ADC Uniform Dataset (UDS): The Neuropsychologic test battery

Minimum data set in making for over ten years.  A spanish version of the UDS is available at https://www.alz.washington.edu.  Standard scoring is available at UDS Guidebook and Appendix, and later Neuropsychological Test Instructions, distributed to ADC's.  Version 2 differs in that logical memory story 2 delayed recall is done at 20 not 30 minutes with cueing with one detail from story now given.  Visuospatial measures were not used.  Focus of initial battery was Attention, speed of processing, executive function, episodic memory, and language.  Tests were selected by the panel with comments.  Tests utilized, with mean, sd, Q25, Q75, median and range for normals indicated:

 

1.  MMSE with a separate score for orientation out of ten -- note that its insensitive for dementia but is useful to tag milestones once dementia is established.  MMSE 29,1.3, 28, 30, 29, 17-20; Orientation items only: 9.7, 0.9, 10,10,10, 0-10.

 

2.  Digit Span Test from WMS -R, with 2 scores derived, namely total trials and longest digit sequence reproduced.

Digit span forward total trials:  8.6,2.1, 7,10,9, 1-12.

Digit span forward longest sequence:  6.7, 1.1, 6,8, 7, 0-8.

Digit span backwards total trials:  6.9, 2.2, 5,8,7,-12

Digit span backwards longest sequence: 5, 1.2, 4,6,5,1-7

 

3.  Trailmaking Test Parts A and B with standard rules but time limits of 150 seconds for Part A and 300 seconds for Part B. 

 

Part A Time in seconds:  34.6, 15.4, 25,40,31, 11-150.

Part B in seconds:  90.3, 50, 59, 105, 10-300

4.  Digit Symbol Coding from WAIS-R standard, with the score the total number of items completed in 90 seconds. Usually WMS R was used.

 

5. Logical memory stories--Immediate recall, and delayed recall. Test required at least 20 minute delay for delayed recall with notation of amount of time used for the delay.  Cue was given for second story. 

 

logical memory A total units, immediate recall  13.9 , 3.9, 11,17,14, 0-25

logical memory A delayed recall  12.6, 4.3, 10,16,13, 0-25

 

6.  Word lists were not used due to variability in implementation but centers were encouraged to use one and study its relationship to logical memory stories.

 

7.  Boston Naming Test short version using odd items, with discontinuation after six consecutive failures.  The score was the number named within a 20 second time limit plus the number named correctly with a semantic cue. 

 

27.2 , 3.2, 26, 29, 28, 2-30

 

8.  Verbal fluency was assessed using animal and vegetable list generation in one minute.

 

animals in 60 seconds:  20 , 5.6, 16,24, 20, 1-54

vegetable:  14.7, 4.4, 12,17,15,1-63.

 

9.  Additional items used:  FAQ (functional assessment questionnaire), behavioral symptoms from NPI-Q short form), and Geriatric Depression Scale. 

 

10.Inability to respond due to physical barriers was noted.

The non public domain items (most of test) were given in cooperation with manufacturers and consent.  Entire battery required 3-40 minutes was given annually.  Paper gives normal values.  Ceiling effects were obtained with perfect or nearly perfect scores on digit span forward and backwards (cannot exceed 8 and 7 respectively), BNT, MMSE orientation score, and total score.  On other tests some outlier scores were found (584/3268 had one or two outlier scores, 61 had 3 or more). 

 

 

Age, sex and education (demographics) were associated with nearly all results.  Males and females differed on more than half of test results.    Future tests will take into account additional qualitative information such as number of incorrect lines on the TMT.  Longitudinal studies will help separate abnormal from peak performance

CVLT performance by patients with focal frontal lesions

Alexander MP et al., Brain 2003.

CVLT has many measures. 
Immediate free recall-- posterior LDF (dorsolateral frontal) performed worse, than other frontal areas
List A first trial-- posterior LDF and PMF (posterior medial frontal) were most impaired
Trial by groups-- left LDF had flattest learning curve. 
Primacy/recency and serial position had no effects by group.
List B-- proactive interference was not present in any group
Recognition memory-- posterior LDF group and posterior RDF group performed worst. Recognition hits were not different, difference was due to more false alarms.
Discriminibility and response bias-- the post LDF performed worse than all except post RDF.
Short delayed free recall-- post LDF was worse than controls.  Ant RDF & PMF were different than controls. 
Long delay free recall-- post LDF worse than all groups except ant LDF & PMF.
Long delay cued recall similar to above.
Intrusions and double recalls-- no significant differences.
Inconsistency score-- post LDF was worse than all except post RDF
Subjective semantic organization-- RDF post worse.

