAB) is a common condition affecting the elderly. The mainstay of treatment for OAB is medical therapy with anticholinergics. However, adverse events have been reported with this class of drugs including cognitive changes.
To investigate the effect of an anticholinergic medication on cognitive function in postmenopausal women being treated for OAB.
Prospective cohort study conducted from January to December 2010, with 12-week follow-up after medication initiation.
Urogynecology clinic at one academic medical center.
Women age 55 or older seeking treatment for OAB and opting for anticholinergic therapy were recruited.
Baseline cognitive function was assessed via the Hopkins Verbal Learning Test – Revised Form (HVLT-R) (and its 5 subscales), the Orientation, Memory & Concentration (OMC) short form, and the Mini-Cog evaluation. After initiation of trospium chloride extended release, cognitive function was reassessed at Day 1, Week 1, Week 4 and Week 12. Bladder function was assessed via three condition-specific quality of life questionnaires. Secondary outcomes included change in bladder symptoms, correlation between cognitive and bladder symptoms, and overall medication compliance.
Main Outcome Measure
Change in HVLT-R score at Week 4 after medication initiation, compared to baseline (pre-medication) score.
Of 50 women enrolled, 35 completed the assessment. Average age was 70.4 years and 77.1% had previously taken anticholinergic medication for OAB. At enrollment 65.7% had severe overactive bladder and 71.4% had severe urge incontinence. Cognitive function showed an initial decline on Day 1 in HVLT-R total score (p=0.037), HVLT-R Delayed Recognition subscale (p=0.011) and HVLT-R Recognition Bias subscale (p=0.01). At Week 1 the HVLT-R Learning subscale declined from baseline (p=0.029). All HVLT-R scores normalized by Week 4. OMC remained stable throughout. The Mini-Cog nadired at a 90.9% pass rate at Week 4. OAB symptoms did not improve until Week 4, based on questionnaire scores (p<0.05).
Cognitive function exhibited early changes after initiation of trospium chloride but normalized within four weeks. Cognitive changes occurred weeks prior to OAB symptom improvement. Surveillance for cognitive changes with anticholinergic use should be part of OAB management.
Anticholinergic; Cognitive Function; Elderly; Overactive Bladder
The purpose of the present investigation was to determine the relationship between serum ghrelin concentrations, adiposity, and verbal learning in a group of healthy, fit older adults. Participants were 28 healthy older adults (age: 70.8 ± 9.3 yrs, BMI: 27.3 ± 5.7). Participants reported to the laboratory and basic anthropometric data were collected, followed by a blood draw to quantify serum ghrelin. Participants then underwent cognitive testing that included the revised Hopkins Verbal Learning Test (HVLT), as well as the Mini-Mental Status Exam (MMSE). The results of the MMSE test revealed that the volunteers were cognitively intact (MMSE 27.6 ± 1.8). A significant correlation emerged between serum ghrelin concentrations, 2 trials of the HVLT (Trial 1: r = 0.316, P = 0.05; Trial 2: r = 0.395, P = 0.03), and the sum of three-site skinfold analysis (r = 0.417, P = 0.015). Based upon the aforementioned relationships, it appears that fasting levels of serum ghrelin are related to both verbal learning and adiposity in healthy, fit older adults.
Caffeine, the world’s most common psychoactive substance, is used by approximately 90% of North Americans everyday. Little is known, however, about its benefits for memory. Napping has been shown to increase alertness and promote learning on some memory tasks. We directly compared caffeine (200mg) with napping (60–90 minutes) and placebo on three distinct memory processes: declarative verbal memory, procedural motor skills, and perceptual learning. In the verbal task, recall and recognition for unassociated words were tested after a 7hr retention period (with a between-session nap or drug intervention). A second, different, word list was administered post-intervention and memory was tested after a 20min retention period. The non-declarative tasks (finger tapping task and texture discrimination task) were trained before the intervention and then retested afterwards. Naps enhanced recall of words after a 7hr and 20min retention interval relative to both caffeine and placebo. Caffeine significantly impaired motor learning compared to placebo and naps. Napping produced robust perceptual learning compared with placebo; however, naps and caffeine were not significantly different. These findings provide evidence of the limited benefits of caffeine for memory improvement compared with napping. We hypothesize that impairment from caffeine may be restricted to tasks that contain explicit information; whereas strictly implicit learning is less compromised.
