Abstract

Gender differences in visuospatial cognition favoring men are larger in tasks requiring active information manipulation than in tasks requiring passive storage. This study was designed to determine whether male advantage in active manipulation of visuospatial information can still be evidenced in Alzheimer's disease (AD). Twenty male and 20 female AD patients with equivalent age, education, dementia severity (Mini-Mental State Examination and Mattis Dementia Rating Scale), and visual discrimination abilities were recruited. We administered the forward span of Corsi block-tapping task and Vecchi's matrix memory task involving passive temporary retention of stimuli location. Active manipulation of visuospatial information was assessed with the backward span of Corsi block-tapping task and Vecchi's pathway task in which patients were required to mentally generate a pathway within a matrix. The results showed that scores on the tasks involving passive storage of visuospatial information were equivalent between the two groups of patients, whereas men performed significantly better than women in tasks requiring active manipulation of visuospatial information. This result was limited to visuospatial processing since no difference between male and female patients was evidenced in the verbal short-term memory tasks, neither when the task involved passive storage nor when the task required active processing. Therefore, this study suggests that, besides other variables such as education or lifestyle factors, gender might also modulate the cognitive manifestation of AD.

Introduction

One of the most consistent finding regarding gender cognitive differences relies on tasks tapping visuospatial abilities in which men generally perform better than women (Collins & Kimura, 1997; Maccoby & Jacklin, 1974; Vecchi & Girelli, 1998a; Weiss, Kemmler, Deisenhammer, Fleischhacker, & Delazer, 2003a). This male advantage in visuospatial cognition that emerges early during childhood (Geiser, Lehmann, Corth, & Eid, 2008) remains stable in middle-aged and elderly adults (De Frias, Nilsson, & Herlitz, 2006). The role of sexual hormones has been proposed to partially explain these differences. Indeed, multiple data arising from animal models (Edinger & Frye, 2004; Frye, Park, Tanaka, Rosellini, & Svare, 2001), epidemiological studies (Moffat et al., 2002), and clinical trials (Cherrier et al., 2005; Janowsky, Oviatt, & Orwoll, 1994) have shown that androgens influence visuospatial performances. Nonetheless, the meta-analyses that evaluated gender differences in spatial cognition showed that the various components of spatial cognition were differentially influenced by gender (Linn & Petersen, 1985; Voyer, Voyer, & Bryden 1995). Indeed, whereas large gender differences favoring men were observed in tasks involving spatial rotation, the advantage of men over women in spatial perception and spatial visualization was absent or at least more limited. Thus, men exhibit the largest advantage in tasks requiring dynamic transformations of the material in visuospatial memory.

Regarding visuospatial working memory, numerous authors proposed a distinction between passive and active processing components (Cornoldi & Vecchi, 2003; Logie, 1995). Passive storage refers to the temporary retention of information related to form and location of visual stimuli, whereas active processing refers to the retention and execution of movement sequences, as well as to the ability to operate mental rotation. According to Vecchi and Girelli (1998a), whereas no difference between men and women could be evidenced in visuospatial tasks involving passive storage, men were advantaged over women in tasks involving active manipulation of mentally generated images. Gender differences in active manipulation processing could reflect the use of different strategies. For example, women tend to select less efficient verbally mediated (analytic) strategies, whereas men preferentially use a more efficient spatially mediated strategy when operating mental rotation (Heil & Jansen-Osmann, 2008).

A possible hypothesis explaining the greater performance of men on these specific tasks could be related to sexual hormone effects on hippocampal formation, a key structure in visuospatial cognition (e.g., Maguire et al., 2000). Another cortical region playing an important role in visuospatial cognition is parietal cortex. Both hippocampal and parietal regions are early and predominantly affected in Alzheimer's disease (AD) entailing massive episodic memory and visuospatial processes impairments. Such deficits in visuospatial abilities are manifest in AD patients in a large diversity of tasks measuring visual perception (Kurylo, Allan, Collins, & Baron, 2003), working memory (Grossi, Becker, Smith, & Trojano, 1993), and visuoconstructional (Gaestel, Amieva, Letenneur, Dartigues, & Fabrigoule, 2006) abilities. The distinction between passive storage and active processing has proven useful in the characterization of visuospatial performances in normal aging (Vecchi & Cornoldi, 1999; Vecchi, Richardson, & Cavallini, 2005) but also in AD (Vecchi, Saveriano, & Paciaroni, 1998b). In the latter study, whereas both components of visuospatial working memory were impaired in AD patients compared with elderly controls, active processing was proportionally more impaired than passive storage of visuospatial information.

