Abstract

The decline of verbal memory and learning is one of the main symptoms of Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). The aim of this study was to examine the effectiveness of the Hopkins Verbal Test-Revised (HVLT-R) to discriminate subjects with AD, amnestic MCI (aMCI), and a healthy control group in a Spanish population. Two hundred ninety-eight subjects were assessed with the HVLT-R and the Spanish version of the Mini-Mental State Examination (MEC 35). There were significant differences in the HVLT-R delay recall and total free recall scores of aMCI, AD, and control subjects. Cut points with satisfactory sensitivity and specificity were found and showed better sensitivity than the MEC 35 in detecting AD and aMCI. Recognition scores failed to differentiate between impaired and control subjects. The HVLT-R delay recall and total free recall scores present high diagnostic utility for their employment in clinical practice in AD and MCI in a Spanish population.

Introduction

Memory impairment is one of the most common cognitive deficits in Mild Cognitive Impairment (MCI) (Brooks & Loewenstein, 2010; Greenaway et al., 2006; Price et al., 2010) and dementias (Cherbuin, Sachdev, & Anstey, 2010; Cottingham & Hawkins, 2010; Filoteo et al., 2009; Kuslansky et al., 2004) and is frequently the first symptom of Alzheimer's disease (AD) (Brooks & Loewenstein, 2010; Rabin et al., 2009).

MCI is also thought to be a prodromal phase of dementia (Arnaiz & Almkvist, 2003; Cherbuin et al., 2010; Greenaway et al., 2006; Lonie et al., 2010; Petersen, 2009; Petersen & Negash, 2008) and therefore highly predictive of subsequent conversion (Busse, Angermeyer, & Riedel-Heller, 2006; Dickerson, Sperling, Hyman, Albert, & Blacker, 2007).

The decline in verbal memory has received considerable attention in the literature over the past few years as the main symptom of both AD and MCI (Brooks & Loewenstein, 2010; Price et al., 2010). MCI patients experience memory loss that differs significantly from normal age cognitive decline, but these individuals preserve the overall cognitive functions and activities of daily living (ADLs) and thus do not meet the criteria for dementia (Petersen & Bennett, 2005; Petersen et al., 2001). Studies indicate that amnestic MCI (aMCI) and AD subjects display a pattern of deficits, characterized by reduced learning (Loewenstein et al., 2004), faster rate of forgetting (Greenaway et al., 2006; Vanderploe, Yuspeh, & Schinka, 2001), and a decline in delay recall (Schmand, Huizenga, & van Gool, 2010). Deficits in delay recall and other memory functions have also evidenced a predictive value in the progression of MCI to dementia (Jak et al., 2009; Rabin et al., 2009). Consequently, the use of valid assessment tools is essential for detecting very early cognitive impairment and AD and for guiding useful interventions (Brooks & Loewenstein, 2010).

Not only do cognitive tests need to detect early stages of dementia or cognitive impairment, they also need to be quick and easy to administer (Stein, Luppa, Brahler, Konig, & Riedel-Heller, 2010). Although global measures of cognition such as the Mini-Mental State Examination (MMSE) have these advantages and have been validated in Spanish populations, they frequently present low sensitivity for producing an accurate diagnosis (Jacova, Kertesz, Blair, Fisk, & Feldman, 2007). These instruments have shown a floor effect in patients with advanced dementia, subjects with low levels of education, or subjects whose native language is not English (Schultz-Larsen, Lomholt, & Kreiner, 2007), as well as a ceiling effect in subjects with a high level of education (O'Bryant et al., 2008) and subjects with MCI (de Jager, Schrijnemaekers, Honey, & Budge, 2009).

Moreover, in spite of the large number of Spanish speakers in the world, the availability of complete instruments to valuate cognitive functions in these populations remains insufficient and these instruments are even more limited for the assessment of verbal memory and learning. In these populations, usually complete batteries are employed that include memory tests such as the Neuropsi Battery of Tests (Ostrosky-Solis, Ardila, & Rosselli, 1999). However, the time required to administer them and the absence of parallel forms for the detection of changes over time has limited their use. All these variables make it difficult to identify appropriate verbal memory instruments for a correct diagnosis of cognitive faculties in Spanish-speaking subjects.

