Table 1.
Studies where specific cognitive functions are examined.
| Study | Study Design | Sample Size | Disease | Cognitive Domains | Neuropsychological Tests | Results (Association between HCy Levels and Cognitive Functions) |
|---|---|---|---|---|---|---|
| Subjects with dementia | ||||||
| [94] | CS | 325 | 27 SMC, 142 MCI, 139 AD, 17 VaD | Memory, language, executive functions, attention, and visuoconstructive functions |
MMSE, Interview for Deterioration in Daily Living in Dementia, CDR, GDS, BDRS, CDT, WAIS (logical memory), FCRST, BVRT, CERAD (word list), BNT, Category-specific names test, SCWT, RPM, TMT A and B, Geometric figure copy | Significant relationship between HCy and performance in visuoconstructive functions |
| [145] | CS | 1112 | 768 HC, 133 MCI, 211 AD | Short-term memory, long-term memory and global cognitive status |
Four neuropsychological composite z-scores were computed: 1. Short-term episodic memory: logical Memory 1–Story A, CVLT-II immediate recall, RCFT 3-minute delay. 2. Long-term episodic memory:logical memory II, CVLT-II delayed recall, and RCFT 30-minutes delay. 3. Total episodic memory: all the tests from both sets 1 and 2 above. 4. Global cognitive: SCWT incongruent trials, category fluency switching, digit symbol coding, and the tests used for the Total episodic memory composite z-score. |
Composite z-scores of short- and long-term episodic memory, total episodic memory, and global cognition all showed significant negative correlations with HCy, in all clinical categories |
| [146] | CS | 323 | AD | Memory, language, visuoperception, visuospatial abilities, executive functions, attention, constructional praxis and ideomotor praxis |
MMSE, CPM, Digit span, Corsi’s Blocks, RAVLT, RCFT B, SCWT, Luria’s Motor Planning Test, Overlapping Figures of L.G., AB, Verbal Fluency, Phonological fluency, Naming, Reading, Word comprehension | HHCy was associated with poor performance on memory tasks and on Luria’s Motor planning test |
| [147] | CS | 52 | 26 MCI, 26 HC | Striatal and hippocampal functions | MMSE, CDR, GDS. Cognitive task: Learning-and-Generalization test |
Total HCy levels correlated positively with generalization errors, but not with learning errors |
| Healthy subjects | ||||||
| [107] | L | 909 (longitudinal data on 679) |
Elderly HC | Memory, visuospatial abilities and language | BNT, controlled word association test, category naming, complex ideational material subtest, Boston Diagnostic Aphasia Evaluation (sentence repetition); WAIS-R similarities subtest, selective reminding test, non verbal identities and oddities of the DRS, Rosen Drawing Test, BVRT | High HCy levels not related to decline in memory scores over time |
| [148] | CS | 21 | Middle-aged HC | Memory | Ö-VMPT, WMS,visual memory test | Increased HCy associated with lower memory score |
| [149] | L | 180 | Adult HC | Memory and attention | MMSE, CVLT, DRS, SCWT | HCy levels correlated with SCWT baseline and follow-up scores. Change rates of HCy and change rates of SCWT scores also correlated |
| [150] | L | 182 | Older HC with hypertension | Speed of cognition, attention, episodic memory, working memory and executive functions | MMSE, computerized assessment battery and executive function tests, TMT A and B, Verbal fluency (FAS), Category fluency (Animals) | Higher HCy associated with more severe cognitive decline in speed of cognition, episodic memory and executive function |
| [151] | L | 2189 | Elderly HC (community-dwelling) | Memory | Kendrick Object Learning Test | Subjects with memory deficit had higher HCy and lower folate at follow-up |
| [152] | CS | 1140 | Randomly selected adult HC | Language conceptual reasoning, simple motor and psychomotor speed, eye-hand coordination/manual dexterity, executive functions, memory and visuoconstruction/visuoperception |
BNT, Category fluency, Letter fluency, CPM, FTT (dominant and nondominant), Simple reaction time, Purdue pegboard (dominant, non-dominant and both hands), Purdue pegboard assembly, SCWT, TMT A and B, RAVLT, Visual memory and learning, RCFT-delayed recall 36, DS paired associate learning, RCFT-copy |
Elevated HCy levels associated with poorer scores in all tested cognitive domains |
| [153] | L | 321 | Elderly HC (men) | Memory, language and spatial functions |
MMSE, backward digit span, Word-list memory test, verbal fluency, constructional praxis |
HCy associated with decline in constructional praxis, (spatial copying) |
| [154] | L | 1257 (longitudinal data on 1076) | Older HC | Memory, information processing speed, reasoning |
MMSE, Auditory Verbal Learning Task, Coding Task, CPM | Higher HCy at baseline was negatively associated with prolonged lower cognitive functioning and a faster rate of decline in information processing speed and fluid intelligence |
| [155] | CS | 400 | HC (men, age 40–80) | Short-term memory, speed of information processing, long-term memory, word fluency, cognitive flexibility and verbal intelligence |
MMSE, Digit span, DS, RAVLT, Doors test, Verbal fluency (letters N and A, animals, and occupations), TMT A and B, Dutch Adult Reading Test |
HCy associated with processing capacity and speed |
| [156] | CS | 639 | HC | Memory, attention | Electronic Memory Span apparatus, electronic Attention Span apparatus, Functional Activities Questionnaire | Negative correlation between HCy and: attention span, delayed (but not immediate) memory recall |
| [157] | CS | 200 | HC (women, age 56–67) | Verbal and working memory, executive functions, intelligence |
CVLT-II, Ten unrelated words, WAIS Letter-Number Sequencing, NART-R |