The present study compared the performance of individuals with Huntington's disease (HD) and Alzheimer's disease (AD) on three types of California Verbal Learning Test–Second Edition (CVLT-II) recognition discriminability indices (RDI): Source, Novel, and Total. The HD and AD groups did not differ significantly on Source RDI (all 16 targets versus the 16 previously presented, List B, distractors). However, HD patients performed significantly better than AD patients on Total RDI (all 16 targets versus all 32 distractors) and Novel RDI (all 16 targets versus 16 new distractors). Implications of these findings on the differentiation of the memory disorders associated with HD and AD are discussed.
Episodic memory is the first and most severely affected cognitive domain in Alzheimer's disease (AD), and it is also the key early marker in prodromal stages including amnestic mild cognitive impairment (MCI). The relative ability of memory tests to discriminate between MCI and normal aging has not been well characterized. We compared the classification value of widely used verbal memory tests in distinguishing healthy older adults (n = 51) from those with MCI (n = 38). Univariate logistic regression indicated that the total learning score from the California Verbal Learning Test-II (CVLT-II) ranked highest in terms of distinguishing MCI from normal aging (sensitivity = 90.2; specificity = 84.2). Inclusion of the delayed recall condition of a story memory task (i.e., WMS-III Logical Memory, Story A) enhanced the overall accuracy of classification (sensitivity = 92.2; specificity = 94.7). Combining Logical Memory recognition and CVLT-II long delay best predicted progression from MCI to AD over a 4-year period (accurate classification = 87.5%). Learning across multiple trials may provide the most sensitive index for initial diagnosis of MCI, but inclusion of additional variables may enhance overall accuracy and may represent the optimal strategy for identifying individuals most likely to progress to dementia.
Episodic memory deficits are common in HIV infection and bipolar disorder, but patient insight into such deficits remains unclear. Thirty-four HIV-infected individuals without bipolar disorder l(HIV+/BD−) and 47 HIV+ individuals with comorbid bipolar disorder (HIV+/BD+) were administered the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised to examine objective learning/memory functioning. Subjective memory complaints were assessed via the memory subscale of the Patient’s Assessment of Own Functioning Inventory. HIV+/BD+ individuals performed poorer on tests of visual learning and visual/verbal recall compared to HIV+/BD− participants (ps<0.05). Memory complaints only predicted verbal learning (at a trend level, p=0.10) and recall (p=0.03) among the HIV+/BD− individuals. Memory complaints were not associated with memory performance within the HIV+/BD+ group (ps>0.10). Memory complaints were associated with affective symptoms in both groups. These complaints were also predictive of immunosuppression, higher unemployment, and greater dependence on Activities of Daily Living among the HIV+/BD+ individuals (ps<0.05). Awareness of memory abilities was particularly poor among HIV+/BD+ individuals (i.e., objective learning/memory did not correspond to reported complaints), which has important implications for the capacity of these individuals to engage in error-monitoring and compensatory strategies in daily life. Memory complaints are associated with depressed mood regardless of group membership. Among HIV+/BD+ individuals, these complaints may also signify worse HIV disease status and problems with everyday functioning. Clinicians and researchers should be cognizant of what these complaints indicate in order to lead treatment most effectively; use of objective neurocognitive assessments may still be warranted when working with these populations.
Self report; Infectious Diseases; Affective Disorders; Episodic Memory; Cognition
An exaggerated recency effect (i.e., disproportionate recall of last-presented items) has been consistently observed in the word list learning of patients with Alzheimer’s disease (AD). Our study sought to determine if there were similar alterations in serial position learning among asymptomatic persons at risk for AD due to parental family history.
