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Table 2. Demographic and clinical characteristics of the four cognitive-functional subgroups.
Demographic and clinical variables BD-P (n = 17) BD-M (n = 22) BD-DL (n = 69) Dementia (Positive Control) (n = 59) P-value† ‡ §
Sociodemographic variables
Age* 43.2 (±15.4) 55.2 (±15.6) 55.2 (±12.2) 70.7 (±9.6) <0.001‡
Sex (female) 15 (88.2%) 17 (77.3%) 52 (75.4%) 42 (71.2%) 0.59§
Ethnicity (white) 16 (94.1%) 20 (90.9%) 59 (85.5%) 30 (50.8%) <0.001§
Educational level (years)* 12.8 (±2.2) 12.3 (±3.8) 9.8 (±4.1) 10.4 (±6.9) 0.004‡
Clinical conditions
Hypertension 3 (17.6%) 7 (31.8%) 24 (34.8%) 44 (74.6%) <0.001§
Diabetes 3 (17.6%) 5 (22.7%) 22 (31.9%) 22 (37.3%) <0.001§
Clinical symptoms severity (CGI-S)* 3.2 (±1.1) 2.7 (±0.6) 4.2 (±1.1) 3.7 (±0.7) <0.001‡
Medications
Number of medications* 1.4 (±0.8) 1.2 (±0.7) 1.5 (±0.7) 0.386‡
Lithium use 7 (41.2%) 8 (36.4%) 23 (33.3%) 0 (0.0%) <0.001§
Antipsychotics use 12 (70.6%) 14 (63.6%) 59 (85.5%) 13 (22.0%) <0.001§
Symptom scales
COBRA* 9.6 (±5.7) 9.6 (±8.8) 21.5 (±10.6) <0.001‡
FAST* 10.9 (±5.6) 11.0 (±6.9) 37.0 (±11.9) <0.001‡
MADRS* 13.4 (±12.5) 7.8 (±8.2) 20.0 (±12.6) <0.001‡
YMRS* 3.0 (±4.6) 4.2 (±5.1) 5.3 (±6.3) 0.174‡
Interpersonal Relationship (FAST 17-21)* 1.7 (±1.8) 2.0 (±2.4) 5.7 (±3.6) <0.001‡
Legend: Values are presented as mean (± standard deviation) for continuous variables, and count (percentage) for categorical variables. Statistical tests compare differences across groups: † Analysis of Variance (ANOVA), ‡ Kruskal–Wallis test, § Chi-square test or Fisher’s exact test, as appropriate.
*Mean (±SD). Binary variables shown as count (percentage).† ANOVA  ‡ Kruskal-Wallis  § Chi-square or Fisher’s exact test

Logistic Regression – Univariate Analysis

Table 3: Univariate Logistic Regression analysis of predictors for the Dementia-like phenotype (BD-P vs BD-DL)
Variável_Final OR IC95 p-valor
Age 1.08 [1.03, 1.13] 0.002
Educational level (years) 0.77 [0.63, 0.92] 0.008
MADRS total score 1.05 [1.00, 1.10] 0.062
COBRA total score 1.17 [1.08, 1.30] <0.001
Interpersonal relationship (FAST 17–21) 1.66 [1.30, 2.28] <0.001
Diabetes (Yes) 2.18 [0.63, 10.18] 0.255
Hypertension (Yes) 2.49 [0.72, 11.56] 0.183
Sex (Female) 0.41 [0.06, 1.65] 0.264
Lithium use (Yes) 0.71 [0.24, 2.19] 0.544
Note:
Odds Ratio (OR) > 1 indicates increased risk for BD-DL; OR < 1 indicates protective factor. CI: Confidence Interval.