Summary-- Immediate free recall was worse post LDF> PMF (esp bilateral involving septal area)> post RDF.  This was also true for delayed free recall short and long, and for learning curve for trial 1-5.  For recognition only LDF was impaired due to more false alarms. 

In a prior study, Stuss et al. found more double recalls in post. RDF group, not seen in this study although p=0.11.  Abnormalities cannot be attributed to PI, to serial position effect, or defective primary memory. 

MS as a disconnection syndrome

Dineen RA et al.  Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis.  Brain 2009;132: 239-249

Authors use DTI MRI and neuropsychology to try to correlate white matter specific disconnections with cognitive disorders in MS.Without delving into methodology, PASAT scores correlated with splenium and body of corpus callosum, parieto-occipital radiations of the forceps major, left cingulum, the right inferior longitudinal fasciculus running into the left temporal lobe, parietal tracts and portions of the left superior longitudinal fasciculus, and the parietal arcs of the arcuate fasciculi bilaterally.

The Benton Visual Retention Test correlated with lesions in splenium and body of the corpus callosum, the parietal and occipital projections of the forceps major bilaterally, the left inferior longitudinal fasciculus running into the temporal lobe, the left arcuate fasciculus, the left cingulum, the anterior portion and tail of the fornix, the white matter of the right parietal and medial occipital lobes.  Te right temporal lobe figured prominently with adjustment for IQ. 

CVLT II-- correlations with the body and splenium of the corpus callosum, the parietal and occipital projections of the forceps major bilaterally, the parietal portion of the left superior longitudinal fasciculus, the left inferior longitudinal fasciculus and arcuate fasciculus, the left posterior fornix and cingulum running from the temporal lobe. 

No correlations found for the following tests: JLO, COWAT, DST CS.

Localizaiton of tests within frontal lobes

Stuss DT. Levine B.  Adult clinical neuropsychology: lessons from studies of frontal lobes.  Ann Rev Psychol 2002; 53: 401-433.

Long article, a few (random) points distilled out, heavily tilted towards localization of neuropsych tests within frontal lobes.

Anatomically, the ventral prefrontal cortex is dissociated from the dorsolateral prefrontal cortex (DLPFC).  The former, is associated with emotional regulation, evolutionarily emerged from orbitofrontal and olfactory cortex and limbic nuclei.  It also is important for inhibition, emotion and reward processing.  By contrast, the DLPFC evolutionarily comes from archicortical trend of hippocampus, and is involved in spatial and conceptual processing, including executive functioning.  The frontal poles are more recently evolved and are involved in self awareness, autonoetic consciousness, and humor.

By function:

Frontal lobe language (key reference is Alexander MP et al., 1989 Brain Lang. )  excluding articulation and Broca's aphasia, frontal language function and dysfunction is grouped under activation and formulation (paralinguistics).  Dynamic aphasia, or trouble activating language, occurs after damage to SMA or ACC. TMA, with truncated language, occurs after damage to left DLPFC.  (in other publications, Alexander refers to 'subbcallosal fasciculus').   Usually this is tested using letter fluency.  In Stuss 1998 (JINS) rview of 74 local lesion patients, left DLPFC patients were most impaired, right DLPFC and VPFC patients were not impaired.  However left parietal lesioned patients also were impaired and could not be differentiated from left DLPFC patients.  Superior medial damage on either side (SMA) was associated with poor productions, and posterior superior lateral temporal lesions were implicated .  The latter could be teased out  by switching between letter and semantic fluency tasks.  All above are left sided lesions (except SMA).  Discourse lesions that are left sided include simplification, perseveration and omissions. Right sided lesions may cause amplification of details, wandering from topic, insertion of irrelevancies, and dysprosody, leading to incoherence.

Control of Memory:

Its important to differentiate between basic associative cue-engram processes (medial temporal lobe/hippocampal structures) and strategic processes that may be more top down such as coordination, elaboration and interpretation of these processes.  Wechsler Memory Scale and many others tap both processes but make no effort to dissociate them.  Author cites CVLT as an example of the "Boston approach" that includes efforts to measure serial position learning, semantic organization, interference effects, cued recall, recognition and response bias. Most recent WMS revision has semantically unrelated words, precenting analysis of semantic clustering.  Stuss et al. 1994 Psychology showed right DLPFC lesion patients had more intralist repetitions due to response monitoring defect.  Left frontal caused problems with encoding, retrieval and recognition.  Frontal lobes are important to retrieval involving monitoring, verification, & placement of information especially in spatial and temporal contexts, with lesions causing reduplication, confabulation and retrograde amnesia.  There is a right hemispheric bias in retrieval, but also a DLPFC/VPFC wherein latter is involved in retrieval cue specification and former in higher level postretrieval monitoring (see Fletcher, 1998 Brain, also Petrides). 

