Andrew D. Blackwell

Characterization of cognitive function with the cantab in individuals with amnestic mild cognitive impairment in relation to hippocampal volume, amyloid, and tau status: Preliminary baseline results from the PharmaCog/european-ADNI study

Braak IV case as compared to a Braak II case. Beside that we also detected an increased presence of ThioflavinS positive NFTs and pThr231 Tau in late stage somata and neurites. In hippocampi however, elevated hyperphosphorylation of pTyr18 and pThr231 Tau occurs already at Braak stages I/II, while NFT formation follows afterwards. Conclusions: Our results suggest especially Tau hyperphosphorylation at residues Tyr18 and Thr231 are early events in hippocampal degeneration and highlight the possible link to early memory loss in AD subjects. Whereas, NFTs, pSer202/Thr205 and pSer262 IR dystrophic neurites present as later stage features. Further studies are warranted to clarify the role of C terminal phosphorylation at Ser396 and Ser422 for the progression of AD.

Mental health versus physical health as determinants of cognition in midlife

Background:We now know that Alzheimer’s pathology develops over many years prior to the emergence of the clinical syndrome. To minimise later risk for dementia, there is increasing emphasis on managing both mental health, including depression, and physical health including cardiovascular and metabolic function, throughout life. The CANTAB paired associates learning (PAL) test is a non-verbal assessment of episodic memory which is, in older adults, highly sensitive to the early signs of Alzheimer’s disease. We investigated the extent to which performance on this test in the general population during middle adulthood is associated with physical and mental health. Methods: At the age of 46 years, 5607 members of the 1966 Northern Finland Birth Cohort completed the CANTAB PAL. This unique longitudinal study has followed from birth 96% of all children born in Northern Finland whose expected day of birth was in the year 1966. Mental health was assessed at ages 31 and 46 using the Hopkins Symptom Check List questionnaire, a 25-item measure including depression and anxiety subscales. Indicators of physical health were reported at age 46 including current smoking status, body mass index, measures of physical activity, and measures of inactivity (time spent sitting). Results: Demographics (sex and education level) together explained 4% of variance in memory scores in midlife. Controlling for these, neither current levels of depression or anxiety, nor depression or anxiety measured 15 years prior were significantly associated with memory performance. Indicators of physical health were significantly associated with memory performance, together explaining a further 3% of variance in cognitive scores. Conclusions: Midlife memory performance is highly influenced by physical health but in this general population birth cohort unaffected by common symptoms of anxiety and depression. This large study provides strong evidence for the importance of lifestyle in determining brain health, even in middle age. Primary and secondary prevention strategies for dementia may need to take into account lifestyle throughout adulthood in determining who is at highest risk and which interventions will be most effective.

Stability of amnestic mild cognitive impairment: Cantab paired associate learning as a predictor of a consistent diagnosis

Background: The initial clinical diagnosis of mild cognitive impairment (MCI) can be unstable, with the degree of cognitive impairment rapidly worsening in some people, and apparently resolving in others. This study used a computerised measure of paired associate learning (Cantab PAL) to predict stable versus transient MCI from baseline cognitive scores. Methods: Participants were recruited from a longitudinal study of neuropsychological function in community-residing adults with suspected MCI. Inclusion criteria were: (i) presence of a subjective cognitive complaints (ii) preserved general cognition; (iii) independent daily functioning. From initial recruitment (n ¼ 286), 200 participants were classified as either amnestic MCI (aMCI: impairments including one or more visual or verbal memory tasks), non-amnestic MCI (na-MCI: impairments in one or more non-memory task) or unimpaired (no cognitive scores <10th percentile relative to normative sample). At 10 month follow-up (n¼122), a number of MCI cases had resolved. The final analysis includes 21 unimpaired controls, 43 with naMCI, 17 with a-MCI, 21 with resolved a-MCI and 43 with resolved na-MCI. Participants underwent Cantab PAL testing as part of their neuropsychological testing at baseline and 10 months. Results: At both baseline and follow-up, PAL performance was significantly worse in a-MCI patients compared to all other groups, which were not significantly different from each other. This included participants initially diagnosed with an initial diagnosis of a-MCI which then resolved. There was a significant interaction between group (a-MCI vs others) and time, indicating that the rate of decline in the a-MCI group was greater than other groups. Logistic regression showed that both PAL impairment at baseline and change in PAL scores predicted a-MCI group membership, even controlling for age, education and gender. Conclusions: The Cantab PAL task is a sensitive and specific indicator of amnestic MCI. Patients who perform badly on this test at baseline are a stable group with a clinically-relevant impairment that worsens steadily over time.

