The diagnosis of Alzheimer’s disease is making amazing progress. But not only high-tech PET and biomarkers indicate the onset of dementia; gait irregularities can also provide clues to a disease at a very early stage. At the very well attended second Basel Dementia Forum, a series of lectures, workshops and remarkable theatrical performances provided a deep insight into the topic.
A new diagnostic method, positron emission tomography (PET), can visualize deposits typical of Alzheimer’s disease, such as β-amyloid plaques. For the examination, the patient is administered radionuclides, which then bind to the diseased structures in the brain. If the PET is negative, that is a very good indication that the patient really does not have Alzheimer’s disease. However, when PET is positive, false positives occur in 10-30% of affected individuals. “Therefore, PET will not be the universal solution,” explained Prof. René Müri, MD, of Inselspital Bern, Switzerland, at the second Basel Dementia Forum.
Into the future with biomarkers
Different biomarkers can also now be used to detect early brain changes. If the clinical delineation of the disease is uncertain, it is recommended by neurological-psychiatric societies to use biomarkers. For example, the concentration of tau protein in CSF is significantly altered several years before the clinical onset of disease. The most common biomarkers within AD diagnostics are considered to be decreased β-amyloid 42 peptide (Ab42), decreased Ab1-42/Ab1-40 ratio, increased total tau protein (T-tau), and increased phospho-tau. Although recent studies confirm the high value of such biomarkers, their informative value decreases with increasing patient age due to high variability [1]. In addition, according to a recent Swedish paper, other neurologic diseases, such as herpes simplex-1 encephalitis, can confound the diagnostic picture and should therefore be taken into account when evaluating results, said the Bern neurologist [2].
In a recent paper, a Swiss expert group summarized a consensus on the diagnosis and treatment of dementia patients [3]. At the moment, great efforts are being made to obtain biomarkers not only from cerebrospinal fluid, but also – much more simply – from blood. For example, a recent study identified a whole series of potentially interesting proteins that differ between Alzheimer’s and non-Alzheimer’s patients. “This is certainly not yet conclusive, and follow-up studies are needed, but this could be a simple way to get additional information for diagnostics,” Prof. Müri said. In other studies, the aim is also to enable healthy relatives – and especially the children of those affected – to be diagnosed with biomarkers at an early stage. “Of course, this also has ethical consequences,” Prof. Müri continues, “because what good does it do me if I know that I will develop Alzheimer’s in ten years’ time? Nothing now, probably.”
Interesting case presentations
With two detailed case presentations, Dr. med. Hans Pihan from the Memory Clinic at the Spitalzentrum Biel was able to captivate the audience. Among them is the case of a 59-year-old man who was admitted to his workplace due to concentration and increasing memory disorders, as well as serious failures. Thus, agreements and appointments were forgotten, but also objects were not found again, or wrongly classified. Several behavioral neurological tests, including the clock test, which involves recording a time, or the “Boston Naming Test,” which examines the recognition and naming of objects, were mastered only very incorrectly. In contrast, short sentences could be read and written and spontaneous speech utterances could be reproduced completely correctly in terms of content and grammar. Apart from markedly elevated tau levels, the CSF showed otherwise quite unremarkable biomarker levels. The man was diagnosed with “posterior cortical atrophy” (PCA). This probable special form of Alzheimer’s disease is characterized by the fact that the relatively young sufferers (about 60 years) primarily suffer from disorders of visual spatial perception. Typical early symptoms are “unclear visual disturbances” with impairments in drawing, writing, arithmetic, reading clocks, or clearing in and out (e.g., when setting a table). “What is impressive about this clinical picture, however, and what deceives many, is that they have good communication skills and good disorder awareness,” Dr. Pihan noted.
Dementia recognizable from the gait
Can you tell if someone has dementia, or at least is on their way there, by their gait? For several years, the teams led by Prof. Reto W. Kressig, MD, and Prof. Andreas Monsch, MD, of the Basel Mobility Center and the Memory Clinic of the Acute Geriatrics Department of the University Hospital Basel have been studying the relationship between brain performance and gait disorders. “Even the smallest change is associated with an increased risk of falls,” Prof. Kressig said. For example, a step change of just 1.7 centimeters doubles the risk of falls in seniors living at home. The more dementia progresses, the more pronounced the gait irregularities. In the New York “Einstein Aging Study”, older healthy people were regularly subjected to various gait tests [4]. About a decade later, analysis of these data pointed to interesting correlations. Thus, those who later developed dementia showed increased gait variability five years earlier. Therefore, it is suspected that subtle gait irregularities occur even before symptoms of reduced brain performance are detected.
