ArticlePDF Available

Verbal learning on depressive pseudodementia: Accentuate impairment of free recall, moderate on learning processes, and spared short-term and recognition memory



Objective: Depressive pseudodementia (DPD) is a clinical condition characterized by depressive symptoms followed by cognitive and functional impairment characteristics of dementia. Memory complaints are one of the most related cognitive symptoms in DPD. The present study aims to assess the verbal learning profile of elderly patients with DPD. Methods: Ninety-six older adults (34 DPD and 62 controls) were assessed by neuropsychological tests including the Rey auditory-verbal learning test (RAVLT). A multivariate general linear model was used to assess group differences and controlled for demographic factors. Results: Moderate or large effects were found on all RAVLT components, except for short-term and recognition memory. Conclusion: DPD impairs verbal memory, with large effect size on free recall and moderate effect size on the learning. Short-term storage and recognition memory are useful in clinical contexts when the differential diagnosis is required.
DOI: 10.1590/0004-282X20130102
Objective: Depressive pseudodementia (DPD) is a clinical condition characterized by depressive symptoms followed by cognitive and func-
tional impairment characteristics of dementia. Memory complaints are one of the most related cognitive symptoms in DPD. The present study
aims to assess the verbal learning profile of elderly patients with DPD. Methods: Ninety-six older adults (34 DPD and 62 controls) were asses-
sed by neuropsychological tests including the Rey auditory-verbal learning test (RAVLT). A multivariate general linear model was used to assess
group differences and controlled for demographic factors. Results: Moderate or large effects were found on all RAVLT components, except for
short-term and recognition memory. Conclusion: DPD impairs verbal memory, with large effect size on free recall and moderate effect size on
the learning. Short-term storage and recognition memory are useful in clinical contexts when the differential diagnosis is required.
Key words: dementia, Alzheimer’s disease, mood disorders, unipolar, memory.
Objetivo: A pseudodemência depressiva (PDD) é uma condição clínica onde sintomas depressivos são acompanhados por comprometi-
mento cognitivo e funcional característicos da demência. Queixas de memória são um dos sintomas mais comumente relatados na PDD.
O presente estudo almeja investigar a aprendizagem verbal de pacientes idosos com PDD. Método: 96 idosos (34 PDD e 62 controles)
realizaram testes neuropsicológicos incluindo o Teste de Aprendizagem Auditivo-Verbal de Rey (RAVLT). Adotou-se um modelo linear geral
multivariado para comparação dos grupos controlando variáveis sociodemográficas. Resultados: Pacientes com PDD apresentaram défi-
cits em todo o RAVLT, com exceção no armazenamento de curto-prazo e reconhecimento, com tamanhos de efeito moderados ou altos.
Conclusão: A PDD compromete a memória verbal mais intensamente na evocação livre e de forma moderada na aprendizagem. A memória
de curto-prazo e de reconhecimento são úteis em contextos onde o diagnóstico diferencial é necessário.
Palavras-Chave: demência, doença de Alzheimer, transtornos de humor, unipolar, memória.
Verbal learning on depressive
pseudodementia: accentuate
impairment of free recall, moderate
on learning processes, and spared
short-term and recognition memory
Aprendizagem verbal na pseudodemência depressiva:
comprometimento acentuado da evocação livre, moderado nos processos
de aprendizagem e preservação da memória de curto prazo e reconhecimento
Jonas Jardim de Paula1,2, Débora Marques Miranda2, Rodrigo Nicolato3, Edgar Nunes de Moraes4,
Maria Aparecida Camargos Bicalho4, Leandro Fernandes Malloy-Diniz1,2,3
Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, Medical School, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte MG, Brazil.
1Laboratory of Neuropsychological Investigations (LIN), UFMG, Belo Horizonte MG, Brazil;
2Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, Medical School, UFMG, Belo Horizonte MG, Brazil;
3Mental Health Department, Medical School, UFMG, Belo Horizonte MG, Brazil;
4Internal Medicine Department, Medical School, UFMG, Belo Horizonte MG, Brazil.
Correspondence: Jonas Jardim de Paula; Avenida Alfredo Balena 190; 30130-100 Belo Horizonte MG - Brasil; E-mail:
Conflict of Interest: There is no conflict of interest to declare.
Received 9 October 2012; Received in final form 9 April 2013; Accepted 16 April 2013.
Depression is one of the most frequent causes of emo-
tional disturbances and cognitive impairment and course
with an important loss of quality of life1. Depressive symptoms
are usually more frequent in elderly subjects than in younger
adults but also more dicult to detect1. Depressive symp-
toms are associated with cognitive decits, especially in
Jonas Jardim de Paula et al. Depressive pseudodementia: memory 597
of cognitive impairment (such as mild cognitive impairment
due to neurodegenerative conditions, vascular cognitive
impairment, and dementia). e diagnosis of DPD was
performed when all protocols were lled. A control group
was composed of 62 (66% women) healthy older adults also
assessed. A brief neuropsychological protocol validated for
Brazilian elders8, with the exception of the Corsi Blocks Test,
was used in all sample assessments, which includes tests of
executive functions language, constructive praxis, and work-
ing memory. e project was approved by the Local Ethical
Board (COEP-334/06), and all participants gave written con-
sent for participation.
