Table 1.

Summary of the included studies with longitudinal design

Authors	N	Age range and gender	Glioma/tumor subtype	Treatment	Neuropsychological tests and correction for practice (P)	Time points of testing (number of interval tests < 12m)	Main findings
Archibald et al.18	25	18–63years 12 male, 13 female	HGG	Surgery, RT and adjuvant CT	WAIS, WMS, ROCF, SRT TMT B, Monroe-Sherman Reading Comprehension, Design, Fluency – P: Not available	BL: 1–63 months after diagnosis FU: 6 monthly or yearly interval, with the last test at 68–102 months after diagnosis (1)	At baseline, the greatest impairment was observed in verbal memory and sustained attention. Verbal learning and flexibility in thinking had the greatest chance to decline over time.
Armstrong et al.19	26	18–69years 15 male, 11 female	Glioma WHO grades 1–2, pineal and pituitary tumour, non-invasive meningioma	WBRT after surgical biopsy, resection, or no surgical intervention.	Praxis, Finger Tapping Test, Bells Test, Auditory Selective Attention Test, Visual Continuous Performance Test, Sentence Repetition Test, COWAT, Animal Naming Test, PASAT, DSST, Digit Span, Word Span Test, RAVLT, Road Map Test, Visual Pursuits Test, ROCF, Visual Memory Span Test, BVRT, Biber Figure Learning Test, WCST- P: alternate forms	BL: 6 weeks after surgery, before RT FU: every year (until year 6) (0)	5 years after WBRT, patients showed cognitive decline in visual memory. Motor function, attention and executive functioning, language, verbal memory, information processing speed and visuospatial abilities did not deteriorate or even improved.
Bian et al.20	18	18–65years 10 male, 8 female	HGG	Surgery, RT and CT	MMSE, MoCA- P: not available	BL: Before RT FU: Post-RT, at 3,6,9, and 12 months post-RT (3)	No significant changes in cognitive functioning before treatment or at follow-up was observed.
Brown et al.21	187	>18years 105 male, 82 female	Supratentorial LGG	Tumor resection and RT: 50.4Gy or 64.8Gy	MMSE- P: not available	BL: study entry FU: at 1,2 and 5 years (0)	The minority of patients had a decrease in MMSE score. Most patients showed an increase. Recall and serial sevens showed more difficulties than other tests.
Brown et al.22	1244	18–84years 692 male, 552 female	HGG, gliosarcomas	RT and nitrosourea-based CT	MMSE – P: not available	BL: after surgery FU: at 6, 12, 18, and 24 months (1)	The tumor itself was the main cause of cognitive deterioration.
Butterbrod et al.23	263	Mean age: 53.2 years 164 male 99 female	Glioma WHO grade 2–4	Surgery and/or RT and/or CT	CNS Vital Signs, Digit Span, Letter Fluency- P: Standardized regression-based change scores	BL: 1 day before surgery FU: 3 and 12 months after surgery (1)	No significant effect of ε4 carrier status or interaction between time (T0–T12) and carrier status on any of the tests in the whole sample nor in the sample receiving adjuvant treatment.
Carbo et al.*,24	28	Mean age: 37 years, 22 male, 6 female	Glioma, cavernoma, cavernous hemangioma, MTS	Surgery	Categoric Fluency, RAVLT, SCWT, LDST- P: not available	BL: 3 months before surgery FU:12 months post-surgery (0)	Patients’ cognitive performance did not change significantly between baseline and post-surgery (group level)
Corn et al.25	209	20–82years 139 male, 70 female	Supratentorial GBM	Surgery, CT and RT	MMSE- P:RCI	BL: Before RT FU: at 4, 8 and 12 months after RT (2)	Cognitive function seemed to deteriorate over time, although cognitive impairment was more significant when the scores were adjusted for age and education.
Gondi et al.*,26	18	19–82years 10 male, 8 female	LGG, pituitary adenomas, vestibular schwannomas, meningiomas	Fractioned stereotactic RT	NART, WAIS, BNT, Token Test, Judgment of Line Orientation, Facial Recognition Test, Hooper Visual Organization Test, WMS-III, TMT, SCWT- P: standardized regression-based change scores	BL: Before RT FU: 12 and 18 months after RT(0)	A correlation was observed between fraction dose to the bilateral hippocampi and memory impairment in the long-term.