TABELA 1

Groups
Factor BD-P BD-M BD-DL Kruskal-Wallis Post hoc Effect size (r)
MMSE* 27.3 (±1.7) 24.4 (±2.6) 22.1 (±3.7) <0.001 BD-DL < BD-M < BD-P 0.58
RAVLT A1* 5.4 (±1.5) 4.4 (±1.6) 3.3 (±1.6) <0.001 BD-DL < BD-P, BD-M 0.46
RAVLT A7* 7.9 (±3.8) 4.8 (±2.8) 4.0 (±3.3) <0.001 BD-M, BD-DL < BD-P 0.39
Clock test* 3.7 (±1.2) 2.5 (±1.5) 2.7 (±1.8) 0.055 ns 0.23
Verbal Fluency (phonemic)* 13.5 (±5.9) 9.6 (±4.1) 8.5 (±4.4) 0.003 BD-DL < BD-P 0.36
Verbal Fluency (semantic)* 20.2 (±5.0) 15.4 (±4.5) 14.0 (±5.7) <0.001 BD-M, BD-DL < BD-P 0.40
TMT-A Time* 53.1 (±62.0) 84.8 (±98.9) 74.8 (±53.2) 0.002 BD-P < BD-M, BD-DL 0.37
Digit Span (forward)* 8.2 (±2.8) 7.1 (±1.8) 6.2 (±2.3) 0.002 BD-DL < BD-P, BD-M 0.33
Digit Span (backwards)* 5.0 (±2.3) 3.0 (±1.7) 3.3 (±1.4) 0.002 BD-M, BD-DL < BD-P 0.36
MoCA* 25.3 (±1.5) 19.7 (±3.1) 17.3 (±4.6) <0.001 BD-M, BD-DL < BD-P 0.69
MoCA MIS* 10.8 (±2.3) 7.7 (±3.3) 6.5 (±3.2) <0.001 BD-M, BD-DL < BD-P 0.48
Note: Group comparisons were conducted using Kruskal–Wallis tests. Post hoc comparisons used Dunn’s test with FDR correction. Effect sizes are reported as rank-biserial correlations (BD-P vs BD-DL).

Supplementary Table S1 — Neuropsychological scores by group (violin plot data)

Table S1. Neuropsychological scores by clinical group. Values are Median (Q1–Q3).
BD Groups
Variable BD-P BD-M BD-DL Dementia (PC)
Phonemic Fluency (Z-score) 0.5 (-0.1–1.3) -0.1 (-0.5–0.5) -0.3 (-0.7–0.1) -0.1 (-0.8–0.6)
Semantic Fluency (Z-score) 0.8 (0.3–1.3) -0.0 (-0.4–0.5) -0.4 (-0.9–0.5) -0.0 (-1.0–0.9)
RAVLT A1 (Raw) 5.0 (5.0–6.0) 5.0 (4.0–5.0) 3.0 (2.0–4.0) 2.0 (1.0–3.0)
RAVLT A7 (Raw) 8.0 (6.0–11.0) 4.0 (3.0–7.0) 3.5 (1.8–6.0) 0.0 (0.0–1.8)
Clock Test (Raw) 4.0 (3.0–5.0) 3.0 (2.0–3.0) 3.0 (1.0–4.0) 2.0 (0.0–5.0)
MMSE (Raw) 28.0 (26.0–29.0) 25.0 (22.0–26.0) 23.0 (20.0–24.0) 19.5 (16.0–27.0)
Note: Raw scores are reported for MMSE, RAVLT, and Clock Test. Fluency variables are reported as Z-scores normalized separately by reference pool (Internal vs. External).

Figura X. Perfil neuropsicológico comparativo entre fenótipos clínicos e coorte externa de demência. Os gráficos de violino representam a densidade de distribuição dos dados, enquanto os boxplots internos indicam a mediana e o intervalo interquartílico. Pontos individuais (jitter) representam cada sujeito da amostra. G1 - Dementia-like; Mild (BD-M); G3 - Preserved. As variáveis de fluência (Semântica e Fonética) foram normalizadas por escore-Z separadamente por pool de referência (Interno vs. Externo), enquanto as demais variáveis representam pontuações brutas (raw scores). Diferenças estatísticas significativas (\(p < 0,05\) no teste post-hoc de Dunn) entre os grupos internos estão indicadas na Tabela 2.