The Hopkins Verbal Test-Revised (HVLT-R; Brandt & Benedict, 2001) was created, considering the need for useful scales for detecting memory impairment, based on more extensive verbal memory tests like the California Verbal Learning Test (Frank & Byrne, 2000). The six equivalent forms of the HVLT-R available make retesting possible even at short intervals. This is especially useful when the assessment needs to be repeated, such as in patients with progressive disorders or dementias (Gonzalez Palau, 2012).

Moreover, the HVLT-R has proved to be very useful for the effective assessment of healthy elderly population (Schrijnemaekers, de Jager, Hogervorst, & Budge, 2006), MCI (Lonie et al., 2010), and dementia (Foster et al., 2009; Frank & Byrne, 2000; Hogervorst et al., 2002; Kuslansky et al., 2004) but to our knowledge no study has been undertaken on a Spanish population.

The aim of this study was to make a preliminary analysis of the clinical utility of the HVLT-R in an older population, measuring the test's capacity to satisfactorily discriminate between older Spanish patients who have MCI or AD and healthy elderly control subjects.

Materials and Methods

Participants

Two hundred ninety-eight elderly people recruited from eight residential facilities, two community centers, and one memory clinic participated in the study. The centers were located in five different cities in Spain. All current subjects who were older than 60 years and fluent in Spanish were invited to take part. Older adults with severe depression or other relevant psychiatric or neurological diagnosis, unstable medication, or severe hearing problems that make it impossible to complete the tests were excluded from the study.

Fifty-four participants had been diagnosed with AD, 132 with an aMCI single or multiple domain, and 109 participants did not present any cognitive impairment. All diagnoses were made by a psychiatrist according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for dementia of the Alzheimer type and Petersen's criteria for aMCI (Petersen et al., 1999). Subjects were diagnosed as having aMCI if they scored <1.5 SD from the norm on one memory test, did not have dementia, and were still functioning independently (Petersen et al., 1999). A diagnosis of an aMCI single domain was assumed if the impairment involves only memory, whereas an aMCI multiple domain was assumed with impairments in the memory plus at least one other cognitive domain.

Information for these diagnoses was obtained in structured interviews with participants and with members of the family on demographic variables, on personal and family medical history, as well as on social, behavioral, and occupational history. Participants also received a battery of cognitive tests that included the Wechsler Memory Scale III (Wechsler, 2004), the Color Trail Tests 1 and 2 (D'Elia, Satz, Uchiyama, & White, 1996), the Clock Drawing Test (Cacho, Garcia-Garcia, Arcaya, Vicente, & Lantada, 1999), the Instrumental ADL Scale (Lawton & Brody, 1969), and the Geriatric Depression Scale (GDS) (Yesavage et al., 1982). After the first interview, each subject was asked to return for a brief second day of testing, where they received the HVLT-R and the MEC 35 (Lobo, Esquerra, Gomez Burgada, Sala, & Seva, 1979), a Spanish version of the MMSE. These raters were blinded to the participants' cognitive status and different from those who had made the diagnoses. The examiners who made the diagnoses were not informed of the HVLT-R and MEC 35 results.

Instrument

The HVLT-R measures memory in addition to the rate of verbal learning over three successive learning and recall trials. A 12-item list of words is presented orally at a rate of one word every 2 s, and the participant recalls as many words as possible in any order immediately after the presentation. Each list consists of three semantic categories with four words in each category. Three successive presentations and recall tests are administered. After the third learning trial, the participant is instructed to remember the words. After a 20-min delay, the participant again recalls the words in any order. The delay free recall is followed by a 24-word recognition trial. Twelve are the target list words, 6 are the categorically related non-target words and 6 are the unrelated non-target words.