Verbal learning assessment
The Rey auditory-verbal learning test (RAVLT)9 was
used for the memory assessment, adapted and validated
version and with appropriated normative data for Brazil-
ian elders. The test has five learning trials of a 15-word list
(A1–A5), followed by a distractor list (B1), an immediate
recall (IR), a delayed recall (DR), and a recognition trial
(Rec), representing different aspects of verbal learning.
A recent study of validity for the Brazilian elderly popu-
lation10 suggests that in normal elderly two main cogni-
tive processes are assessed by the RAVLT, one related to
information encoding and storage (comprising the first
four learning trials) and the other related to information
search and retrieving (comprising the free recalls and
recognition), with the A5 component as an intermediate
process. We used the version proposed by Malloy-Diniz
et al.9, where the words used in the learning and recogni-
tion trials were chosen based on their frequency in Brazil-
ian Portuguese.
Statistical analysis
e sociodemographic variables were compared by
independent sample t tests and χ2 tests. ese results indi-
cate dierences in age (t=2.30, p=0.024, d=0.49) and edu-
cation (t=2.10, p=0.033, d=0.45), but not gender (χ²=0.02,
p=0.880). e groups, as expected, also diered on the Short
Version of the Geriatric Depression Scale (GDS-15) score
(t=17.05, p<0.001, d=3.4). Since dierences were found on
demographic data, a multivariate general linear model was
adopted for group comparisons. e cognitive tests were
entered as dependent variables, gender and group as factors,
and age and education as covariates. Signicance levels were
established at 0.05.
Main effects for group were found on almost all the
RAVLT components, except for A1 and Rec (p>0.05) (Table
and Figure). The effect sizes were moderate for the learn-
ing components of the RAVLT (A2–A4, RAVLT-Total) and
late-onset depression2, usually associated with slow process-
ing speed, memory impairment, and executive dysfunction1-3.
e mechanism by which depression mediates the cognitive
impairment is still controversial, but certainly is multidimen-
sional and involves brain structural changes, monoaminer-
gic neurotransmission, and chronic inammatory processes
resulting in an abnormal behavior3. In some cases, the mag-
nitude of the cognitive impairment secondary to depression
may simulate the pattern expected in demented patients; a
condition referred to as depressive pseudodementia (DPD)4.
The diagnostic criteria of pseudodementia4 consist
in the presence of intellectual (cognitive) impairment
without a primary neurological or other psychiatric dis-
order other than depression that could explain the pres-
entation and presence of reversible or partially reversible
deficits. The pseudodementia diagnosis is still adopted
in mental health services, although some criticism has
been elicited5, especially on the reversibility of the cogni-
tive impairment6. Cognitive deficits in major depressive
disorder may persist after treatment, particularly those
related to episodic memory and executive functions but
may become less intense3.
Memory complaints are one of the most related cog-
nitive symptoms in clinical assessment and are neces-
sary for the diagnosis of dementia according to DSM-IV
criteria. One of the most widely used paradigms for epi-
sodic memory assessment is the auditory-verbal learn-
ing after successive presentations of a list of a certain
number of substantives. This procedure is very sensitive
for the detection of memory impairments in dementia,
mild cognitive impairment, and other neuropsychiatric
disorders7. The present study investigates the pattern of
memory impairment in pseudodementia using a verbal-
learning test.
For this study, 96 elderly were evaluated in a Reference
Center for older adults in Belo Horizonte, Brazil. e Insti-
tuto Jenny e Andrade Faria de Atenção ao Idoso is a second-
ary/tertiary public health unity of this city specialized in
health the aged population. Assessment procedures are per-
formed by a multidisciplinary sta. Diagnosis was consen-
sual by at least one geriatrician and one clinical neuropsy-
chologist. e DPD group (n=34, 23 women) was composed
of patients refereed to neuropsychology for evaluation of
cognitive performance, since they have a diagnosis of major
depressive disorder. ese referred patients have specic
impairment on cognitive screening tests but spared global
cognitive functioning and presented subjective cognitive
and functional complaints. After neuropsychological assess-
ment, results were discussed for exclusion of other causes
598 Arq Neuropsiquiatr
Table.Participants description, cognitive assessment and verbal-learning analysis.