“Walk and Talk” as a challenge
However, step changes of just under two centimeters are hardly visible to the eye. In the Basel Mobility Center of the Acute Geriatrics Department of the University Hospital Basel, there is therefore a long carpet in which 30,000 sensors are installed. Step length, step duration, step width, gait speed and other gait parameters can be calculated from the gait analyses. If a step variability of more than 4% is now measured, gait insecurity must be assumed, according to the Basel expert. This makes use of a remarkable characteristic of the human gait: although walking speed and step length decrease with age, the step cadence, i.e. the number of steps per minute, and the regularity of the gait remain the same even in seniors – provided they are healthy. A simple “walk and talk” test also demonstrated a correlation between brain conduction and motor function [5]. For this purpose, elderly subjects were asked, for example, for the name of their eldest grandchild while walking [6]. More than three-quarters of the participants who had to stand still to give their answer fell at least once over the next six months, in contrast to those who were able to give their answer from walking. Counting backwards while walking also poses major problems for patients with early dementia and causes gait disturbances that do not occur in healthy individuals of the same age [7]. Such measurements could be a tool for both detecting an increased tendency to fall (and thus initiating appropriate fall prevention measures), but also for diagnosing incipient dementia at an early stage, according to Prof. Kressig.
Fewer falls due to rhythm and music
Is it now possible to counteract incipient gait irregularities by therapeutic measures? Certain repetitive physical activities such as dance, rhythm, or others seem to promote steady walking. In Basel, studies wanted to know more precisely whether special exercises can improve executive function. In fact, a special tai chi program decreased both gait width and gait cycle variability in the elderly, improving walking. “Gait becomes more secure again if you are cognitively and motorically active at the same time,” the geriatrician tips. Another option is to include music. A prime example is the Jaques-Dalcroze rhythm, which has also been used with seniors for several years. In a fall prevention study of 134 healthy seniors in Geneva, attending a rhythm class just once a week led to significantly safer walking among seniors and a reduction in fall events by half [8].
Check fitness to drive
Finally, Prof. Monsch presented the important new consensus recommendations on fitness to drive in cognitive impairment [9]. An algorithm is used to determine exactly in which situation a recommendation to refrain from driving should be made, or when a report to the road traffic authorities should be considered. A control drive can also provide more clarity, as Andrea Rothenberger from the Road Traffic Office of the Canton of Graubünden in Basel explained.
The successful and exceptionally well-attended event was rounded off by sensitive and very entertaining contributions from the “Hirntheater” under the direction of Franziska Maria von Arb from Liestal.
Dr. Klaus Duffner
Source: 2nd Basel Dementia Forum, November 22, 2012
Literature:
- Mattson N, et al: Age and diagnostic performance of Alzheimer disease CSF biomarkers. Neurology 2012; 78: 468-478.
- Krut JJ, et al: Cerebrospinal fluid Alzheimer’s biomarker profiles in CNS infections. J Neurol. 2012; http://dx.doi.org/10.1007/s00415-012-6688-y
- Monsch AU, et al: Consensus 2012 on diagnosis and therapy of dementia patients in Switzerland. Praxis 2012; 101(19): 1239-1249.
- Verghese J, et al: Quantitative gait dysfunction and risk of cognitive decline and dementia. J Neurol Nerosurg Psychiatry 2007; 78: 929-935.
- Kressig R: The role of clinical gait analysis. Health and Science. Novartis Pharma Switzerland 2011.
- Lundin-Olsson L , Nyberg L, Gustafson Y: “Stops walking when talking” as a predictor of falls in elderly people. Lancet 1997; 349: 617.
- Bridenbaugh SA, Monsch AU, Kressig RW: How does gait change as cognitive decline progresses in the elderly? AAIC Vancouver 2012; Poster P1-073.
- Trombetti et al: Effect of Music-Based Multitask Training on Gait, Balance, and Fall Risk in Elderly People. A Randomized Controlled Trial. Arch Intern Med 2011; 171(6): 525-533.
- Mosimann UP: Consensus recommendations for assessing minimum medical requirements for fitness to drive in cognitive impairment. Praxis 2012; 101 (7): 451-464.