HHCy associated with poor performance on combined score of verbal and working memory |
| [158] | CS | 170 | HC (post-menopausal women) | Memory, executive functions, psychomotor speed, reaction time, attention and cognitive plasticity |
MoCA, verbal memory test, FTT, SDMT, SCWT, SAT, continuous performance test | HHCy correlated with increased risk of de- cline in executive functions, complex attention, cognitive flexibility, and memory |
| [159] | CS | 228 | HC (community-dwelling) | Memory, executive functions and language. Factor analysis was used to summarize them into two orthogonal factors: memory and executive/language factors |
MMSE, CDR, immediate recall, delayed recall, recognition, savings, TMT A and B, diamond cancellation, letter cancellation, animal fluency, Shipley vocabulary, BNT | In very old, non demented community dwellers, high HCy levels associated with poor executive-language functioning but not with poor memory |
| [160] | CS | 466 | HC | Intelligence, psychomotor processing speed, verbal fluency, category fluency and memory | MMSE, NART-R, WAIS—III-digit symbol coding, Verbal fluency (FAS test and animal fluency), WMS |
HCy consistently associated with poorer performance in tests assessing visual memory and verbal recall |
| [161] | CS | 3914 | HC, age > 65 | Verbal fluency, attention, memory |
MMSE, The Isaacs Set Test (colors, animals, fruits, cities), TMT A and B, BVRT, Five-Word Memory Test | HCy associated with Benton Visual Retention Test and Trail Making Test |
| [162] | CS | 2096 | HC (dementia- and stroke-free) | Abstract reasoning, memory, language, executive functions |
WAIS (Similarities subtest, Paired-Associates Learning), Logical Memory (immediate recall; delayed recall; delayed recognition), Visual Reproductions (immediate recall; delayed recall; delayed recognition), Halstead-Reitan test (trails A and B), Hooper Visual Organization Test, BNT |
Older adults showed negative association between HCy and several cognitive tasks: abstract reasoning; verbal and visual memory; concentration, scanning, tracking, executive performance; visual organization; object naming and language. No such effects were found in younger and middle-aged adults |
| [163] | L | 144 | HC | Cognitive speed attention and information processing memory |
Letter-Digit Coding test, SCWT, Word Learning Test; Delayed Recall |
HCy correlated negatively with cognitive performance on Word Learning Test at baseline. Baseline HCy correlated negatively with follow up scores (up to 6-years) on SCWT and Word Learning Test |
| [164] | CS | Baseline: 1241; 2-years FU: 1151; 3-years 986; 4-years 782 |
Middle-aged HC | Attention and psychomotor speed | MMSE, TMT B, DSST of the WAIS-R, FTT | Higher concentrations of HCy related with poorer performance on all neuropsychological tests |
| [165] | CS | 451 | Middle-aged HC | Attention, memory, executive function, information processing speed, visuospatial and constructional ability |
MMSE, ADL, Digit Span, Spatial Span, RAVLT, Visual Reproduction, Categorical Verbal Fluency, Design Fluency, SDMT, TMT A and B, Block Design | HCy specifically associated with constructional ability and information processing speed, whereas folate was associated specifically with episodic memory and language ability |
| [166] | L | 274 | HC | Global cognition, episodic memory, executive functions, language, psychomotor speed | MMSE, immediate word recall test, SCWT, category fluency test, bimanual Purdue Pegboard test, letter-digit substitution test | High baseline HCy associated with poor episodic memory, executive functions and verbal expression |
| [167] | CS | 334 | HC from the Aberdeen 1921 (N = 186) and 1936 (N = 148) Birth Cohorts | Memory, intelligence, language, attention, executive functions and visuospatial functions |
MMSE, NART, RPM, RAVLT, WAIS (DS and block design subtests) | In 1921 Cohort, HCy negatively correlated with RPM, DS, and block design scores |
| [168] | CS | 2470 | HC (age > 60) | Memory | MMSE, delayed story recall, delayed word recall | HHCy was related to poor memory recall |
| [169] | CS | 1077 | Elderly HC | Psychomotor speed and memory |
MMSE, Abbreviated SCWT, Letter-Digit Substitution Task,Verbal fluency test, Paper-and-Pencil Memory Scanning Task, 15-word verbal learning test (based on RAVLT) |
Increasing HCy levels associated with lower psychomotor speed and memory scores |
Legend: AD = Alzheimer’s disease; CERAD = Consortium to Establish a Registry for Alzheimer’s Disease; CS = cross-sectional study; FU = follow-up; HC = healthy controls/subjects; HCy = homocysteine; HHCy = hyperhomocysteinemia; AB = Apraxia Battery; ADL = Activities of Daily Living; BDRS = Blessed Dementia Rating Scale; BNT = Boston naming test; BVRT = Benton Visual Retention Test; CDR = Clinical Dementia Rating Scale; CDT = Clock drawing test; CPM = Raven Coloured Progressive Matrices; CVLT/CVLT-II = California Verbal Learning Test; DRS = Mattis Dementia Rating Scale; DS = Digit Symbol; FCRST = Free and cued selective reminding test; FTT = Finger Tapping Test; GDS = Global Deterioration Scale; L = longitudinal study; MCI = Mild Cognitive Impairment; MMSE = Mini-Mental Status Examination; MoCA = Montreal Cognitive Assessment; NART-R = National Adult Reading Test—Revised; Ő-VMPT = Őktem—Verbal Memory Processes Test; RAVLT = Rey Auditory Verbal Learning Test; RCFT = Rey Complex Figure Test; RPM = Raven’s Progressive Matrices; SAT = Shifting Attention Test; SCWT = Stroop Color and Word Test; SDMT = Symbol Digit Modalities Test; SMC = Subjective Memory Complaint; TMT = Trail Making Test; WAIS (-R) = Wechsler Adult Intelligence Scale (Revised); WMS = Wechsler Memory Scale.