DNA Bank for Cognitive Genetic Studies

Taken at 5 yearly intervals in two test batteries (TB1, TB2) each requiring 90 minutes

General-Fluid Intelligence

• Heim (part 1 AH1 and part 2 AH2; 65 questions each, TB1)

The AH1 tests include number series, verbal comparisons, logical problems and arithmetical problems. The AH2 test consists of non-verbal problems that involved the mental rotation of shapes and addition or subtraction of patterns.
Heim AW. AH4 Group Test of General Intelligence. NFER-Nelson: Windsor UK, 1970

Cattell Culture Fair (TB2)

Four parts of the Culture Fair test are used. Each part consists of non-verbal questions. All 4 scores are totalled to give a final score.
Catell RB and Cattell AKS. 1960. The individual or group Culture Fair intelligence test. I.P.A.T. Champaign, Illinois.

Vocabulary

• Mill Hill vocabulary (part A and B; crystal intelligence-verbal; TB1)

The MHA comprises of 33 words and the volunteer must select the correct synonym from a choice of six. MHB requires the exact meaning of 33 words.
Raven JC. The Mill Hill Vocabulary Scale. HK Lewis; London, 1965

• WAIS vocabulary test (Define 35 words; TB2)

Consists of 40 words with the first 3 given as examples. Volunteers are asked to give definitions for 37 words. Definitions are scored 0, 1, or 2.
Weshler D. 1986. The Wechsler Adult Intelligence Test-Revised. The Psychological Corporation, New York.

Processing Speed

• Alphabet Coding Task (TB2)

The Savage ACT task requires volunteers to encode 15 different letter sequences using a substitution code as quickly as possible. The test consists of examples and a practice followed by 4 consecutive trials of 2 minutes duration each. The maximum score for each trial is 200. Total score is the number of correct letters encoded in all 4 trials.
Savage RD. 1984. Alphabet Coding Task-15. Published by Murdock University, Perth, W.Australia.

• Random Letters (TB2)

The RL test allows participants 8 minutes to detect all O and I letters on 4 pages of random letters administered as 4 separate tests of two minutes each. Scores are based on the number of letters spotted and the number omitted. Maximum score possible is 316. This test is a measure of speed and of accuracy.

Free recall 30 test (verbal immediate recall; TB2)

30 six-letter nouns that are flashed one at a time on a screen at 2 second intervals. Volunteers are then asked to write down as many as they remember in any order.

Free recall 10 test (verbal immediate and delayed recall; TB2)

Identical to the FR30 test with the exception that only 10 nouns are used. Volunteers are given a surprise delayed recall test 20 minutes after the session when they are asked to remember as many of the 10 words as they can.

Cumulative recall (verbal recall and learning; TB1)

15 six-letter nouns that are presented in the same way as the FR30 test. The volunteers must write down as many words as they can remember in any order. This is repeated 4 consecutive times using the same words in the same order.

Memory recognition (delayed non-verbal recognition; TB1)

40 uncoloured Schultz “Snoopy” cartoon slides that are shown at a rate of 1 every 2 seconds.  After seeing the original 40 slides there is an immediate recall. The volunteers are shown 10 of the original slides along with 10 slides that are not part of the original 40. Scores are given for the number of targets correctly identified as being either part of the original 40 or a distracter.

Semantic memory (verbal semantic cued recall; TB2)

15 slides containing 5 pieces of information: a forename, city of residence, hair colour and occupation of five imaginary individuals were shown to volunteers for 3 seconds each. Scores are assigned for correct information given to correct person (PTC) and misplaced memory (PMM) (correct information but assigned to wrong person). Total score for this test is 15.

Baddeley semantic reasoning test (processing speed and semantic memory; TB2)

One-hundred and fifty sentences half correct and half incorrect identified true or false in 2 minutes; scores total correctly identified true or false.

Memory circle (immediate verbal recall and spatial; TB2)

Circle divided into 12 quadrants with a line drawing in each of easily nameable object: Immediately after asked to recall the names of the objects and enter them into 12 sectors of a blank circle: scored number objects correctly named, number of sectors filled and number sectors filled correctly.