Procedure

The original HVLT-R was translated into Spanish following the use of back translation methods. The procedure was performed as follows: (a) the original instrument was translated by three clinical psychologists, one bilingual, and two with an excellent command of English; (b) the HVLT-R materials and translations were handed to six specialists in neuropsychology, six clinical psychologists, and one psychiatrist for their revision; (c) the remarks of translations and professionals' were redistributed among the members of the same team for a second revision and discussion of the material; (d) back translations were made from Spanish into English by a bilingual psychologist; and (e) a final revision was made by clinical neuropsychology and psychiatry professionals.

Assessment

All the assessments were conducted at the memory clinic or community centers, where the participants habitually went, or the institutions (residential facilities), where the individuals lived. For each subject, scores were recorded relating to performance in each of the three free recall trials (HVLT-R I, II, and III), total recall over the same three trials, the delay recall trial, and HVLT-R recognition. One hundred seventy-four participants were assessed using only the HVLT-R form 1, and 124 participants were assessed twice using the HVLT-R forms 4 and 1 randomly, with an interval of 3 months.

Data Analysis

The various groups were compared with regard to demographic variables using analysis of variance (ANOVA) and χ2 for ordinal/categorical data. ANOVA and t-test for independent samples were used to compare the HVLT-R main mean scores between AD, aMCI, and healthy subjects. Non-normally distributed variables were compared using the Mann–Whitney U-test. Backward regression analyses were carried out to establish the best predictive factors for the performance of HVLT-R main scores and MEC 35. Receiver operating characteristic analysis was used to examine the various sensitivity–specificity trade-offs of the HVLT-R free recall and delay recall scores for detecting AD and aMCI. A direct comparison was made between these scores and the MEC 35 in identifying the patients with AD and aMCI. The χ2 test was used to detect the optimum cut points for the HVLT-R and MEC 35. The Positive Predictive Value and the Negative Predictive Value were also calculated. Finally, the equivalence of forms 1 and 4 was assessed using t-test for related samples.

Results

Socio Demographic Characteristics of the Sample

Demographic characteristics of the complete sample and split by the type of the group are given in Table 1. The overall sample had more women (74.8%) and had a mean age of 82.23 (±7.8). The sample was Spanish (100%) with a mean education of 8.3 years. There were no significant differences between the three groups of subjects in gender, χ2 = 2.94, df = 2, p = .230; years of education, F(2,243) = 1.326, p = .267; age, F(2,284) = 0.810, p = .446; and depression scores, F(2,293) = 1.778, p = .171.

Table 1.

Demographic characteristics of the complete sample and split by clinical diagnosis

Characteristics All (n = 298) Control (n = 109) MCI (n = 132) AD (n = 54) p-value 
Age (M ± SD82.23 ± 7.8 81.87 ± 6.84 81.97 ± 9.16 83.44 ± 5.67 .267 
Education (M ± SD8.30 ± 3.35 8.15 ± 3.16 8.87 ± 3.25 7.75 ± 3.87 .446 
Gender (%) 
 Women 74.8 73.2 81.4 66.1 .230 
 Men 25.2 25.8 18.6 33.9  
Nationality: % Spanish 100 100 100 100 — 
HVLT-R free recall (M ± SD13.43 ± 5.16 17.67 ± 4.59 11.66 ±3.98 9.63 ± 2.5 <.0001 
HVLT-R delay recall (M ± SD3.00 ± 2.76 5.61 ± 2.22 1.79 ± 1.94 1.06 ± 1.42 <.0001 
HVLT-R recognition (M ± SD8.60 ± 3.38 9.81 ± 2.88 7.90 ± 3.24 7.90 ± 4.01 <.0001 
Geriatric Depression Scale (M ± SD3.69 ± 3.09 3.34 ± 3.07 3.98 ± 3.33 3.61 ± 2.67 .173 
MEC 35 (M ± SD24.38 ± 4.15 26.74 ± 2.88 23.8 ± 3.76 20.67 ± 4.33 <.0001 
Characteristics All (n = 298) Control (n = 109) MCI (n = 132) AD (n = 54) p-value 
Age (M ± SD82.23 ± 7.8 81.87 ± 6.84 81.97 ± 9.16 83.44 ± 5.67 .267 
Education (M ± SD8.30 ± 3.35 8.15 ± 3.16 8.87 ± 3.25 7.75 ± 3.87 .446 
Gender (%) 
 Women 74.8 73.2 81.4 66.1 .230 
 Men 25.2 25.8 18.6 33.9  
Nationality: % Spanish 100 100 100 100 — 
HVLT-R free recall (M ± SD13.43 ± 5.16 17.67 ± 4.59 11.66 ±3.98 9.63 ± 2.5 <.0001 
HVLT-R delay recall (M ± SD3.00 ± 2.76 5.61 ± 2.22 1.79 ± 1.94 1.06 ± 1.42 <.0001 
HVLT-R recognition (M ± SD8.60 ± 3.38 9.81 ± 2.88 7.90 ± 3.24 7.90 ± 4.01 <.0001 
Geriatric Depression Scale (M ± SD3.69 ± 3.09 3.34 ± 3.07 3.98 ± 3.33 3.61 ± 2.67 .173 
MEC 35 (M ± SD24.38 ± 4.15 26.74 ± 2.88 23.8 ± 3.76 20.67 ± 4.33 <.0001 

