Laura Fratiglioni

Title: Professor

Sector: Medicine

Research group: Debora Rizzuto

Contact

KI Profile page: https://staff.ki.se/people/laura-fratiglioni

Phone: +46 8 524 858 19

Email: laura.fratiglioni@ki.se

Professor Laura Fratiglioni Photo: Maria Yohuang
Professor Laura Fratiglioni Photo: Maria Yohuang

Laura Fratiglioni is a medical doctor from Italy, specialized in both neurology and epidemiology. She moved to Sweden with her family 1996.

Laura is currently employed as a professor at Karolinska Institutet. She was the director of the Aging Research Center (ARC) between 2007 and 2016. In 2010, Laura was granted the Distinguished Professor Award by Karolinska Institutet. She has scientific, clinical, and pedagogical commitments.

Laura’s scientific production has led to 362 articles in peer-reviewed journals, 32 book chapters, and 13 reports. By June 2016 she had 22,800 citations and an h-index of 77 (according to web of science); and 41208 citations and an h-index of 94 (according to google scholar).

Under her supervision, 15 PhD students and 8 postdocs have completed their studies since 1996. She is currently the main supervisor of 2 PhD students, co-supervisor of 6 PhD students, and supervisor of 4 postdocs.

Since 1996, as principal investigator, Laura has regularly received grants from the major research councils in Sweden and from international agencies. Together with a multidisciplinary team of senior researchers, she was awarded a 10-year grant to build ARC by The Swedish Council for Working Life and Social Research (Forte; 11 million Swedish krona per year).

Laura has received several prizes, including the Lifetime Achievement Award from the American Alzheimer’s Association, Sohlberg’s Nordic Prize in Gerontology, and the Karolinska Institutet Folksams prize in epidemiologic research.

Research description

Laura Fratiglioni is the principal investigator of the SNAC-Kungsholmen population study, the scientific coordinator for the Kungsholmen Project on Aging and Dementia, and co-investigator in several Swedish (Swedish Brian Power) and European consortia (NU-AGE, HATICE, ESCAPE; MPI-age). She is the director of The National E-Infrastructure on Aging Research (NEAR). Laura’s research group consists of 18 people, including two lecturers, two assistant professors, six post-docs, seven PhD students, one research assistant, and one research coordinator. We have four major lines of research: 1) Postponing dementia onset: Risk and protective factors for Alzheimer’s disease and other dementias, 2) Understanding the natural history of the dementias, 3) The body-mind connection, and 4) Health status and health trends in older people.

Postponing dementia onset: Risk and protective factors for Alzheimer’s disease and other dementias.

In the last two decades, significant progress has been made regarding the identification of risk and protective factors in dementia. Our group has contributed to the accumulating evidence that lifestyle and cardiovascular risk factors play important roles in the pathogenesis and development of dementia. In addition, we have proposed a life-course model for the development of dementia that is now commonly accepted. This model asserts that a) life-long cumulating lesions (of different kinds) lead to dementia when they no longer can be counteracted by compensatory mechanisms; b) most cases of dementia will occur in late life and most will be of the mixed type (i.e., neurodegenerative and vascular); c) there are specific time windows when some determinants may be active, although not during the whole life period; d) risk and protective factors may interact in both increasing and attenuating their effects on dementia development; e) not all old persons develop dementia, even at advanced ages, and learning from those who “escape” can shed new light on the pathogenesis of dementia; and f) delay of dementia onset seems to be the only realistic endpoint in prevention. Following this model, we are now examining old (vascular and psychosocial factors) and new hypotheses (psychological stress, nutrition, and pollution) with three major goals: a) to identify possible pathways through which protective factors may compensate for previous risk exposures, b) to detect underlying mechanisms, and c) to verify the extent to which established risk and protective factors may anticipate or delay dementia onset.

Understanding the natural history of the dementias from mild cognitive impairment, early detection, and progression to disability, institutionalization, and death.

Cognitive deficits can be observed up to ten years before a dementia diagnosis is made; a sharp decline is more evident in the final three years. Laura and her colleagues have validated the use of such early cognitive deficits as a predictive tool for incipient dementia in the general population, but to date none of the proposed definitions has shown itself to be a sufficiently good predictor at the community level. This is mainly because cognitive impairment is common in the elderly population and has multiple causes. In our ongoing work on this topic, we are examining various individual-difference variables that might modulate both the onset of dementia and the decline once dementia has started. Of special interest here is whether certain favorable conditions (e.g., high educational level, an active lifestyle, advantageous genetic variants) would lead to a later change point and more rapid decline during the final years preceding dementia diagnosis, reflecting greater cognitive reserve. We are also integrating cognitive data with MRI findings to increase the ability to predict dementia onset, whereas social factors are taken into account when studying disability, institutionalization, and death in people affected by dementia.