Subjects included 623 asymptomatic middle-aged children of patients with AD (median = 53 years) and 157 control participants whose parents survived to at least age 70 without AD or other memory disorders. All participants were administered the Rey Auditory Verbal Learning Test which requires learning and recall of 15 unrelated nouns.
There was no significant difference in total words recalled between the AD children and control groups. However, compared to controls, AD children showed a significantly greater tendency to recall words from the end (recency) versus beginning (primacy) of the list. Serial position effects were unrelated to apolipoprotein allele epsilon 4 (APOE ε4) or depressive symptoms.
Asymptomatic persons at risk for AD by virtue of family history do not show a difference in total words recalled compared to controls, but exhibit a distinctly different serial position curve suggesting greater reliance on immediate as opposed to episodic memory. This is the same serial position pattern observed in mild AD, seen here in reduced severity. Longitudinal follow-up is planned to determine whether changes in serial position patterns are a meaningful marker for preclinical detection of AD.
Alzheimer’s disease; memory; serial position effect; prospective study; family history of dementia
Cognitive decline has been reported in Huntington disease (HD), as well as in the period before diagnosis of motor symptoms (i.e., pre-HD). However, the severity, frequency, and characterization of cognitive difficulties have not been well-described. Applying similar cutoffs to those used in mild cognitive impairment (MCI) research, the current study examined the rates of subtle cognitive dysfunction (e.g., dysfunction that does not meet criteria for dementia) in pre-HD.
Using baseline data from 160 non–gene-expanded comparison participants, normative data were established for cognitive tests of episodic memory, processing speed, executive functioning, and visuospatial perception. Cutoff scores at 1.5 standard deviations below the mean of the comparison group were then applied to 575 gene-expanded pre-HD participants from the observational study, PREDICT-HD, who were stratified by motor signs and genetic risk for HD.
Nearly 40% of pre-HD individuals met criteria for MCI, and individuals closer to HD diagnosis had higher rates of MCI. Nonamnestic MCI was more common than amnestic MCI. Single-domain MCI was more common than multiple-domain MCI. Within the nonamnestic single-domain subtype, impairments in processing speed were most frequent.
Consistent with the Alzheimer disease literature, MCI as a prodromal period is a valid concept in pre-HD, with nearly 40% of individuals showing this level of impairment before diagnosis. Future studies should examine the utility of MCI as a marker of cognitive decline in pre-HD.
= Alzheimer disease;
= Benton Facial Recognition Test;
= Diagnostic Confidence Level;
= Huntington disease;
= Hopkins Verbal Learning Test–Revised;
= mild cognitive impairment;
= Parkinson disease;
= Stroop Color Word Test;
= Symbol Digit Modalities Test;
= Unified Huntington's Disease Rating Scale.
Delayed recall of words in a verbal learning test is a sensitive measure for the diagnosis of amnestic mild cognitive impairment (aMCI) and early Alzheimer’s disease (AD). The relative validity of different retention intervals of delayed recall has not been well characterized. Using the Auditory Verbal Learning Test–Huashan version, we compared the differentiating value of short-term delayed recall (AVL-SR, that is, a 3- to 5-minute delay time) and long-term delayed recall (AVL-LR, that is, a 20-minute delay time) in distinguishing patients with aMCI (n = 897) and mild AD (n = 530) from the healthy elderly (n = 1215). In patients with aMCI, the correlation between AVL-SR and AVL-LR was very high (r = 0.94), and the difference between the two indicators was less than 0.5 points. There was no difference between AVL-SR and AVL-LR in the frequency of zero scores. In the receiver operating characteristic curves analysis, although the area under the curve (AUC) of AVL-SR and AVL-LR for diagnosing aMCI was significantly different, the cut-off scores of the two indicators were identical. In the subgroup of ages 80 to 89, the AUC of the two indicators showed no significant difference. Therefore, we concluded that AVL-SR could substitute for AVL-LR in identifying aMCI, especially for the oldest patients.