Sociodemographic and cognitive
Participant description
Controls DPD Group Corrected model
M SD M SD F η² F η²
Age 73.94 7.84 70.21 7.1 2 – – –
Education 5.89 4.38 4.00 3.89
GDS-15 1.81 1.30 8.94 2.80
MMSE 27.34 2.96 22.85 3.62 19.98** 0 .1 9 14.95** 0.46
CDT 4.10 1.1 8 2.47 2.18 18.17** 0 .1 7 10.91** 0.39
DS 38.74 19.22 25.47 11.75 9.73* 0 .1 0 5.54** 0.24
CFT 13.15 3.78 9.79 3.27 9.81* 0 .1 0 9.93** 0.37
TT 31.63 3.22 29.47 3.36 3.45 4.76** 0.22
RAVLT-A1 4.92 1.83 4.00 1.4 4 2.69 6.40** 0.27
RAVLT-A2 7. 0 6 2.19 5.21 1.7 2 8.90* 0.09 8.70** 0.34
RAVLT-A3 8.44 2.45 6.09 2.19 8.34* 0.09 5.53** 0.24
RAVLT-A4 9.42 2.60 6.82 2.38 10.06* 0 .1 0 7.90** 0.31
RAVLT-A5 9.98 2.80 7. 0 3 2.44 10.67* 0 .1 1 8.74** 0.34
RAVLT-B1 4.06 1.64 2.82 1.64 5.04* 0.06 8.88** 0.34
RAVLT-IR 8.26 2.57 4.65 2.90 22.98** 0.21 9.48** 0.36
RAVLT-DR 8.24 2.82 4.47 2.96 27.17** 0.24 9.91** 0.37
RAVLT-Rec 8.90 4.30 7.1 3 3.13 1.38 6.85** 0.28
RAVLT–Total 38.32 11.89 29.15 9.18 7.05* 0.08 7.32** 0.30
*Significant at 0.05, **significant at 0.001.
SD: standard deviation; MED: median; DPD: depressive pseudodementia; GDS-15: short version geriatric depression scale; MMSE: mini-mental state
exam; CDT: clock drawing test; DS: digit span; CFT: category fluency test; RAVLT: Rey auditory-verbal learning test; IR: immediate recall; DR: delayed recall,
Rec: recognition.
Fig 1.Comparison of the verbal learning profile on the
Rey auditory-verbal learning test of normal controls and
depressive pseudodementia patients.
Memory impairment is a common symptom related to
depressed older adults and is usually associated with depres-
sion severity1,3. e pattern of verbal memory impairment
found in this study indicates decits on learning (moderate)
and recall (severe), with spared recognition. is pattern was
also reported by other studies using list-learning tests2,11,12.
is memory prole is expected due to the neurobiology of
depression. According to a recent review3, depression impairs
most prominently the prefrontal cortex and the mesial tem-
poral lobe regions (particularly the amygdala and the hip-
pocampus). Verbal learning is particularly associated with
an intricate circuitry involving the amygdala and its con-
nections with frontal and temporal structures, such as the
bilateral anterior cingulate cortex, bilateral medial temporal
gyrus, and the left prefrontal cortex; regions also related to
depressive symptoms13.
Posterior cortical regions are usually preserved in depres-
sion. Studies of functional neuroimage suggest that in verbal
learning tasks, such as the RAVLT, learning and recall process
are more dependent of the mesial temporal lobe and pre-
frontal cortex connections than the recognition memory14.
Aligned with this neurobiological base, the cognitive com-
ponent of familiarity from the recognition memory, usually
spared in depression, is a possible cognitive mediator for
the spared performance on the recognition trial of verbal
learning observed on the DPD group15.
large for the recall components of the test (RAVLT-IR and
-DR), according to the two-factors solution proposed on
a construct validity study of this memory task10. The DPD
group also performed below the control group on the
other cognitive measures with moderate or large effect
sizes, except for the token test.
Mean (Words)
A1 A2 A3 A4 A5 B1 IR DR Rec
RAVLT: Rey auditory-verbal learning test; DPD: depressive pseudodementia;
NC: normal controls; IR: immediate recall; DR: delayed recall; NS: nonsignifi-
cant. Effect sizes of significant (p<0.05) comparisons are reported. Error bars
indicate the standard deviation.
Arq Neuropsiquiatr 2013;71(9-A):596-599
Jonas Jardim de Paula et al. Depressive pseudodementia: memory 599
e current work has important limitations. First, although
the diagnosis of DPD was performed by multidisciplinary
consensus, the participants of this study were not followed-
up systematically. is limits the analysis of cognitive symp-
tom remission (or at least they attenuation) after depression
treatment. A second limitation is the small sample size and
the heterogeneity of the participants of the DPD group, which
may limit the generalization of the current results. However, to
our knowledge, this is the rst Brazilian work with pseudode-
mentia patients aiming specic memory process analysis in
a verbal learning paradigm. e comparison of DPD patients
with dementia and mild cognitive impairment in longitudinal
studies with larger samples is important for a better compre-
hension of the relationship of DPD and memory processes.
Our results suggest that DPD presents a moderate impair-
ment in verbal learning, a marked impairment in memory
recall but spared recognition memory. is memory prole
might be useful for clinical purposes, in contexts where the
distinction between DPD, mild dementia, mild cognitive
impairment, and normal aging is necessary.