Notes: MEC 35 = Spanish version of the MMSE; HVLT-R = Hopkins Verbal Test-Revised; MCI = Mild Cognitive Impairment; AD = Alzheimer's Disease.

Differences Between Groups in HVLT-R Scores

Table 1 shows the main scores obtained by the three groups in the HVLT-R. As expected, the groups evidenced significant differences in total free recall scores, F(2,273) = 89.03, p < .001; delay recall scores, F(2,276) = 135.29, p < .001; and recognition scores, F(2,278) = 10.87, p < .001. The normal control subjects had significantly higher mean scores on the HVLT-R total free recall scores (t = 13.7; df = 142,91; p < .0001; 95% confidence interval [CI]: 6.883–9.20) and delay recall scores (Mann–Whitney U-test = 252.50; p < .0001) than subjects with AD. Moreover, healthy controls also scored significantly higher in total free recall (t = 10.326; df = 194,783; p < .0001; 95% CI: 4.85–7.15) and delay recall scores (Mann–Whitney U-test = 1,482; p < .0001) than the MCI group. The recognition indexes were also lower in the MCI group (t = 4,695; df = 221,76; p < .0001; 95% CI: 2.72–2.715) and in the AD (Mann–Whitney U-test = 2,287; p < .001) subjects when compared with the control group. However, the main differences were found in total free recall and delay recall scores. Fig. 1a and b shows the distribution and the means of the HVLT-R main scores in the three groups.

Fig. 1.

(a) Distribution and means of HVLT-R total free recall scores by the diagnostic group. (b) Distribution and means of HVLT-R delay recall scores by the diagnostic group.

Fig. 1.

(a) Distribution and means of HVLT-R total free recall scores by the diagnostic group. (b) Distribution and means of HVLT-R delay recall scores by the diagnostic group.

Predictive Factors for Performance on the HVLT-R

Backward regression analyses were carried out to establish the best predictive factors for performance on each of the tests, with the HVLT-R total free recall, delay recall, and recognition scores and MEC 35 as dependent variables and age, years of education, gender, and depression scores (GDS) as independent variables. In AD, age was shown to significantly influence the HVLT-R free recall scores (p = .001), delay recall scores (p = .038), and performance on the MEC 35 (p = .017). In aMCI, age and depression scores showed up as having an influence in HVLT-R free recall scores (p = .016). Age also appeared as having an influence in HVLT-R delay recall scores (p < .0001) and in MEC 35 scores (p = .001).

