Table 1: Summary of the studies included in this review.

Autors (Year) (Type) n M/F Age Body fluid measured Memory Attetion Executive Functions Visuospatial abilities and psychomotor Perception Inteligence Global Cognition Neuropsychocological Assement Instruments Result Methodological aspects Ref
Chua et al (2014)34 (longitudinal study) 218 PMW 0/218 59,7 Blood samples X A comprehensive battery of 13-item neuropsychological tests. The analyses demonstrated no significant relation between DHEAS level and cognitive function in midlife, postmenopausal women.
  • Adults and Elderly
  • Set of tests
  • Female population
[34]
Merritt et al (2012)38 (longitudinal study) 48 PMW 0/48 63,5 +/- 6,85 * x
  • Mini Mental State
Examination (MMSE)
  • Digit Span Forward test (Wechsler Memory Scale-Third Edition)
  • Digit Span Backward test (Wechsler Memory Scale-Third Edition)
  • Verbal Span Performance
  • Modified Spenberg Paradigm
Despite this substantial change in the hormonal milieu, DHEA administration produced no beneficial effects on cognitive performance in the digit span, verbal span, or modified Sternberg paradigm tasks.
  • Elderly
  • Body fluid measured wasn’t cited
  • Set of instruments
  • Female population
[38]
Fukai et al (2009)23 (cross-sectional study) 208 EFD 108 / 100 70 – 95 Years (M) 70 – 93 Years (W) Blood samples x
  • Hasegawa Dementia Scale – Revised
Only in men DHEA(-S) was associated with cognitive function.
  • Elderly
  • Scale
  • Male and Female population
[23]
Alfaro et al (2008)5 (cross-sectional study) 313 E 153 / 160 76,7 +/- 5,4 (M) 77,3 +/- 6,4 (W) Blood samples x x
  • Mini Mental State

Examination (MMSE)
In women, adrenal steroids showed a negative correlation with global cognition. For memory function, DHEA also correlated negatively in women. No relationships with cognition were observed in men for any of the steroids.
  • Elderly
  • Screaming test
  • Male and Female population
[5]
Kritz-Silverstein et al (2008)39 (longitudinal survey) 112 DT 113 P 110 / 115 68,7 +/- 7,9 Blood samples x x
  • Category Fluency
  • Word List Memory
  • Word List Recall
There were no differences between the DHEA and placebo groups in change over time in cognitive function (P>.10). DHEA supplementation has no benefit on cognitive performance in healthy older adults, and it should not be recommended for that purpose in the general population.
  • Elderly
  • Set of tests
  • Male and Female population
[39]
Davis et al (2008)32 (cross-sectional study) 295 W 0/295 55 +/- 12,8 Blood samples x x x
  • Controlled Oral Word Association Test score
  • Digit Span Forward test (Wechsler Memory Scale-Third Edition)
  • Digit Span Backward test (Wechsler Memory Scale-Third Edition)
  • California Verbal Learning Test Immediate
  • Wechsler Memory Scale-Third Edition
  • Stroop Color-Naming Interference Test
  • Trail Making Test B (TMTB)
DHEAS term made a significant independent Positive contribution to the Controlled Oral Word Association Test score, a measure of  executive function. In addition, women with a DHEAS level in the highest tertile who also had more than 12 yr of education performed better on both Digit Span Forward and Digit Span Backward tests, which are tests of simple concentration and working memory, respectively.
  • Adults and Elderly
  • Set of tests
  • Female population
[32]
Kędziora-Kornatowska et al (2007)27 (cross-sectional study) 103 EHW 25C 0/128 70,7 +/- 7,3 Blood samples x
  • Mini-Mental State Examination (MMSE)
Statistically significantly lower DHEA-S concentration was observed in patients with benign disorders of cognitive functions and depression compared with patients with correct MMSE
  • Elderly
  • Screaming test
  • Female population
[27]
Haren et al (2007)6 (cross-sectional study) 124 EHM 124/0 56,1 +/- 4,4 Blood samples x
  • Mini-Mental State Examination (MMSE)
  • Trail-making test (TMT)
Higher DHEAS levels were associated with higher mini-mental state examination (MMSE) score (b =0.098, p= 0.008).
  • Adults
  • Screaming test plus gold pattern test
  • Male population
[6]
Goldman e Glei (2007)22 (longitudinal survey) 836 E * 54 and older Blood samples x Items from:
  • Short Portable Mental Status Questionnaire
  • Rey Auditory Verbal Learning Test
  • Digits Backward test
In most men low levels of DHEAS are associated with poor cognitive function . There are no significant associations among women.
  • Adults and Elderly
  • Set of tests
  • Male and Female
[22]
Arai et al (2006)26 (cross-sectional) 145 E 58/87 75,6 +/- 0.56 Blood samples x
  • Mini-Mental State Examination (MMSE)
The levels of DHEA e DHEA-S were not associated with MMSE.
  • Elderly
  • Screaming test
  • Male and Female population
[26]
Parsons et al (2006)29 (longitudinal survey) 11 DT 9P 0/20 PMW 46-66 years Blood samples x
  • California Verbal Learning