1. Meeks TW, Vahia IV, Lavretsky H, et al. A tune in “a minor” can
“b major”: A review of epidemiology, illness course, and public
health implications of subthreshold depression in older adults.
J Affect Disord 2011:129:126-142.
2. Elderkin-Thompson V, Kumar A, Bilker WB, et al. Neuropsychological
deficits among patients with late-onset minor and major depression.
Arch Clin Neuropsychol 2003;18:529-549.
3. Beblo T, Sinnamon G, Baune BT. Specifying the neuropsychology of
affective disorders: clinical, demographic and neurobiological factors.
Neuropsychol Rev 2011;21:337-359.
4. Caine ED. Pseudodementia. Current concepts and future directions.
Arch Gen Psychiatry 1981;38:1359-1364.
5. Keren R. Will the real pseudodementia please stand up? Canadian Rev
Alzheimer’s Dis and Other Dementias 2008;11:11-14.
6. Clairfield AM. The decreasing prevalence of reversible dementias: an
updated meta-analysis. Arch Intern Med 2003;163:2219-2229.
7. Derrer DS, Howieson DB, Mueller EA, et al. Memory testing in
dementia: how much is enough? J Geriatr Psychiatry Neurol 2001;14:1.
8. de Paula JJ, Schlottfeldt CG, Moreira L, et al. Psychometric properties
of a brief neuropsychological protocol for use in geriatric populations.
Rev Psiq Clín 2010;37:246-250.
9. Malloy-Diniz LF, Lasmar VAP, Gazinelli LSR, et al. The Rey Auditory
Verbal Learning Test: applicability for the Brazilian elderly population.
Rev Bras Psiquiatr 2007;29:324-329.
10. de Paula JJ, Melo LPC, Nicolato R, et al. Reliability and construct
validity of the Rey-Auditory Verbal Learning Test in Brazilian elders.
Rev Psiq Clín 2012;39:19-23.
11. Burt DB, Zembar MJ, Niederehe G. Depression and memory
impairment: A meta-analysis of the association, its pattern, and
specificity. Psychological Bulletin 1995;117:285-305.
12. Mesholam-Gately RI, Giuliano AJ, Zillmer EA, et al. Verbal learning in
older adults with minor and major depression. Arch Clin Neuropsychol
13. Xie C, Goveas J, Wu Z, et al. Neural basis of the association between
depressive symptoms and memory deficits in nondemented
subjects: resting-state fMRI study. Human Brain Mapping 2012;33:
14. Yu SS, Johnson JD, Rugg MD. Hippocampal activity during recognition
memory co-varies with the accuracy and confidence of source
memory judgments. Hippocampus 2012;22:1429-1437.
15. Yonelinas AP. The nature of recollection and familiarity: a review of 30
years of research. J Mem Language 2002;46:441-517.
... People with feigned cognitive disorders compared to credible cognitive complainants tested using HVLT-R also showed a different pattern: worse performance in each of delayed recall, retention and recognition [37] and similar results have been found when using the related RAVLT instrument [38,39]. One study has reported RAVLT cognitive patterns in depressive pseudodementia (compared to healthy controls), which showed low scores on almost all subcomponents, with the exception of preserved recognition memory [40]. These findings suggest there are qualitatively different cognitive lapses occurring in participants with FCD, compared to those operating in early neurodegeneration, feigned symptoms, or depression. ...
Full-text available
Functional cognitive disorder (FCD) is a relatively common cause of cognitive symptoms, characterised by inconsistency between symptoms and observed or self-reported cognitive functioning. We aimed to improve the clinical characterisation of FCD, in particular its differentiation from early neurodegeneration. Two patient cohorts were recruited from a UK-based tertiary cognitive clinic, diagnosed following clinical assessment, investigation and expert multidisciplinary team review: FCD, (n = 21), and neurodegenerative Mild Cognitive Impairment (nMCI, n = 17). We separately recruited a healthy control group (n = 25). All participants completed an assessment battery including: Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test Part B (TMT-B); Depression Anxiety and Stress Scale (DASS) and Minnesota Multiphasic Personality Inventory (MMPI-2RF). In comparison to healthy controls, the FCD and nMCI groups were equally impaired on trail making, immediate recall, and recognition tasks; had equally elevated mood symptoms; showed similar aberration on a range of personality measures; and had similar difficulties on inbuilt performance validity tests. However, participants with FCD performed significantly better than nMCI on HVLT-R delayed free recall and retention (regression coefficient −10.34, p = 0.01). Mood, personality and certain cognitive abilities were similarly altered across nMCI and FCD groups. However, those with FCD displayed spared delayed recall and retention, in comparison to impaired immediate recall and recognition. This pattern, which is distinct from that seen in prodromal neurodegeneration, is a marker of internal inconsistency. Differentiating FCD from nMCI is challenging, and the identification of positive neuropsychometric features of FCD is an important contribution to this emerging area of cognitive neurology.