Mild Cognitive Impairment

Table 2 and Fig. 2a show the sensitivity and specificity of different cut points on the free recall scores and delay recall scores for discriminating the aMCI group from the control group. The total area under the curve (AUC) for the HVLT-R free recall was 0.843 (p < .0001; 95% CI: 0.782–0.886) and was 0.899 (p < .0001; 95% CI: 0.852–0.931) for the HVLT-R delay recall. The optimal cutting point for detecting aMCI in this group of subjects on the HVLT-R free recall scores was 15 (sensitivity = 0.835, specificity = 0.653) and for delay recall scores it was 4 (sensitivity = 0.881, specificity = 0.703). Fig. 2a also shows the sensitivity and the specificity of different cut points on the MEC 35 for discriminating the group with aMCI from the healthy control group. The total AUC for the MEC 35 is 0.758 (p < .0001; 95% IC: 0.711–0.834). Although the AUCs were similar for both tests, the HVLT-R delay and free recall scores had better sensitivity than the MEC 35 in detecting patients with aMCI. We also examined the HVLT-R recognition scores for discriminating aMCI. The AUC is 0.681 (p < .0001; 95% CI: 0.610–0.752) and sensitivity is 0.610 when the specificity is 0.680. When sensitivity increases to 0.760, specificity decreases to 0.485. We conclude that the HVLT-R recognition score does not improve identification of aMCI above the free recall or delay recall scores from the HVLT-R in our sample.

Table 2.

Sensitivity and specificity of HVLT-R free recall and delay recall scores and MEC 35 at different cut points for detecting MCI with corresponding Positive Predictive Value and Negative Predictive Value

 Score Sensitivity Specificity PPV NPV 
HVLT-R free recall ≤14 0.701 0.737 0.774 0.658 
≤15 0.835 0.653 0.746 0.750 
≤16 0.898 0.585 0.699 0.841 
HVLT-R delay recall ≤3 0.754 0.808 0.833 0.721 
≤4 0.881 0.703 0.776 0.817 
≤5 0.952 0.534 0.706 0.891 
MEC 35 ≤25 0.685 0.760 0.784 0.655 
≤26 0.764 0.685 0.735 0.684 
≤27 0.850 0.470 0.671 0.712 
 Score Sensitivity Specificity PPV NPV 
HVLT-R free recall ≤14 0.701 0.737 0.774 0.658 
≤15 0.835 0.653 0.746 0.750 
≤16 0.898 0.585 0.699 0.841 
HVLT-R delay recall ≤3 0.754 0.808 0.833 0.721 
≤4 0.881 0.703 0.776 0.817 
≤5 0.952 0.534 0.706 0.891 
MEC 35 ≤25 0.685 0.760 0.784 0.655 
≤26 0.764 0.685 0.735 0.684 
≤27 0.850 0.470 0.671 0.712 

Notes: MEC 35 = Spanish version of the MMSE; HVLT-R = Hopkins Verbal Test-Revised; PPV = Positive Predictive Value; NPV = Negative Predictive Value.

Fig. 2.

Receiver operating characteristic curves for MEC 35. HVLT-R free recall and delay recall scores in the detection of (a) MCI and (b) AD.

Fig. 2.

Receiver operating characteristic curves for MEC 35. HVLT-R free recall and delay recall scores in the detection of (a) MCI and (b) AD.

Alzheimer's Desease

Table 3 and Fig. 2b show the sensitivity and the specificity of different cut points on the total free recall scores and delay recall scores from the HVLT-R and the MEC 35 for discriminating subjects with AD from healthy controls. The total AUC for the HVLT-R for total free recall scores is 0.949 (p < .0001; 95% CI: 0.917–0.981) and for delay recall scores is 0.948 (p < .0001; 95% CI: 0.914–0.981). At a cut point of <13, the HVLT-R total free recall score has a sensitivity of 0.958 and specificity of 0.848. In delay recall scores, the optimal cut point is 3 (sensitivity = 0.885 and specificity = 0.808). Fig. 2b also shows the sensitivity and the specificity of different cut points on the MEC 35 for discriminating those with AD from healthy controls. The total AUC for the MEC 35 is 0.876. These findings indicate that both the HVLT-R and the MMSE were able to discriminate between older patients who have mild AD and those who do not have AD. However, the HVLT-R had better sensitivity than the MEC 35 in detecting patients with mild AD.

Table 3.