What is a normal change in memory? N=1 classification of clinically relevant cognitive decline

Background: Clinicians often have to decide whether a person’s reported or measured change in cognition reflects normal aging or clinically-relevant cognitive decline. For most cognitive tests, there is no evidence-based guidance for how much change is ‘normal’ over a given timeframe. This study aimed to statistically determine the limits of clinically-significant memory change among healthy older adults and those with mild cognitive impairment (MCI). Methods: Longitudinal cognitive performance was examined in 21 healthy older adults and 81 individuals with clinically-defined MCI. Participants were assessed on Cantab Paired Associate Learning (PAL), a non-verbal episodic memory test, at baseline, 10 months and 20 months as part of a comprehensive neuropsychological assessment. They were classified as amnestic-MCI if there was a deficit (performance <10th percentile relative to norms) in memory tests (with our without impairment in other cognitive tests), and nonamnestic MCI if deficits were limited to non-memory domains. Over the three assessments, MCI was stable, resolved or progressed to dementia. The performance of control participants was used to determine the normal limits for initial and longitudinal change in performance, against which participants with stable or resolved MCI and those who progressed to dementia could be compared on an individual basis. Results: In healthy controls, PAL showed good stability using Bland-Altmann analysis. Na-MCI, and those with resolved MCI performed at a level comparable to healthy controls on each occasion. Patients with stable a-MCI or AD patients were significantly impaired relative to other groups. This persisted even when controlling for age, education, gender and baseline level of performance. Individual estimates of clinically significant impairment and change were able to reliably detect patients who would subsequently develop dementia, or had stable a-MCI. Conclusions: Repeated assessments with the Cantab PAL test are feasible, show good psychometric properties, and can characterise typical and atypical patterns of change in episodic memory. A repeat assessment of memory at <1 year can reliably inform clinical decisions about the presence or absence of pathological cognitive decline.

THE SENSITIVITY AND SPECIFICITY OF COMPUTERISED OR PAPER-AND-PENCIL COGNITIVE ASSESSMENTS USED IN PRIMARY CARE IMPACT THE COST-EFFECTIVENESS OF THE DEMENTIA DIAGNOSTIC PATHWAY

Background: Theory of Mind (ToM) is generally known as an important psychological domain since the eighties, clinical investigations in dementia are scarce. We therefore sought to assess ToM in a large sample of nursing home residents with dementia. We aimed to analyze whether a cognitive impaired person is able to attribute a mental state to oneself and others. We presented firstrespectively second-order-false-belief-tasks. There are only few studies showing the results of such tasks in patients with dementia. Methods:Our hypothesis is a relationship between the degree of severity of the mental deterioration and the corresponding understanding of false beliefs. From a total sample of 397, there were 125 residents of nursing homes who accepted the requirements of our study. A well-established deception task worked out in the research of ToM was modified, the first-respectively second-order-false-belief-tasks were presented to the test persons. Results: A Spearman correlation analysis showed a relationship between the mental deterioration and the lack of recognition of false beliefs in others (r1⁄4 -.396, p< .01).Conclusions:ToM is a necessary life skill for understanding intentions of other persons, which is not least essential in view of the assessment of financial capacity. Regarding limitations of the study, further investigations are required to demonstrate deficits of ToM in nursing home residents.

Early detection of mild cognitive impairment: Would it be cost-effective?