... How people with functional cognitive disorders perform in such tests is important to consider to understand when and how to use them in diagnosis. 13 studies examined neuropsychological test performance in people with subjective symptoms (a proportion of whom are likely to have functional disorders) in comparison with healthy, mild cognitive impairment, or dementia groups (appendix p 12): 133,155,156,168,[183][184][185][186][187][188][189][190][191][192] participants generally did similarly to or worse than healthy controls, but better than groups with mild cognitive impairment or dementia. ...
Cognitive symptoms are common, and yet many who seek help for cognitive symptoms neither have, nor go on to develop, dementia. A proportion of these people are likely to have functional cognitive disorders, a subtype of functional neurological disorders, in which cognitive symptoms are present, associated with distress or disability, but caused by functional alterations rather than degenerative brain disease or another structural lesion. In this Review, we have systematically examined the prevalence and clinical associations of functional cognitive disorders, and related phenotypes, within the wider cognitive disorder literature. Around a quarter of patients presenting to memory clinics received diagnoses that might indicate the presence of functional cognitive disorders, which were associated with affective symptoms, negative self-evaluation, negative illness perceptions, non-progressive symptom trajectories, and linguistic and behavioural differences during clinical interactions. Those with functional cognitive disorder phenotypes are at risk of iatrogenic harm because of misdiagnosis or inaccurate prediction of future decline. Further research is imperative to improve diagnosis and identify effective treatments for functional cognitive disorders, and better understanding these phenotypes will also improve the specificity of diagnoses of prodromal degenerative brain disease.
... Another clinical research also found that depressed participants, in the normal aging older adults, had a lower performance compared to non-depressed participants in cognitive domains, and the depressive symptoms may have a distinct impact on cognitive performance [29]. The studies show that the pattern of cognitive impairment associated with depressive symptoms involves executive dysfunction, reduced processing speed, and deficits in episodic memory [30][31][32], while global intellectual ability, language skills, visuospatial abilities, and semantic processing are usually spared [33]. Among them, learning and memory impairment is one of the important cognitive impairments and residual symptoms, which has a strong impact on function of patients both at home and workplace, and the life quality of patients. ...
Full-text available
Background Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in cognitive dysfunction. The disturbance of cognitive processes associated with depression, especially the impairment of learning and memory, exacerbates illness and increases recurrence of depression. XingPiJieYu (XPJY) is one of the most widely clinical formulas of traditional Chinese medicine (TCM) and can improve the symptoms of depression, including learning and memory. However, its regulatory effects haven’t been comprehensively studied so far. Recently, some animal tests have indicated that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway in hippocampus is closely related to depression and the pathogenesis of cognitive function impairments. The present study was performed to investigate the effect and mechanism of XPJY on depression and learning and memory in animal model. MaterialsThe rat model of depression was established by chronic unpredictable stress (CUS) for 21 days. The rats were randomly divided into six groups: control group, CUS group, CUS + XPJY (1.4 g/kg, 0.7 g/kg and 0.35 g/kg) groups, and CUS + sertraline (10 mg/kg) group. The sucrose preference, open field exploration and Morris water maze (MWM) were tested. The expression of cAMP, CREB, PKA and BDNF protein in hippocampus was examined with Elisa and Western Blot. The mRNA level of CREB and BDNF in hippocampus was measured with PCR. ResultsThe results demonstrated that rats subjected to CUS exhibited decreases in sucrose preference, total ambulation, percentage of central ambulation, rearing in the open field test and spatial performance in the MWM. CUS reduced the expression of cAMP, PKA, CREB and BDNF in hippocampus of model rats. These effects could be reversed by XPJY. Conclusion The results indicated that XPJY can improve depression and related learning and memory and the effect of XPJY is partly exerted through the cAMP-PKA-CREB-BDNF signaling pathway.
... We compared free recall, learning, and recognition among the groups based on recent findings by de Paula et al. 12 showing that depression patients have deficits in these measures. No differences were observed between the MDD and control groups (p 4 0.05), and both performed better than the MCI group on all of these measures. ...
Full-text available
Objective: To investigate whether the level of awareness of memory deficits is useful for discriminating between major depressive disorder (MDD) and mild cognitive impairment (MCI) in the elderly. Methods: Sixty-three consecutively referred patients (38 women and 25 men) with memory concerns comprising three groups (clinical control, MDD and MCI) underwent a memory test (Rey Auditory Verbal Learning Test [RAVLT]) and completed the Memory Assessment Complaints-Questionnaire (MAC-Q). Level of awareness was estimated by the difference between the MAC-Q score and the score on the fifth presentation of the RAVLT. Memory performance, Mini-Mental State Examination (MMSE) and depressive symptoms (Geriatric Depression Scale [GDS]) were also assessed. Results: The control (n=25), MDD (n=16), and MCI (n=22) groups were similar in age, educational level, and MMSE (p > 0.05). Among the groups, the MDD group had the most memory complaints, whereas the MCI group had the worst objective memory performance. Level of awareness was capable of discriminating between MDD and MCI (p < 0.05), but not between MDD and clinical controls (p > 0.05). MDD subjects tended to underestimate their memory functioning as compared to controls (p < 0.05). Conclusion: Level of awareness of memory deficits was significantly useful to discriminate between MCI and MDD, which is a common difficulty faced by clinicians. Future studies with larger samples are needed to confirm these findings.