Sensitivity and specificity of HVLT-R free recall and delay recall scores and MEC 35 at different cut points for detecting AD with corresponding Positive Predictive Value and Negative Predictive Value

 Score Sensitivity Specificity PPV NPV 
HVLT-R free recall ≤11 0.792 0.919 0.809 0.900 
≤12 0.854 0.879 0.774 0.926 
≤13 0.958 0.848 0.754 0.977 
HVLT-R delay recall ≤2 0.830 0.928 0.846 0.920 
≤3 0.885 0.808 0.708 0.930 
≤4 0.901 0.677 0.614 0.985 
MEC 35 ≤23 0.725 0.870 0.740 0.861 
≤24 0.784 0.830 0.702 0.843 
≤25 0.922 0.650 0.573 0.942 
 Score Sensitivity Specificity PPV NPV 
HVLT-R free recall ≤11 0.792 0.919 0.809 0.900 
≤12 0.854 0.879 0.774 0.926 
≤13 0.958 0.848 0.754 0.977 
HVLT-R delay recall ≤2 0.830 0.928 0.846 0.920 
≤3 0.885 0.808 0.708 0.930 
≤4 0.901 0.677 0.614 0.985 
MEC 35 ≤23 0.725 0.870 0.740 0.861 
≤24 0.784 0.830 0.702 0.843 
≤25 0.922 0.650 0.573 0.942 

Notes: MEC 35 = Spanish version of the MMSE; HVLT-R = Hopkins Verbal Test-Revised; PPV = Positive Predictive Value; NPV = Negative Predictive Value.

We also examined the HVLT-R recognition scores for discriminating AD from healthy controls. The results indicated that AUC is 0.627 (p < .048; 95% CI: 0.499–0.704) and when sensitivity is 0.638 the specificity is 0.485. When sensitivity increases, specificity decreases even more. As with aMCI, we conclude that the HVLT-R recognition scores do not improve the identification of AD in our sample.

Equivalence of Forms 1 and 4

One hundred twenty-four subjects were assessed using forms 1 and 4 of the HVLT-R. One of these forms (1 or 4) was administrated first, and 3 months later, each subject was newly assessed with the other version of the test. The order was selected randomly for each subject. No significant differences were found in total free recall scores (t = 1.116; p = 0.249; 95% CI: −0.318 to 1.215) and delay recall scores (t = 0.380; p = .705; 95% CI: −0.394 to 0.581) of both forms of the HVLT-R. However, significant differences were found between recognition scores of forms 1 and 4 (t = −2.674; p = .009; 95% CI: −2.104 to −0.314). More words were recognized in form 4 (M = 8.84; SD = 3.09) of the test than form 1 (M = 7.75; SD = 3.81), indicating that both forms are equivalent in delay recall and total free recall scores but not in recognition indexes.

Discussion

The aim of this study was to make a preliminary analysis of the clinical utility of the HVLT-R for detecting MCI and AD in Spanish older adults. Validated instruments for Spanish-speaking populations are very frequently needed. This could avoid usual diagnostic errors and could improve the delivery of competent neuropsychological services as well as the reliability of research (Cherner et al., 2007).

The results of this study indicate that the HVLT-R constitutes a promising instrument for differentiating aMCI and AD patients from healthy older adults. Other studies have also reached similar results using the original version of the scale, but most of them have analyzed the utility of the HVLT-R in a population with dementia (Aretouli & Brandt, 2010; Frank & Byrne, 2000; Hogervorst et al., 2002; Kuslansky et al., 2004). In contrast, this study deliberately included mild dementia as well as mild cognitive impaired subjects in response to the common clinical challenge of distinguishing MCI from healthy aging (Gonzalez Palau, 2012; Lonie, Tierney, & Ebmeier, 2009).

Also, a previous study provided by Cherner and colleagues (2007) analyzed the use of the HVLT-R in Spanish-speaking populations with promising results, but they included a healthy sample with an upper age of 55. As expected, this study found that the existing norms of the HVLT-R were particularly inadequate for Spanish-speaking populations, where up to two thirds of the participants with 6 or fewer years of education fell within the impaired range.