The issue of gender differences in cognitive performances has been poorly investigated in AD. Since AD preferentially affects hippocampal formation and parietal areas, known to be critical regions in visuospatial cognition, the present study was undertaken to determine whether gender differences in visuospatial active manipulation can still be evidenced in AD patients. For this, we compared male and female AD patients' performances in different tasks measuring passive storage and active processing of visuospatial information. We used the backward span of Corsi block-tapping task (Corsi, 1972) and Vecchi's pathway task adapted to AD (Vecchi et al., 1998b) to assess visuospatial manipulation processes. On the other hand, passive storage has been assessed with the forward span of Corsi block-tapping task and Vecchi's matrix memory task (Vecchi, Monticellai, & Cornoldi, 1995). Whereas both groups are expected to have similar performances in visuospatial tasks relying on passive storage, our hypothesis is that male AD patients will outperform women in tasks requiring active manipulation of the material.

Materials and Methods

Patients

We included 20 male and 20 female patients meeting NINCDS-ADRDA criteria (McKhann et al., 1984) for probable AD. Structural magnetic resonance imaging and biological analyses were used to exclude other possible etiology. Patients were recruited from the memory clinic of the University Hospital of Bordeaux. Patients with a history of severe head injury, alcoholism, and depressive symptomatology were excluded. Characteristics of the patients are shown in Table 1. The mean age was 76.4 (SD = 5.6) for female participants and 73.7 (SD = 7.4) for male participants. All the patients scored 20 or higher in the Mini-Mental State Examination (MMSE) scale (Folstein, Folstein, & McHugh, 1975). The mean MMSE score was 22.8 (SD = 2.4) for women and 23.2 (SD = 2.4) for men.

Table 1.

Characteristics of the participants

 Men (N = 20) Women (N = 20) p-value 
Age 73.7 (7.4) 76.4 (5.6) .29* 
Education (n [%])   .82** 
 No diploma 3 (15) 2 (10)  
 Primary degree 10 (50) 12 (60)  
 Secondary degree and plus 7 (35) 6 (30)  
MMSE (score/30) 23.2 (2.4) 22.8 (2.4) .57* 
MDRS (score/144) 120.8 (9.9) 115.7 (13.2) .14* 
VGEP (score/10) 9.5 (0.9) 9.7 (0.7) .72* 
Verbal span    
 Forwarda 4.9 (1.0) 5.3 (1.1) .30* 
 Backwardb 3.6 (0.9) 3.4 (0.9) .48* 
Visuospatial span (Corsi blocks task)    
 Forwarda 4.6 (1.0) 4.3 (0.9) .34* 
 Backwardb 4.2 (0.9) 3.5 (1.1) <.05* 
Vecchi's tasks    
 Matrix memory taska (score/8) 7.5 (1.0) 7.2 (1.3) .57* 
 Mental pathway taskb (score/8) 5.7 (2.4) 2.4 (2.4) <.001* 
 Men (N = 20) Women (N = 20) p-value 
Age 73.7 (7.4) 76.4 (5.6) .29* 
Education (n [%])   .82** 
 No diploma 3 (15) 2 (10)  
 Primary degree 10 (50) 12 (60)  
 Secondary degree and plus 7 (35) 6 (30)  
MMSE (score/30) 23.2 (2.4) 22.8 (2.4) .57* 
MDRS (score/144) 120.8 (9.9) 115.7 (13.2) .14* 
VGEP (score/10) 9.5 (0.9) 9.7 (0.7) .72* 
Verbal span    
 Forwarda 4.9 (1.0) 5.3 (1.1) .30* 
 Backwardb 3.6 (0.9) 3.4 (0.9) .48* 
Visuospatial span (Corsi blocks task)    
 Forwarda 4.6 (1.0) 4.3 (0.9) .34* 
 Backwardb 4.2 (0.9) 3.5 (1.1) <.05* 
Vecchi's tasks    
 Matrix memory taska (score/8) 7.5 (1.0) 7.2 (1.3) .57* 
 Mental pathway taskb (score/8) 5.7 (2.4) 2.4 (2.4) <.001* 