... Depressive symptoms and cognitive impairment are common in older adults and often coexist in an individual patient. The pattern of cognitive impairment associated with depressive symptoms involves executive dysfunction, reduced processing speed, and deficits in episodic memory (Butters et al., 2004;Sexton et al., 2012;de Paula et al., 2013a), while global intellectual ability, language skills, visuospatial abilities, and semantic processing are usually spared (Naismith et al., 2003). Furthermore, late-life depression is a risk factor for cognitive decline and dementia, in particular Alzheimer's disease dementia (AD) and vascular dementia . ...
Full-text available
Depressive symptoms are associated with cognitive-functional impairment in normal aging older adults (NA). However, less is known about this effect on people with mild Cognitive Impairment (MCI) and mild Alzheimer’s disease dementia (AD). We investigated this relationship along with the NA-MCI-AD continuum by reanalyzing a previously published dataset. Participants (N=274) underwent comprehensive neuropsychological assessment including measures of Executive Function, Language/Semantic Memory, Episodic Memory, Visuospatial Abilities, Activities of Daily Living (ADL), and the Geriatric Depression Scale. MANOVA, logistic regression and chi-square tests were performed to assess the association between depression and cognitive-functional performance in each group. In the NA group, depressed participants had a lower performance compared to non-depressed participants in all cognitive and functional domains. However, the same pattern was not observed in the MCI group or in AD. The results suggest a progressive loss of association between depression and worse cognitive-functional performance along the NA-MCI-AD continuum.
Full-text available
Alzheimer’s disease and depressive disorder are frequent in old age. Both may be associated with depressed mood and cognitive impairment. Therefore, finding a strategy to clarify the diagnosis underlying subjective complaints of impaired cognition and depressed mood in older persons is of utmost interest. We conducted a cross-sectional retrospective observational clinical cohort study using patient records from 2014 to 2018. From 3758 patients, we included patients aged 60 years and older with a Mini-Mental-Status Examination score of 24 and above. Final analysis included all patients in whom Alzheimer’s disease biomarker analysis was performed (CSF markers of Alzheimer’s disease or PET imaging; n = 179) and patients with depressive disorder in whom Alzheimer’s disease was ruled out by analysis of biomarkers suggestive of AD (n = 70). With case-control matching for age, education and gender, performance of patients with Alzheimer’s disease was worse in acquisition, consolidation and recall of verbal information and false positive answers. None of the results, however, sufficed to differentially diagnose individual patients with Alzheimer’s disease or depressive disorder. With more severe symptoms of depression, patients with biomarker-verified Alzheimer’s disease performed worse in executive testing but were not additionally impaired in verbal episodic memory performance. We conclude that distinguishing between Alzheimer’s disease and depressive disorder is unreliable on clinical grounds and behavioral testing alone. Diagnosing the cause of subjective complaints about deteriorating cognitive function or depressed mood requires additional biomarker assessment, whereas cognitive assessment is needed to define appropriate targets of symptomatic treatment in patients with Alzheimer’s disease and depressive disorder.
Full-text available
Background: The increase in life expectancy and proportion of elderly in the population is causing an increase in dementia prevalence rates. The correct, early diagnosis of dementia is very important to clinical treatment and to improved prognosis. Therefore, it is necessary to adapt and develop assessment tools for the differential diagnosis between pathological and normal aging processes. Objective: Assess the psychometric properties and the factorial structure of a neuropsychological protocol used in geriatric assessment. Method: Subjects (n = 69) with heterogeneous cognitive complaints were assessed at the Geriatric and Gerontologic Clinic at the Clinical Hospital of the Federal University of Minas Gerais using a protocol composed of the Mini-Mental State Examination, Clock Drawing, Corsi Blocks, Verbal Fluency, Digit Span and Token Test. Statistical analyses included factorial analyses of test results, Pearson’s correlation between obtained factor, age, years of formal education and Clinical Dementia Rating (CDR) and area under the ROC curve. Results: The factorial analyses of test scores showed a general representative factor that had moderate and significant association with CDR (r = -0.672; p < 0.001) and years of formal education (r = 0.455; p < 0.001), respectively. This factor had weaker and less significant correlation with age (r = -0.282; p < 0.05). Discussion: These results point to the protocol’s good construct and criteria validity in assessing cognitive decline in the elderly. Future works concerning applicability and populational norms are needed to improve the clinical use of this assessment protocol.