To evaluate a simple three step procedure to identify people in the general population who are in the preclinical phase of Alzheimer's disease and dementia.
Three year population based cohort study.
Kungsholmen cohort, Stockholm, Sweden.
1435 people aged 75-95 years without dementia.
Single question asking about memory complaints, assessment by mini-mental state examination, and neuropsychological testing.
Main outcome measure
Alzheimer's disease and dementia at three year follow up.
None of the three instruments was sufficiently predictive of Alzheimer's disease and dementia when administered separately. After participants had been screened for memory complaints and global cognitive impairment, specific tests of word recall and verbal fluency had positive predictive values for dementia of 85-100% (95% confidence intervals range from 62% to 100%). However, only 18% of future dementia cases were identified in the preclinical phase by this three step procedure. Memory complaints were the most sensitive indicator of Alzheimer's disease and dementia in the whole population, but only half the future dementia cases reported memory problems three years before diagnosis.
This three step procedure, which simulates what might occur in clinical practice, has a high positive predictive value for dementia, although only a small number of future cases can be identified.
What is already known on this topicAlzheimer's disease is characterised by a preclinical phase, during which cognitive deficits are seen before diagnosisElderly people with subjective memory complaints and objective global cognitive impairment have a high risk of developing Alzheimer's disease and dementiaWhat this study addsThis three step procedure (self report of memory complaints, test of global cognitive functioning, and then domain specific cognitive tests) has a positive predictivity of 85-100% for Alzheimer's disease and dementia at three yearsHowever, only 18% of people in the preclinical phase can be identified using this procedureAbout half of the people in the preclinical phase of Alzheimer's disease and dementia do not report problems with their memory three years before diagnosis
Deep brain stimulation (DBS) surgery, an effective treatment for medication-refractory Parkinson’s disease (PD), may also lead to selective cognitive declines. In this continuation of a report by Zahodne et al. (2009), we compare cognitive performance of 24 PD patients who underwent unilateral implantation of the globus pallidus internal segment (GPi) or subthalamic nucleus (STN) to that of 19 PD controls. We used group statistical comparisons as well as Reliable Change Indexes (RCIs) to examine performance on measures of memory, processing speed, executive function, and visuospatial perception at baseline and 16 months after surgery. Significant between-group differences were noted on a psychomotor processing speed task. However, a significantly higher proportion of DBS patients than controls demonstrated reliable individual decline on a word list recall task (HVLT-R) and on several processing speed tests. Reliable improvements were noted on tests of visuospatial functioning. There was variability in individual outcome on executive functioning tests, with a small proportion of DBS patients demonstrating reliable decline and some demonstrating reliable improvement. Use of Reliable Change highlights the occurrence of individual variability, revealing declines and improvements in a small proportion of unilateral DBS patients that were not evident upon group comparison. These findings must be interpreted in light of group-level differences between the PD control and DBS patients on demographic and disease-related factors.
Parkinson’s disease; Deep brain stimulation; Reliable Change
A blood-based biomarker of Alzheimer’s disease (AD) progression could be instrumental in targeting asymptomatic individuals for treatment early in the disease process. Given the direct connection between sphingomyelins (SM), ceramides, and apoptosis, these lipids may be indicators of neurodegeneration and AD progression. Baseline serum SM and ceramides from 100 women enrolled in a longitudinal population-based study were examined as predictors of cognitive impairment. Participants were followed up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to cross-sectional and incident impairment (<1.5 SD below standard norms) on HVLT-immediate and -delayed memory recall and Trails A and B. SM and ceramides varied in relation to the timing of HVLT-delayed impairment: low levels were associated with cross-sectional impairment; high levels predicted incident impairment in asymptomatic individuals. Lipids were not associated with loss-to-follow-up. Results suggest serum SM and ceramides vary according to the timing of the onset of memory impairment and may be good pre-clinical predictors, or biomarkers, of memory impairment: a deficit observed early in AD pathogenesis.
Sphingomyelins; Ceramides; Serum lipid markers; Memory; Alzheimer’s disease; Biomarker