Notes: Data presented as mean (SD), unless otherwise indicated. MDRS = Mattis Dementia Rating Scale; VGEP = visual gnosis examination protocol.

aPassive storage processing task.

bActive manipulation processing task.

*Mann–Whitney U-test.

**Fisher's exact test.

Neuropsychological testing

Dementia severity

To have a reliable measure of global cognitive deterioration in both groups of patients, besides the MMSE scale, we administered the Mattis Dementia Rating Scale (MDRS, Mattis, 1988), a widely used scale assessing attentional, constructional, abstraction, and mnemonic abilities.

Visual discrimination subtest

To ensure patients presented no major visual processing deficiency, we administered the visual discrimination subtest of the visual gnosis examination protocol (VGEP, Agniel, Joanette, Doyon, & Duchein, 1992). Two training cards followed by 10 testing cards were shown to participants. Each card comprises a target stimulus consisting in a complex geometric figure presented on the top of the card. Subjects were requested to match the target stimulus with the relevant one presented among six possible stimuli displayed underneath. Scores corresponded to the number of correct responses.

Digit-span tasks

A digit-span task was used to assess participants' verbal short-term memory. Sequences of numbers were read aloud at the rate of one item per second, starting with short sequences of two numbers. Immediately afterward, the subjects were requested to recall the numbers in serial order for the forward span condition and in reverse order for the backward span condition. Two trials were administered for each sequence of the same length. The length of the sequence was increased if at least one of the two trials of similar length was repeated correctly. Verbal spans (forward and backward) corresponded to the longest sequence for which at least one of the two trials was correctly repeated.

Corsi block-tapping tasks

The Corsi block-tapping task (Corsi, 1972) assesses the ability to keep in memory a sequence of spatial locations over a short period of time. The task consisted in a series of small white cubes randomly arranged on a wooden board. The experimenter showed a spatial sequence tapping with the index finger at the rate of one cube per second, starting with short sequences of two blocks. Immediately afterward, the subjects were requested to reproduce the pattern of spatial sequences in serial order for the forward span condition and in reverse order for the backward span condition. Two trials were administered for each sequence of the same length. The length of the sequence was increased if at least one of the two trials of similar length was correctly repeated. Visuospatial spans (forward and backward) corresponded to the longest sequence for which at least one of the two trials was correctly repeated.

Vecchi's matrix memory task

A computerized version of the matrix memory task (Vecchi et al., 1995) was designed to measure visuospatial memory relying on passive storage (Fig. 1). The participants were placed in front of a computer screen displaying a two-dimensional matrix divided in 9 squares (3 × 3). Three black squares were displayed for 10 s, and the participants were asked to memorize the position of each stimulus within the matrix. Immediately afterward, a white background appeared for 2 s. Then, a blank matrix appeared and the participants were asked to point to the correct position of the three black squares presented previously. Participants performed first two training trials to ensure they had understood instructions. Then, the test phase comprised eight trials. The score corresponded to the number of successful trials.

Fig. 1.

Computerised versions of Vecchi's visuospatial tasks.

Fig. 1.

Computerised versions of Vecchi's visuospatial tasks.