Working Memory:
Original idea jacobsen 1936 monkeys with frontal lesions could not make decisions once stimulus was removed from view.  Frontal lobe involvement keeps information online while other areas (slave systems) perform operations.  Frontal involvement increases with interference .  DLPFC monitors and manipulates, whereas VPFC maintains, controls interference and inhibition.  Digit span/spatial span give information about working memory storage capacity but not rehearsal or executive control.  Frontal lesions in one study did not affect digit span.  Reverse digit span measures manipulation of above.  Brown-Peterson technique taps interference.  Supraspan tests measure processing when capacity is exceeded.  Not standard.

Anterior attention processes
Attentional switching:  WCST and TMT, part B.  WCST originally shown by Milner to be response to frontal damage.  New problem solving Dias et al. (J Neurosci 1997).  .  WCST shifts are extradimensional eg. color to form, on basis of feedback, or intradimensional, eg within a color red to blue.  Extradimensional shifts are due to DLPFC in healthy adults.  VPFC damage does not affect extradimensional shifting.  However, VPFC lesions could contribute to the relatively rare error of loss of set due to susceptibility to interference.  DLPFC patients also had loss of set due to loss of sustained attention.Posterior damage also can affect WCST. 

TMT Part B ostensibly uses Part A as an internal control for factors other than switching, but has been criticized as not well matched to Part B in other respects.  Stuss et al. found time correlated with frontal pathology, but effect was eliminated when score was corrected for TMT Part A.  DLPFC patients were distinguished from Part A based on errors but not time.

Selective attention: Stroop test
Stuss found deficit in left sided lesions was due to problems in color naming, not interference.  (Stuss et al., Neuropsychologia 2001).  Patients with superior medial lesions showed errors due to importance of area in maintaining an activated intention.  Inferior medial patients were normal.

Sustained attention:
Continuous performance tests are sensitive to frontal damage especially with increased complexity (eg. respond to "O" after "x".  The Sustained Attention to Response Tast (SART, Robertson 1997 Neuropsychologia) and the Elevator Counting Test (Robertson 1991  the Test of Everyday Attention)

VPFC important in acquiring and reversing stimulus/reward.  The Iowa Gambling Test (Bechara et al.) is based on Somatic Marker Hypothesis, that reasoning is constrained based on previous conditioning, mediated by ventromedial frontal lobes.  VPFC lesions cause "self regulatory disorder" or "SRD."  Another test is the Strategy Application Test, based on the Six Element Test of Shallice and Burgess.  Every patient with focal VPFC damage, especially on right was impaired.  It correlated with outcome questionnaires.

Frontal Pole:  Autobiographical Memory Test.  (Kopelman, 1989J Clin Exper Neuropsychol).  Also, Dysexecutive Questionnaire (Burgess et al, 1996

NPH questionnaires for initial evaluation

from The Neurologist 2010 Wilson et al.

Gait

1. Do you have a problem getting in or out of a seat, walking, or maintaining your balance?
2. How long has it been since you first had this problem?
3. Do you have a problem getting in and out of a car?
4. Do you have a problem starting to walk, as though your feet are stuck to the floor?
5. Do you shuffle or scuff your feet as you walk?
6. Do you have trouble turning?
7. Do you have trouble stepping over a curb or walking on an uneven surface such as grass?
8. Do you touch walls, surfaces or countertops when you walk?
9. In the past month, how often have you fallen?
10. Do you use a cane, walker or wheelchair?

Bladder

1. Do you urinate more frequently than you used to?
2. Do you lose a little urine before reaching the toilet?
3. Do you lose control of your bladder (incontinence)?
4. Do you wear a pad, undergarment or Depends for protection?

Cognition

1. Do you have trouble with your thinking or memory?
2. How long have you had the trouble?
3. Do you have trouble with forgetfulness (repeating questions, difficulty learning, short term memory loss)
4. Do you have trouble with orientation  ( getting lost, disoriented, losing track of time, not recognizing familiar places or persons)
5. Do yo have problems with judgment or solving everyday problems at home such as managing medications, money, cooking, or understanding explanations?
6. Do yo have trouble caring for yourself, for example, bathing, using the toilet,  dressing or eating?
7. Do you have trouble organizing your schedule or routine?