In our study, there were no differences between control and aMCI and AD groups in the sociodemographic characteristics of the participants (age, sex, or years of education), which facilitated the comparison between the groups. The results revealed significant differences between impaired groups (aMCI and AD) and healthy control participants in total free recall scores and delay recall scores of the test. These main HVLT-R scores were able to separate older persons with mild AD or aMCI from healthy subjects.

In AD (Foster et al., 2009; Hogervorst et al., 2002; Kuslansky et al., 2004; Schrijnemaekers et al., 2006) and MCI (de Jager et al., 2009), other studies had shown that the HVLT-R could predict the cognitive functions of older adults with better sensitivity than other screening tests, such as the MMSE. The use of the traditional MMSE cutting point 23/24 for a diagnosis of AD in the clinical sample that we studied led to considerably lower sensitivity (0.784) as well as lower specificity (0.830) than those found in HVLT-R. The optimal cutting point for detecting AD in this group of subjects on the HVLT-R total free recall score was <13 and presents a sensitivity of 0.958 and a specificity of 0.848. In delay recall scores, the optimal cut point was 3 (sensitivity = 0.885, specificity = 0.808). Moreover, in aMCI, the optimal cut point in total free recall scores was <15 (sensitivity = 0.835, specificity = 0.653) and in delay recall score was <4 (sensitivity = 0.881, specificity = 0.703).

Delay recall and recognition cut points between AD and aMCI in the HVLT-R did not show any considerable difference. This was expected since the impairment of verbal memory constitutes the main symptom in aMCI and a main area of decline in AD (Brooks & Loewenstein, 2010; Frank & Byrne, 2000; Rabin et al., 2009). The diagnosis of MCI is actually made considering the preservation or not of ADLs which are impaired in AD and not in MCI (Petersen, 2011). Although aMCI subjects recalled a greater number of words on the total free trail, the possibility of using this score in the differentiation of both diseases needs further analysis. Memory assessment still needs to be complemented by an evaluation of functional status in order to determine the magnitude of the subjects' impairment.

Moreover, recognition scores from the HVLT-R showed very low sensitivity and specificity to be able to differentiate between normal subjects and either aMCI or AD. Forms 1 and 4 also failed to demonstrate their equivalence in the recognition scores. These same results were found in the original validation of the test. In the first studies conducted on the HVLT-R, the six forms were equivalent for the recall trials but not for the recognition trials, which led the original forms to fall into two main homogeneous groups (Brandt & Benedict, 2001).

Considering that the total free recall scores and delayed recall results have proved to be indicators of impairment in AD and MCI, the findings of this study suggest that these two main scores can be used to discriminate AD and aMCI from healthy elderly subjects in a Spanish population. Recognition scores need a more in-depth study that will make it possible to reach improved sensitivity in identifying cognitive impairment. Also, the validation of the other HVLT-R forms is required for use in repeated examinations.

This study has raised a number of possibilities for future research. The preliminary results indicate the need for, and utility of, normative data from larger samples. In addition, scores on both the HVLT-R and the MMSE were significantly correlated with age and depression influenced free recall scores in aMCI. This evidenced the need for cut points that take age into consideration and the importance of taking some variables, such as depression, into account in clinical practice as they may influence the diagnostic procedure.

The use of the HVLT-R in other diseases, such as Lewy body dementia, Vascular dementia, and Parkinson with dementia could be considered, given that these patients, as well as those with other pathologies, also frequently present a decline in verbal memory and in learning (Filoteo et al., 2009; Heyanka, Mackelprang, Golden, & Marke, 2010). Also needed is an evaluation of the other forms of the HVLT-R in order to have two complete and equivalent forms of the test available for use in clinical practice.

To conclude, the HVLT-R total free recall and delay recall scores would present high diagnostic utility as a screening indicator in clinical settings. The simplicity of the scale, the short time it takes to conduct, and the results obtained support the HVLT-R for use in a Spanish population and an interest in future validation and normative studies.

Funding

This work has been supported by the Iberian Research Institute of Psychoscience (IBIP) and the University of Salamanca.

Conflict of Interest

None declared.

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