*p<.05, **p<.01 y CDR-Global was not normally distributed and a Spearman’s rho evaluationwas used for correlation analysis between the CDR-Global, CST-Score and CST-time CDR-SOB (Clinical Dementia Rating Scale-Sum of Boxes, ADAS-Cog Total (Alzheimer’s Disease Assessment Scale, Cognitive Subscale Total Score), ADAS-Cog Revised (Alzheimer’s Disease Assessment Scale, Cognitive Subscale Total Score Revised), CDR-Global (Clinical Dementia Rating Scale-Global). Poster Presentations: P3 P638

Verlagswechsel und Reduzierung des Abonnementspreises ab 2004

In der ersten Phase der Therapie ist es geglückt, der Patientin einen Raum zur Verfügung zu stellen, in der gerade in der Distanz der Phantasie eine therapeutische Kommunikation ermöglicht wurde. Diese Phantasie diente dazu, die negative Übertragung der Vater-Figur in der therapeutischen Situation mit mir abzuwehren. Durch die Anteilnahme am «symbolischen Raum» der Patientin wurde eine Annäherung an ihre innere Erlebniswelt möglich. Gleichzeitig konnte ich mir genügend Raum verschaffen – gerade vermittelt über das Verstehen der Figuren als dargestellte Teile ihres Selbst – um ihre Lage benennen und uns dem langsamen Verstehen annähern zu können. Dieser Verstehensprozess ermöglichte das allmähliche «Wissbar-Werden» ihrer inneren Verlassenheitsgefühle, gerade durch die in meiner Gegenübertragung immer wieder deutlich spürbaren und benennbaren Affekte. Diese «haltende Funktion» im Sinne des Containments hat zu einer Transformation emotionaler Inhalte beigetragen, wodurch sich die Patientin in unseren Stunden soweit von ihren frühen negativen Beziehungserfahrungen distanzieren konnte, dass sie mich in einem ersten Versuch als «den hilfreichen Dritten» in der Krisensituation nutzen konnte. Im Verlauf der Stunden und durch die sich abbildenden Prozesse der «Bewusstwerdung» in der Erzählung gelingt es A., die gegensätzlichen Strebungen aus ihrem Unbewussten in eine bewusstseinsnähere Form zu bringen. Ihr Ego-Komplex konnte dadurch an Kraft gewinnen und erlaubte es, sich dem «Undenkbaren» immer weiter anzunähern und schliesslich auszusprechen, wodurch es den Urteilsfunktionen der Patientin verfügbar gemacht werden konnte. Doch noch ist in der Erzählung der Patientin nicht entschieden, ob die Heldin nun von dieser Welt ist oder in das Reich der Götter gehört. Die Wirksamkeit des Unbewussten mit den noch inferioren Urteilsfunktionen wird gerade auf den ersten 62 Seiten, die sie vor der Therapie geschrieben hatte, in erstaunlicher Form sichtbar. Die Heldin muss einen «weiblichen Heldenkampf» um Bewusstheit führen, der im Fortsetzungsteil, der während unserer Therapie entstand, immer sichtbarer wurde. Doch so, wie der Mut der Heldin in der weiteren Entwicklung der Erzählung während unserer Therapiestunden zunimmt, sich ihrer Herkunft zu stellen, beginnt die Patientin auch ihre persönliche Konfliktsituation zu verstehen. Die dabei nun direkter erlebbaren Affekte von Trauer und Wut können nun ähnlich zur Matrix einer «Mutter-Kind-Interaktion» im therapeutischen Raum gehalten werden. Ich meine, dass gerade durch meine Akzeptanz der Abwehrmassnahmen der Patientin, die in dem Angebot der Erzählung verborgen waren, und die Nutzung dieser Erzählung als besondere Form eines Symbolisierungsprozesses, die Möglichkeiten der Patientin gewachsen sind, sich dem Risiko einer vertrauensvollen Beziehung zu stellen, was eben auch eine Modifikation der Komplexe durch neue Beziehungserfahrungen bedeutet. Zum Abschluss meiner Darstellung dieses ersten Therapieschrittes möchte ich noch einmal die junge Heldin der Erzählung (die inzwischen auf 104 Seiten gewachsen ist) zitieren, die folgendes mit ihrer Freundin bespricht und damit die Erweiterung des «Blickwinkels» der Patientin andeutet: «(...) – , wollte ihre Freundin wissen. , bestätigte sie (die Heldin). Plötzlich schaute sie ihre Freundin aufgeregt an. (...)»