Test (CVLT)
  • Wechsler Adult Intelligence Scale-Revised (WAIS-R)
  • Digit Span Forward
  • Digit Span Backward
  • Trail Making Test A and B
  • Golden

Stroop Test
  • Token Test
  • Category Fluency
  • Boston Naming Test
  • Test of

Nonverbal Intelligence-2 (TONI-2)
  • Judgment of Line Orientation
An increase in negative associations between DHEA(S) levels and cognition was found at completion. Increased cortisol does not explain the cognitive deficits associated with DHEA, suggesting a direct negative effect of exogenous DHEA on cognition.
  • Adults and Elderly
  • Set of tests
  • Female population
[29]
Alhaj et al (2006)36 (longitudinal survey) 24 YM 24/0 23,6 +/- 5,1 Saliva samples x
  • Visual analogue scales (VASs)
DHEA administration led to a reduction in evening cortisol concentrations and improved VAS mood and memory. Recollection accuracy in the episodic memory test was significantly improved following DHEA administration.
  • Young
  • Scale
  • Male population
[36]
Azurmendi et al (2005)41 (cross-sectional) 129 C 60/69 5 years 11 months mean age Saliva samples x
  • Kaufman Brief Intelligence Test (K-BIT)
DHEA was not a good predictor for fluid intelligence and crystallized intelligence in both genders.
  • Children
  • Set of tests
  • Male and Female population
[41]
Fonda et al (2005)9 (cross-sectional) 981 EHM 981/0 62,66 years Blood samples x x x
  • Backward Digit Span test
  • Digit Symbol Substitution test
  • Figural Relations test
The direct effects of hormones on cognition are not significant when salient factors (educational attainment, health conditions and behaviors, body mass index, and depression) are considered.
  • Elderly
  • Set of tests
  • Male population
[9]
Glei et al (2004)21 (cross-sectional) 967 E * 54 and older Blood and urine samples x
  • 12 items from the

modified Short Portable Mental Status Questionnaire
  • Rey Auditory Verbal Learning

Test
  • Digits

Backward test.
Results reveal that higher levels of DHEAS are associated with better cognitive function (among women but not men)
  • Adults and Elderly
  • Set of tests
  • Male and female population
[21]
Hirshman et al (2004)37 (longitudinal study) 6 PMW 0/6 53-68 years Blood samples x x x
  • Recognition Memory test
  • Digit Span
  • Perceptual Identification
  • Visual Attetion Vigilance
Our results demonstrated that estrogens produced a positive effect on recognition memory and perceptual identification, while androgens produced a negative effect. Androgens also produced a negative effect on visual attentional vigilance.
  • Aldults and Elderly
  • Set of tests
  • Female population
[37]
Nierkerk et al (2001)34 (longitudinal study) 46 (EM) 46/0 62-76 years Saliva samples x
  • Word list memory
  • Object location memory
  • Choice reaction time (CRT)
  • Visual search
A higher morning cortisol/DHEA ratio was also associated with lower visuo-spatial memory performance. But no significant effects of DHEA treatment  were observed on any of the trial outcomes.
  • Adults and Elderly
  • Set of tests
  • Male population
[34]
Aleman et al (2001)33 (cross-sectional) 25 EHM 25/0 69,1 years Blood samples x x
  • Information (WAIS)
  • Vocabulary (WAIS)
  • Benton