Vecchi's pathway task

A computerized version of the mental pathway task adapted by Vecchi and colleagues (1998b) for AD patients was designed to measure visuospatial memory requiring active manipulation. The task relied on the same two-dimensional matrix as that used in the previous task. A starting point was always displayed in the square located in the bottom left corner of the matrix. The experimenter gave a series of moves (left, right, up, down) to participants who had to mentally imagine the displacement of the moving dot within the matrix. An example of sequence of moves is provided Fig. 1. After delivering the instructions regarding the dot displacement, a white background was displayed for 2 s. Then, a blank matrix appeared and the participants were asked to point to the square corresponding to the final position of the “imaginary” dot. In order to adapt the amount of processing requirement to each participant, the number of statements of direction to be remembered was adjusted according to each individual's verbal span. Participants were first administered two training trials to ensure instructions were understood. Then, the test phase comprised eight trials. The score corresponded to the number of successful trials.

Statistical analysis

Demographic data and scores on the different neuropsychological tests were compared between male and female AD patients groups using nonparametric statistical tests (Mann–Whitney U-test and Fisher's exact test).

Results

Demographic and neuropsychological variables

First, we compared male and female AD patients groups according to age, level of education, dementia severity, and visual discrimination scores (Table 1). No significant difference was evidenced between the groups for age (U = 160.5, p = .29) and level of education (Fisher's exact test, p = .82). Regarding dementia severity, the mean MMSE (U = 178.0, p = .57) and MDRS (U = 145.0, p = .14) scores were not significantly different between the female and male AD patients. For visual discrimination, the mean VGEP scores of female and male AD patients were not significantly different (U = 186.5, p = .72).

Verbal short-term memory measures

We compared verbal short-term memory spans between the two groups of patients. Mean forward and backward verbal span of men and women are reported Table 1. No differences were found between the groups neither in the forward verbal span task (U = 161.0, p = .30) nor in the backward span task (U = 173.0, p = .48).

Passive storage and active manipulation of visuospatial information

Finally, we compared visuospatial performances between the male and female AD patients in the two tasks involving passive storage, that is, forward span of Corsi block-tapping and Vecchi's matrix memory tasks, and in the two tasks involving active manipulation, that is, backward span of Corsi block-tapping and Vecchi's mental pathway tasks. Mean performances of the groups are reported in Table 1. Regarding passive storage, no differences were found between the groups for forward Corsi blocks task (U = 164.0, p = .34) and for Vecchi's matrix memory task (U = 178.0, p = .57). In contrast, the statistical analyses showed significant differences in the two tasks involving active manipulation. The female patients performed significantly lower than male patients in the backward Corsi blocks task (U = 127.0, p < .05) as well as in Vecchi's pathway task (U = 69.5, p < .001).

Discussion

Previous results have shown that AD patients were more impaired in visuospatial tasks requiring active processing than in those involving passive storage (Vecchi et al., 1998b). Since men are assumed to be advantaged in visuospatial tasks requiring active processing, this study was undertaken to determine whether gender influence on visuospatial performances persists in patients who have developed AD. Our results showed that male AD patients performed significantly better than women in tasks requiring active visuospatial manipulation. On the contrary, the two groups of patients exhibited equivalent performances in the more passive visuospatial memory tasks. Therefore, gender differences in visuospatial processing in AD evidenced in our study were limited to the tasks yielding dynamic transformation of the material. Importantly, the lower performances of female participants could not be related to a difference in dementia severity or a difference in basic visual identification abilities. Indeed, dementia severity assessed by both MMSE and MDRS as well as the visual discrimination abilities were similar between the two groups of male and female AD patients. An interesting finding is that the two groups exhibited equivalent performances in the backward verbal span task. Thus, the advantage of male over female AD patients in active manipulation processing may not be generalizable to all tasks modalities but would rather be limited to visuospatial information processing. Our study gives support to the assumption that despite AD, men still present a greater ability than women to operate manipulation on visuospatial information and to use this dynamically changing information to guide their performance.