Gui et al.27	30	35–87 years 16 male, 14 female	GBM	Surgery, RT (NPC niche sparing) and TMZ	TMT A&B, COWAT, Coding, HVLT-R- P: Not available	BL: Before RT/CT FU: at 6 and 12 months after RT (1)	Lower doses to the hippocampi and the SVZ may reduce deterioration of verbal memory (HVLT-R)
Hartung et al.28	22	21–67 years 11 male, 11 female	LGG	Surgery and/or RT and/or CT	TMT, SCWT- P:RCI	BL: Before surgery FU: 3–18 months after surgery (0)	Disconnection of the lateral part of the dorsal stream might be correlated specifically with impaired set-shifting (changes in TMT) and not with inhibition (no changes in Stroop Task)
Hendriks et al.29	59	18–67years 34 male, 25 female	Gliomas WHO grade 1–3	Surgery and/or RT and/or CT	Digit Span, SCWT, TMT, DSST, ROCF, RAVLT, Location Learning Test, Memory Comparison Test, Categoric and Phonemic Word Fluency Test, BADS- P:not available	BL: 1 week before surgery FU: 1 year post-surgery (0)	Six patients showed cognitive improvement in working memory. Ten patients showed cognitive decline in attention, 9 in information processing speed, 7 in visual construction, 6 in both visual and verbal memory, and 4 in both working memory and executive functioning. The right hemisphere was the most vulnerable region for cognitive decline after surgery.
Jaspers et al.30	29	30–50years 18 male, 11 female	LGG	Surgery and RT	RAVLT- P: Standardized regression-based change scores	BL: Before treatment FU: 18 months after treatment (0)	Older patients and patients with a tumor in the left hemisphere of the brain had more risk for developing cognitive decline 18 months after treatment.
Laack et al.31	20	>18years 14 male, 6 female	LGG	Surgery and localized RT (50.4Gy or 64.8Gy)	MMSE, WAIS-R, RAVLT, BVRT, TMT, SCWT, COWAT- P: not available	BL: Before RT FU: Median of 18 months after RT (0)	At 1.5 years after treatment, no significant cognitive decline was observed in the high-, neither in the low-dose group.
Moretti et al.32	34	Mean age: 46 years	Glioma, cerebral lymphoma, and craniopharyngioma	Surgery or biopsy and RT (30–45Gy or 45–65Gy)	MMSE, Digit Span, Categoric and Phonemic Word Fluency, Mental and Written Calculation and Analogies.-P: Not available	BL: Mean scores before surgery and before RT FU: 12 months after RT (0)	Cognitive decline is related to the total radiation dose, the volume of the irradiated brain and the individual fraction size. < 35Gy: no cognitive impairment > 35Gy: cognitive decline
Moretti et al.7	114	Mean age: 45.2 years	GBM, WHO grade 2 gliomas, craniopharyngiomas, cerebral lymphomas, AC WHO grade 2–3, anaplastic patterns	Surgery or biopsy and/or RT and/or CT	MMSE, Digit Span, Semantic and Phonemic Fluency, Mental Calculation, Analogies- P:not available	BL: before surgery FU: after RT and 3,6 and 12 months after RT (3)	A cognitive and behaviour decline was observed in patients exposed to significant RT doses, 30–65 Gy. This decline was similar to what was typically observed in sVAD (dysexecutive functions, apathy, and gait alterations), but with a more rapid onset and with an overwhelming effect
Norrelgen et al.33	27	17–56years 17 male, 10 female	Gliomas WHO grade 2–3, cavernoma, GBM	Awake surgery	TROG-2, BNT, MBT, Token test, BeSS, Word Fluency (FAS, Animals, and Verbs), AQT, DLS, LS- P: Not available	BL: 3 weeks before surgery (mean) FU: 3 and 12 months post-surgery (1)	Overall high-level language ability was not significantly affected postoperatively at 3 and 12 months. However, semantic word fluency deteriorated postoperatively at 3 and 12 months follow-up, indicating a decline in processing speed of verbal material postoperatively.
Prabhu et al.34	287	22–79years 158 male, 129 female	Low-risk LGG, High-risk LGG	Surgery and RT with or without CT (PCV)	MMSE- P: Not available	BL: before RT FU: at year 1, 2, 3, 4, and 5 (0)	The majority of patients did not show cognitive decline.
Reijneveld et al.35	477	>18 years	LGG	RT vs. TMZ	MMSE- P: Not available	BL: Before treatment FU: Every 3 months after treatment up until 36 months (3)	Three years after treatment, no differences in cognitive functioning were established between the group who was treated with RT and the group who was treated with TMZ.
Sarubbo et al.36	12	19–63years 8 male, 4 female	LGG	Awake surgery	MMSE, Laiacona-Capitani Naming Test, Token Test-P: Not available	BL: Before surgery FU: each follow-up for 3 years, no time points defined(unknown)	Cognitive functioning did not worsen in this cohort, and even improved in two patients. Language did not decline in any of the patients.
Sherman et al.37	20	22–56years 13 male, 7 female	LGG	Surgery (or biopsy) and proton RT	WAIS-III, BNT, ANT, CPT-II, TMT A&B, COWAT, HVLT, BVMT- P:RCI	BL: before RT FU: at 12, 24, 36, 48, and 60 months post-RT (0)	Cognitive stability or improvement in visuo-spatial abilities and executive functioning was observed. Improvement in verbal memory was greater in patients with left-sided tumors.