Full-text available
Background: The Rey Auditory-Verbal Learning Test (RAVLT) is widely used for the assessment of episodic memory. However, there are few studies in Brazil assessing its psychometric properties. Objectives: To search for evidence of reliability and construct validity of the RAVLT, and to assess the influence of age, schooling, gender, and depressive symptoms on test performance. Methods: One hundred twenty-six healthy older adults (aged 60 and over) performed the RAVLT, Mini-Mental State Exam (MMSE), Clock Drawing Test (CDT) and the Geriatric Depression Scale. Reliability was assessed by analysis of internal consistency, and construct validity by factor analysis and correlations with the MMSE and CDT. The influence of age, schooling and depressive symptoms was estimated by conducting linear regression analysis, and the role of gender by comparing the performance of males and females. Results: The RAVLT showed a high internal consistency, weak correlations with the MMSE and CDT, and a bifactorial structure, which is related to the processes of learning and episodic memory retrieval. Only age and gender affected test performance. Discussion: Our results provide evidence of reliability and construct validity in the tested RAVLT version, attesting its potential for clinical and research purposes for the Brazilian elderly population.
Full-text available
CONTEXTO: O Teste de Aprendizagem Auditivo-Verbal de Rey (RAVLT) é amplamente utilizado para a avaliação da memória episódica. Suas propriedades psicométricas, porém, não foram bem analisadas no Brasil. OBJETIVOS: Buscar evidências de fidedignidade e validade de construto do RAVLT e analisar a influência de idade, gênero, escolaridade e sintomas depressivos no desempenho. MÉTODOS: Cento e vinte e seis idosos saudáveis realizaram o RAVLT, o Miniexame do Estado Mental (MEEM), o Desenho do Relógio (DR) e a Escala de Depressão Geriátrica. A fidedignidade foi avaliada pela análise de consistência interna e a validade de construto, pela estrutura fatorial e correlações com o MEEM e o DR. A influência da idade, escolaridade e sintomas depressivos foi estimada mediante regressão linear, enquanto diferenças de gênero foram avaliadas comparando o desempenho de homens e mulheres. RESULTADOS: O teste apresenta alta consistência interna e estrutura bifatorial relacionada aos processos de armazenamento e evocação da memória episódica. O teste mostrou, em geral, correlações fracas com o MEEM e o DR. Apenas a idade e o gênero influenciaram o desempenho na tarefa. CONCLUSÃO: Nossos resultados indicam que a versão do RAVLT analisada apresenta bons indícios de fidedignidade e validade de construto, atestando sua aplicabilidade em contextos clínicos e de pesquisa para a população estudada.
Full-text available
Late-life minor depression (miD) is a prevalent but poorly understood illness. Verbal learning and memory profiles have commonly been used to characterize neuropsychiatric disorders. This study compared the performance of 27 older adults with miD on the California Verbal Learning Test (CVLT) with 26 age-matched individuals with Major Depressive Disorder (MDD) and 36 non-depressed controls. Results revealed that the miD group performed comparably with controls and significantly better than the MDD group on several CVLT indices. Moreover, cluster analysis revealed three distinct groups, consistent with theoretical representations of "normal," "subcortical," and "cortical" verbal learning and memory profiles. The majority of the miD group showed "normal" profiles (74%), whereas most individuals with MDD displayed "subcortical" profiles (54%). The findings suggest that depression in the elderly is a heterogeneous entity and that the CVLT may be a useful tool for characterizing learning and memory in late-onset depressive disorders.
Full-text available
Neuropsychological research in patients with affective disorders shows heterogeneous results with regard to the severity and profile of cognitive impairments. In this paper we hypothesize that the investigation of clinical (subtypes, comorbidity, traumatization, personality, severity, diurnal swings, course, duration, age of onset, biased processing, rumination, motivation, experience of failure, sleep, suicidal tendencies, computer attitudes), demographic (age, education, gender) and neurobiological factors (structural and functional brain changes, glucocorticoids, medication, ECT) that are related to cognitive performance has specified the understanding of severity and profile of neuropsychological impairments. We reviewed the literature pertaining to clinical, demographic and neurobiological factors following Pubmed and PsychInfo databases using different combinations of general key-terms including "Affective Disorder," "Depression," "Mania," "Neuropsychological," "Neurobiological," "Moderator," and "Review" as well as more specific demographic, clinical and neurobiological search terms. Findings from the literature show that the consideration of these factors has improved knowledge about the severity of neuropsychological impairments in patients with affective disorders whereas the neuropsychological profile is still poorly understood. Despite limited understanding, however, the existent results provide promising suggestions for the development of treatment programs.