Judgement of Line Orientation
  • Brus Reading Test
  • Block Design (WAIS)
  • Digit Symbol (WAIS)
  • Concept Shifting Task
  • Dutch version of the Rey Auditory Verbal Learning Task.
Circulating levels of DHEAS were not associated with any of the neuropsychological measures.
  • Elderly
  • Set of tests
  • Male population
[33]
Moffat et al (2000)7 (longitudinal study) 883 EHM 883/0 22-91 years Blood samples x
  • Benton Visual Retention test (BVRT)
  • Free and Cued Selective Reminding Test
  • Mini-Mental State Examination (MMSE)
  • Blessed Information-Memory-Concentration Test
  • 2 tests of mental status assessing memory, visual construction and attention
  • Semantic and phomenic word fluency tests
  • Trail-Making Tests (parts A and B)
Decline in endogenous DHEAS concentration is independent of cognitive status and cognitive decline in healthy aging men.
  • Young, Adults and Elderly
  • Set of tests
  • Male population
[7]
Carlson and Sherwin (1999)25 (longitudinal study) 60 E 23/37 72.1 and 73.4 years Blood samples x
  • Weschler

Memory Scale (WMS)
  • Paragraph

Recall
  • Paired-Associates
  • Selective Reminding Test
  • WMS-Revised

Figural Memory
  • Visual Paired-Associates
  • Visual Reproduction

subtests
  • Digit Span Forward and Backward WMS-R Visual Memory Span
  • Category Retrieval Test
Results failed to provide any evidence that DHEAS is protective against declarative memory decline with aging.
  • Small population
  • Elderly
  • Set of tests
  • Male and Female population
[25]
Kalmijn et al (1998)28 (longitudinal study) 189 E * 67.3 +/- 5.7 Blood samples x
  • Mini-Mental State Examination (MMSE)
There was an inverse, but nonsignificant, association between DHEAS and cognitive impairment and decline.
  • Medium population
  • Elderly
  • Screaming test
  • Male and Female population
[28]
Yaffer et al (1998)8 (longitudinal study) 394 EHW 0/394 65 and older Blood samples x
  • Mini-Mental State Examination (MMSE)
  • Trails B
  • Digit Symbol
DHEAS levels declined with age, as expected. There was no consistent association of DHEAS quartile or log DHEAS with any of the four outcomes, even after multivariate adjustment.
  • Large population
  • Elderly
  • Set of tests
  • Female population
[8]
Carlson and Sherwin (1998)24 (cross-sectional study) 86 E 41/55 72.19+/-5.6 years Blood samples x
  • Paragraph

Recall
  • Paired-Associates
  • Selective Reminding Test
  • Figural Memory
  • Visual Paired-Associates
  • Visual Reproduction

subtests
  • Digit Span Forward and Backward
  • Category Retrieval Test
No significant correlations were found between any of the hormones or the DHEAS/CRT ratio and scores on any of the neuropsychological tests.
  • Small population
  • Elderly
  • Set of tests
  • Male and Female population
[24]
Wolf et all (1998)35 (longitudinal study) 17 E 17/0 71.1 ± 1.7 years Blood samples x
  • Picture memory test
  • City map test
  • Verbal fluency
DHEA treatment did not enhance memory
  • Small population
  • Elderly
  • Set of tests
  • Male population
[35]
Wolf et al (1997)40 (longitudinal study) 40 E 25/15 69,4 +/- 1,2 (M) 69,1 +/- 1,7 (W) Blood samples x x x
  • Concentration
  • Picture Memory test
  • Stroop test
  • Digit Span forward and backwards
  • Number connecting
  • Auditory verbal learning test
DHEA replacement had no strong beneficial effect on any of the measured psychological or cognitive parameters in either sex (all P. 0.20).
  • Small population
  • Elderly
  • Set of tests
  • Male and Female population
[40]

Legend: DP – Depressed Pacients; C – Controls; PMW – Postmenopausal women; EFD – Eldery with Functional Decline; E – Eldery; M- Men; W – Women; EHW – Eldery Healthy Women; YM – Young Men; EHM – Eldery Healthy Men; P – Placebo; DT – DHEA Treatment; *unspecified.

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