Torres et al.38	22	>18years 11 male, 11 female	Glioma, meningioma, adenoma, ependymoma	Surgery and RT	Shipley Institute of Living Scale, SRT, 10/36 Spatial Recall Test, LDST, Digit Span, TMT-P: not available	BL: before RT FU: at 3, 6, 12, and 24 months post-RT (2)	Cognitive functioning did not decline in the first 2 years after RT, but a mild improvement in recall and verbal memory was observed.
Vigliani et al.39	33	24–49years 12 male, 5 female	LGG or anaplastic AC	Surgery (or biopsy) with or without RT and/or CT	SCWT, WAIS, Reaction Time, Verbal and Visual Span, RPM, WMS, Word and Design Series, ROCF—P: Not available	BL: After surgery, before RT FU: at 6, 12, 24, 36, and 48 months after RT (1)	Attention and memory were impaired within 6 months after RT. However, no cognitive decline was observed 1-2 years after RT. The risk of cognitive decline was higher in older patients than in young adults.
Wang et al.40	289	>18years	Anaplastic ODG	RT with or without CT (PCV)	MMSE-P: Not available	BL: Before RT/CT FU: at 12, 16, 20, 24, 30, 36, 44,50,56, 62, 68, and 74 months (0)	No difference in scores on the MMSE between 2 groups (RT+PCV or RT alone) High MMSE scores predicted a lower risk of death. Tumor progression caused cognitive decline.
Wang et al.41	229	>18years 135 male, 94 female	HGG	Surgery and RT and CT	MoCa- P: Not available	BL: After surgery, pre-RT FU: at 3, 6, 9, 12, 15, and 18 months after RT (3)	67% of patients showed cognitive impairment, statistically significant at 9 months follow-up. Unmethylated MGMT promoter methylation, and residual tumor volume >5.58cm3 were independent risk factors for cognitive impairment
Weller et al.42	141	18–70 years	GBM	Surgery, RT and CT (TMZ or TMZ-lomustine)	TMT A and B, WAIS Digit Span (forward/backward), COWAT, Verbal Fluency, Regensburger Wortflüssigkeitstest, MMSE- P:RCI	BL: Before RT FU: Every 3 (MMSE) and 6 months (NOA07 battery) until 48 months (3 and 1)	Differences in MMSE were in favour of the TMZ group but were not clinically relevant. No significant difference between the groups in any subtest of the cognitive test battery was observed.
Yavas et al.43	43	18–69years 27 male, 16 female	LGG	Surgery (or biopsy) and RT	MMSE-P: Not available	BL: after surgery, before RT FU: at 3,6,12, 18, 24, 30, and 36 months after RT (2)	Recall score (MMSE) declined in the first 3 years after treatment. Anti-epileptic drugs had a negative effect on cognitive functioning.

Note. WHO = World Health Organization; LGG = low-grade glioma; HGG = high-grade glioma; AC= astrocytoma; ODG= oligodendroglioma; GBM = glioblastoma multiforme; MTS = mesial temporal sclerosis; RT = radiotherapy; WBRT = whole brain radiation; CT = chemotherapy; PCV = procarbazine, lomustine and vincristine; TMZ = temozolomide; ANT = Auditory naming test; AQT = A Quick Test of Cognitive Speed; BADS = Behavioural Assessment of the Dysexecutive Syndrome; BeSS = Behavioral and Emotional Screening System; BNT = Boston Naming Test; BVMT = Brief visuospatial memory test; BVRT = Benton Visual Retention Test; COWAT = Controlled Oral Word Association Test; CPT-II = Conner’s continuous performance test (Second edition); DLS = Diagnostiskt material för analys av läs- och skrivförmåga; DSST = Digit Symbol Substitution test; HVLT(-R) = Hopkins Verbal Learning Test (-Revised); LDST = Letter-digit substitution Test; LS = Klassdiagnoser för högstadiet och gymnasiet – Läs- & skrivdiagnostik (LS); MBT= Months Backwards Test; MMSE = Mini Mental State Exam; MoCA = Montreal Cognitive Assessment; NART = National Adult Reading Test; PASAT = Paced Auditory Serial Addition Test; (R)AVLT = Rey Auditory-Verbal Learning Test; ROCF= Rey-Osterrieth Complex Figure; RPM = Raven Progressive Matrices; SCWT = Stroop Color and Word Test; SRT = Buschke Selective Reminding Test; TMT = Trail Making Test; TROG-2= Test for reception of Grammar-2; WAIS(-R) = Wechsler Adult Intelligence Scale (Revised); WCST = Wisconsin Card Sorting Test; WMS = Wechsler Memory Scale; P = practice effects; RCI= Reliable Change Index; BL = baseline; FU = follow-up; NPC = neural progenitor cell; SVZ = subventrical zone; sVAD = subcortical vascular dementia..*: included in both longitudinal and cross-sectional meta-analyses.