To account for dissociations observed in recognition memory tests, several dual-process models have been proposed that assume that recognition judgments can be based on the recollection of details about previous events or on the assessment of stimulus familiarity. In the current article, these models are examined, along with the methods that have been developed to measure recollection and familiarity. The relevant empirical literature from behavioral, neuropsychological, and neuroimaging studies is then reviewed in order to assess model predictions. Results from a variety of measurement methods, including task-dissociation and process-estimation methods, are found to lead to remarkably consistent conclusions about the nature of recollection and familiarity, particularly when ceiling effects are avoided. For example, recollection is found to be more sensitive than familiarity to response speeding, division of attention, generation, semantic encoding, the effects of aging, and the amnestic effects of benzodiazepines, but it is less sensitive than familiarity to shifts in response criterion, fluency manipulations, forgetting over short retention intervals, and some perceptual manipulations. Moreover, neuropsychological and neuroimaging results indicate that the two processes rely on partially distinct neural substrates and provide support for models that assume that recollection relies on the hippocampus and prefrontal cortex, whereas familiarity relies on regions surrounding the hippocampus. Double dissociations produced by experimental manipulations at time of test indicate that the two processes are independent at retrieval, and single dissociations produced by study manipulations indicate that they are partially independent during encoding. Recollection is similar but not identical to free recall, whereas familiarity is similar to conceptual implicit memory, but is dissociable from perceptual implicit memory. Finally, the results indicate that recollection reflects a thresholdlike retrieval process that supports novel learning, whereas familiarity reflects a signal-detection process that can support novel learning only under certain conditions. The results verify a number of model predictions and prove useful in resolving several theoretical disagreements.
It has been proposed that the hippocampus selectively supports retrieval of contextual associations, but an alternative view holds that the hippocampus supports strong memories regardless of whether they contain contextual information. We employed a memory test that combined the 'Remember/Know' and source memory procedures, which allowed test items to be segregated both by memory strength (recognition accuracy) and, separately, by the quality of the contextual information that could be retrieved (indexed by the accuracy/confidence of a source memory judgment). As measured by fMRI, retrieval-related hippocampal activity tracked the quality of retrieved contextual information and not memory strength. These findings are consistent with the proposal that the hippocampus supports contextual recollection rather than recognition memory more generally.
Depressive symptoms often coexist with memory deficits in older adults and also are associated with incident cognitive decline in the elderly. However, little is known about the neural correlates of the association between depressive symptoms and memory deficits in nondemented elderly. Fifteen amnestic mild cognitive impairment (aMCI) and 20 cognitively normal (CN) subjects completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Multiple linear regression analysis was performed to test the main effects of the Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test delayed recall (RAVLT-DR) scores, and their interaction on the intrinsic amygdala functional connectivity (AFC) network activity. Severer depressive symptoms and memory deficits were found in the aMCI group than in the CN group. Partial correlation analysis identified that the RAVLT-DR scores were significantly correlated with the AFC network in the bilateral dorsolateral prefrontal cortex (DLPFC), dorsomedial and anterior prefrontal cortex, posterior cingulate cortex (PCC), middle occipital gyrus, right inferior parietal cortex, and left middle temporal gyrus (MTG). The GDS scores were positively correlated with the AFC network in the bilateral PCC and MTG, and left DLPFC. The interactive effects of the GDS and RAVLT-DR scores on the AFC network were seen in the bilateral PCC, MTG, and left DLPFC. These findings not only supported that there were interactive neural links between depressive symptoms and memory functions in nondemented elderly at the system level, but also demonstrated that R-fMRI has advantages in investigating the interactive nature of different neural networks involved in complex functions, such as emotion and cognition.
With emphasis on dimensional aspects of psychopathology in development of the upcoming DSM-V, we systematically review data on epidemiology, illness course, risk factors for, and consequences of late-life depressive syndromes not meeting DSM-IV-TR criteria for major depression or dysthymia. We termed these syndromes subthreshold depression, including minor depression and subsyndromal depression. We searched PubMed (1980-Jan 2010) using the terms: subsyndromal depression, subthreshold depression, and minor depression in combination with elderly, geriatric, older adult, and late-life. Data were extracted from 181 studies of late-life subthreshold depression. In older adults subthreshold depression was generally at least 2-3 times more prevalent (median community point prevalence 9.8%) than major depression. Prevalence of subthreshold depression was lower in community settings versus primary care and highest in long-term care settings. Approximately 8-10% of older persons with subthreshold depression developed major depression per year. The course of late-life subthreshold depression was more favorable than that of late-life major depression, but far from benign, with a median remission rate to non-depressed status of only 27% after ≥1 year. Prominent risk factors included female gender, medical burden, disability, and low social support; consequences included increased disability, greater healthcare utilization, and increased suicidal ideation. Heterogeneity of the data, especially related to definitions of subthreshold depression limit our ability to conduct meta-analysis. The high prevalence and associated adverse health outcomes of late-life subthreshold depression indicate the major public health significance of this condition and suggest a need for further research on its neurobiology and treatment. Such efforts could potentially lead to prevention of considerable morbidity for the growing number of older adults.