The tasks selected to assess passive storage were the forward span of Corsi blocks task and Vecchi's matrix memory task, whereas the tasks selected to assess active manipulation were the backward span of Corsi blocks task and Vecchi's pathway task. Regarding the forward span of the Corsi blocks task, despite its spatio-sequential component (Della Sala, Gray, Baddeley, Allamano, & Wilson, 1999), it is generally considered as a more passive task than the backward span task (Vecchi & Cornoldi, 1999). Vecchi's matrix memory task is also assumed to yield passive storage of visuospatial information because the location of the target squares has to be remembered in the same configuration as that presented previously. The only two tasks yielding significant differences between men and women were the tasks involving active processing in visuospatial working memory. Since attentional resources are being increased with the necessity to reproduce the sequences in reverse order in the Corsi block-tapping task (Vandierendonck, Kemps, Fastame, & Szmalec, 2004), the backward span task is assumed to require a higher degree of active manipulation than the forward tapping condition. In the same vein, Vecchi's pathway task has been chosen to assess active manipulation processes since generating the mental image of a dot displacing through a pathway requires participants to continuously create new images. A possible limitation is that some subjects could have used a verbal strategy to accurately execute the task. In particular, when the processing requirement is substantially increased, a strategy could consist in recoding the pattern of displacements into a verbal format. However, even though the existence of verbal strategies could not be totally excluded, Vecchi and Girelli (1998a) have shown that the role of such strategies in executing the pathways is limited.

Different hypotheses can be advanced to explain gender-related performances in visuospatial tasks. First, male advantage in tasks requiring maintenance and manipulation of visuospatial information could reflect the use of different cognitive strategies in men and women. Gender differences in the generation of mental pathways could be related to men' greater propensity to conceive the overall shape of the pathway, whereas women may preferentially use analytic part-by-part strategies. In a mental rotation task, Heil and Jansen-Osmann (2008) showed that men did not increase the time to perform the task with the increasing complexity of figures suggesting that they preferentially rely on holistic spatially oriented strategy allowing them rotating the figure as a whole in a unitary process. On the contrary, in women, the time to operate mental rotation increased with figures complexity suggesting that they preferentially relied on a verbally mediated analytic strategy in which the figure is parsed into individual pieces rotated separately. In neuroimaging studies, this gender-related strategic differentiation has been proposed to explain the results showing that men exhibit greater parietal areas activation, whereas women exhibit lower activation of the parietal lobe but additional activation of the frontal lobe while performing a mental rotation task (Schöning et al., 2007; Thomsen et al., 2000; Weiss et al., 2003b). Another hypothesis explaining gender effects on visuospatial performances relies on the relationship between androgens and visuospatial memory. Indeed, studies with animal models have shown that spatial memory is impaired after gonadectomy (Frye et al., 2001) and that it is restored with androgen adjunction (Edinger & Frye, 2004). Epidemiological studies also showed that lower testosterone levels in elderly men were associated with worse spatial memory (Moffat et al., 2002). On the other hand, testosterone adjunction increases spatial cognition in elderly men (Janowsky et al., 1994), female-to-male transsexuals (Van Goozen, Cohen-Kettenis, Gooren, Frijda, & Van de Poll, 1994), and hypogonadal men (Gray et al., 2005).

Whether gender influences visuospatial deficits in AD may be interesting to consider in the context of the “cognitive reserve” hypothesis (Stern, 2006, for a review). Besides lifestyle factors, such as education, occupational attainment (e.g., Stern et al., 1994), or stimulating leisure activities (e.g., Scarmeas, Levy, Tang, Manly, & Stern, 2001), sex was also shown to modulate the probability of developing AD, with women having higher risk than men (e.g., Letenneur et al., 1999). In addition to distinct probabilities of incidence, the clinical manifestation of the disease may not be exactly the same in men in women, since as may be seen in the present study, at equivalent level of dementia severity, male and female AD patients exhibit different level of performances in specific dimensions of cognitive functioning. Therefore, despite the physiopathological process of AD irremediably affecting hippocampal and parietal regions, sex may contribute to the constitution of individual cognitive reserve capacity likely to modulate the clinical exteriorization of the disease.

Conflict of Interest

None declared.

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