Memory for shapes and location (non-verbal immediate recall and spatial; TB2) 

Shapes of geometric figures in sixteen separate 4x4 matrices: shown as subsets of four matrices containing 1,2,3, or 4 shapes: Matrices containing 1,2,3,or 4 shapes shown. Recorded number of shapes correctly recalled and number of grid cells correctly identified as occupied and the numbers of shapes correctly assigned to the grid cells in which they had appeared.

• Age, gender, education, income, social activity, cause of parental mortality
• Socio-economic status based on six categories (C): C1 professional,C2 Intermediate, C3(N) non-manual skilled, C3(M) manual skilled, C4 partly skilled, C5 unskilled
• Cornell Medical Index: 220 health related questions
• Eysenck Personality Questionnaire (EPQ-R 90 questions)
• Beck / Yesavage depression scales and life events scores
• Depression scores collected at 6 time points

Michelle Luciano, et al. Genome-wide association uncovers shared genetic effects among personality traits and mood states. Am J Med Genet B Neuropsychiatr Genet. 2012 159B(6):684-95.

• Balance, mobility, grip strength
• Dysphasia
• Pain
• Sleep
• BMI (540 volunteers)
• Waist/Hip Ratio (540 volunteers)

Normalized volumes of the left and right hippocampus, temporal lobe, and hemisphere were estimated in 135 elderly subjects using a stereological procedure. For all these subjects, a T1-weighted image pulse sequence with TR of 24 ms, TE of 11 ms and flip angle of 30 was acquired on a 1.5 Tesla Philips N.T. whole body MRI system. The acquisition provided 160 images comprising contiguous 1.77mm thick slices through the brain with a field of view of 23 cm, and an acquisition matrix of 256 readings of 128 phase encodings.

The images were realigned using the NRIA2 software (Brain Behaviour Laboratory, University of Pennsylvania) and linearly interpolated to 296 slices, comprising cubic voxels of side 0.898 mm. The volumes of the left and right hippocampus, temporal lobes and hemispheres were measured using image sections that were oriented perpendicularly to the long axis of the hippocampus. A point counting procedure was used with structural boundary markers as previously described (for example, see Mackay et al., 1998). These volume estimates were normalized by dividing each subject’s structural volumes by a measure of his or her total cranial volume in order to control for variations in peak brain size in youth.

Further details on the cohort can be obtained from:
Rabbitt P, Diggle P, Horan M, Pendleton N, Bent N, Abson V et al. The University of Manchester Longitudinal Study of normal healthy old age 1983 through 2003. Aging Neuropsychology and Cognition 2004; 11: 245-279.

Approximately 3-400 volunteers from the Dyne Steel cohort have agreed to donate their brains after death. Approximately 50 brains have been collected so far and it is estimated that 200-250 volunteers will complete the agreement.

QC’d GWAS data exists for 1850 volunteers. Genotyping was performed using the Illumina 610 quad array and has been imputed to 2 million SNPs. The GWAS study was a collaborative study with the University of Edinburgh who used the Lothian Birth Cohorts 1921 and 1936 (See following references for details and results of this work)

Gail Davies, Sarah Harris, Chandra Reynolds, Antony Payton et al. A Genome-Wide Association Study implicates the APOE locus in non-pathological cognitive ageing. Molecular Psychiatry 2012. In press.

Gail Davies, Albert Tenesa, Antony Payton, et al. Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Mol Psychiatry. 2011: 16(10):996-1005.

All participating volunteers are screened approximately annually by telephone to seek evidence of dementia. Screening is performed using both TICSm and GDS with scores of below 22 or above 5, respectively, resulting in the offer of a home assessment. A common cause of failure is hearing impairment which is assessed using the hearing handicap inventory. Tests include CLOX, ACE-R (MMSE embedded), HADS, qMCI, verbal fluency (F, A, S, P and animals), IQCODE (informant questionnaire) and the Dementia Severity Rating Scale (informant questionnaire). The following may also be performed: TICSm, severe MMSE, AMTS and Frontal Assessment Battery.

A proportion of volunteers (North West England) are offered assessment at the Cerebral Function Unit if MMSE is 23 or less and the GDS is less than 5.

Other sample types are available from this cohort such as plasma, lymphocytes, urine (available on approximately 400 volunteers).

The programme has 2 cohorts of volunteers from the North East (Newcastle) and the North West (Manchester) of the UK. The original cohort was on 3 occasions added to with refreshment samples. These are shown below:

Batch 1, 2, 3

Started 1985 Manchester and Newcastle B1,2,3 and DMS 1982/1983

Year	Number complete Manchester	Number complete Newcastle	Electronic or paper
1982/1983	-	N=1839	Electronic
1985/88	N=1872	N=1563	Electronic
1990/1992	N=1039	N=959	Electronic
1995/1996	N=821	N=650	Electronic
1999/2000	N=571	N=350	Electronic
2001/2002	N=401	-	-
2002/2003	N=378	-	-
2004/2005	N=395	N=158	Electronic
2007/2008	N=332	N=141	Electronic
2008/2010	N=280	N=120	Electronic

Batch 4

1989/1990 Manchester and Newcastle 1988

Year	Number complete Manchester	Number complete Newcastle	Electronic or paper
1989/90	N=336	N=579	Electronic
1991	-	N=415	Electronic
1995/1996	N=218	N=314	Electronic
1999	N=175	N=10	Electronic
2001/2002	N=128	-	-
2003	N=126	-	Electronic
2004/2005	N=114	N=66	Electronic
2004/2005	N=395	N=158	Electronic
2007/2008	N=103	N=68	Electronic
2008/2010	N=95	N=62	Electronic

Batch 5

Manchester 1991

Year	Number complete Manchester	Number complete Newcastle	Electronic or paper
1989/90/1991	N=83	-	Electronic
1995/1996	N=55	-	Electronic
1999	N=47	-	Electronic
2001/2002	N=39	-	-
2003	N=39	-	Electronic
2004/2005	N=31	-	Electronic
2007/2008	N=27	-	Electronic
2008/2010	N=24	-	Electronic

Newcastle Batch 5 and 6

1989/90 & Batch 7 Newcastle 1992

Year	Number complete Manchester	Number complete Newcastle	Electronic or paper
1989/90 or1992	-	N=601	Electronic
1995/1996	-	N=416	Electronic
2000	-	N=16	Electronic
2004/2005	-	N=106	Electronic
2007/2008	-	N=88	Electronic
2008/2010	-	N=75	Electronic

Summary of data available cognitive data

	Manchester	Newcastle	Total
Test Battery 1 x one test	2645	3250	5895
Test Battery 1 x two tests	1419	2337	3756
Test Battery 1 x three tests	869	1247	2116
Test Battery 1 x four tests	436	549	985
Test Battery 2 x one test	1948	2285	4233
Test Battery 2 x two tests	1066	1352	2418
Test Battery 2 x three tests	792	399	1191
Test Battery 2 x four tests	511	0	511
TICS/GDS x one test	525*	338*	863*
TICS/GDS x two tests	462*	304*	766*
TICS/GDS x three tests	399*	283*	662*

Summary of Mood data available

Year	Manchester	Newcastle	Total
1982/1983	-	Beck	1893
1985/1988	Beck	Beck	3435
1990/1992	Yesavage 30	Yesavage 30	3597
1995/1996	Yesavage 30	Yesavage 30	2474
1999/2000	Yesavage 30	Yesavage 30	1169
2001/2002	Beck	-	568
2002/2003	Yesavage 30	-	543
2004/2005	Yesavage 15*	Yesavage 15*	863*
2007/2008	Yesavage 15*	Yesavage 15*	766*
2008/2010	Yesavage 15*	Yesavage 15*	662*

* indicates telephone assessment

Further Publications Involving the Dyne Steel Cohort are available upon request.