The body-mind connection

Ongoing demographic changes are expected to lead not only to an increased number of people with chronic diseases, but also to the development of different patterns of diseases, such as multiple health and functional problems, referred to here as chronic multimorbidity (15). Multimorbidity is a very common syndrome in elderly people. It occurs in more than half of the 75+ old population, and the prevalence is higher in very old persons, women, and people from disadvantaged social classes. Almost nothing is known about risk factors for multimorbidity, but the consequences are well established: functional impairment, poor quality of life, and high health-care utilization and costs. We have recently started a new project to study the effect of multimorbidity on cognitive functions. Preliminary data show that multimorbidity affects both the progression from MCI to dementia and the progression of dementia toward functional dependence. Furthermore, specific chronic disorders such as heart failure, atrial fibrillation, and anemia are associated with an increased risk of dementia, which suggests that dementia may also develop in the absence of neurodegeneration. Finally, we have documented a deleterious effect of polypharmacy and of specific chronic disorders (depression, stroke, diabetes) in the development of cognitive impairment. On the basis of these findings, we hypothesize that chronic multimorbidity is a frail state that may anticipate onset of dementia by several years.

Health status and health trends in old ages

Human health is a dynamic and multidimensional status, and this is especially evident in aging, when health changes occur more frequently and at an increased rate. Using data already collected in our cohort studies of middle-aged and elderly people, we are now addressing two research questions: 1) How can we measure the health status of older adults in a more comprehensive way? 2) What are the chains of events that culminate in the development of poor health in elderly people? Specifically, we aim to: 1) integrate multiple health dimensions in a score to better describe health and health trajectories among older adults and to relate health to work capability and societal engagement; 2) quantify the effect of the major social, environmental, psychological, and biological determinants and their life-long interactions on health and survival in older adults; 3) assess geographical variation in mental and physical health and their known determinants in Sweden; and 4) explore time trends in mortality and morbidity among the older population. This research line represents a timely initiative after two decades during which researchers in the aging field (including several from our group) have identified numerous factors that contribute to heath in aging. The challenge is now to understand the interplay among these many factors in a life course perspective, taking into account different components and their impact at the societal level.

Projects (PI)

Education

In 2008 in collaboration with other centers at KI and the universities of Lund and Umeå, Laura started a National Graduate School for Aging Research, which supports an educational program with a biological, psychological, and socio-demographic profile. Preparations for a larger-scale multidisciplinary interaction at the national level are ongoing.

Academic honors, awards and prizes

Prizes

2014 – Italian Society of Gerontology and Geriatics – “Enrico Greppi´s prize”

2013 – Lifetime Achievement Award from the American Alzheimer’s Association

2011 – Wajlit och Eric Forsgrens prize for AD researcher – Umeå University

2010 – The Sohlberg’s Nordic Prize in Gerontology

2010 – Sofiahemmet – Research and Education prize in dementia research

2009 – Karolinska Institutet Folksams prize in epidemiologic research

2008 – The Swedish Society of Medicine – “Inga Sandeborg’s prize”

2001 – Italian Society of Neurology – Award “In memory of Prof L Amaducci”

Awards & Honors

2011 – FAS mid-term evaluation of ARC: “We recommend support at a higher level”

2011 – ERA evaluation (international independent panel): grading “Oustanding”

2010-2015 – The Karolinska  Institutet – Distinguished Professor Award

1996-1999 – Medical Research Council, Sweden – 4-year position as Research Scientist

1990-1993 – Medical Research Council, Sweden – 4-year position as PhD student

Selected publications

Xu WL, Pedersen NL, Keller L, Kalpouzos G, Wang H, Graff C, Winblad B, Bäckman L, Fratiglioni L. HHEX_23 AA genotype exacerbates effect of diabetes on dementia and Alzheimer disease. PLoS Medicine 2015;12:7

Kalpouzos G, Rizzuto D, Keller L, Fastbom J, Santoni G, Angleman S, Graff C, Bäckman L, Fratiglioni L. Telomerase Gene (hTERT) and Survival: Results From Two Swedish Cohorts of Older Adults. J Gerontol A Biol Sci Med Sci 2016;71(2):188-95

Angleman SB, Santoni G, Von Strauss E, Fratiglioni L. Temporal trends of functional dependence and survival among older adults from 1991 to 2010 in Sweden: toward a healthier aging.  J Gerontol A Biol Sci Med Sci 2015 Jun;70(6):746-52

Qiu C, von Strauss E, Bäckman L, Winblad B, Fratiglioni L. Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden. Neurology 2013; 80:20

Ferrari C, Xu W, Wang H, Winblad B, Sorbi S, Qiu C, Fratiglioni L. How can elderly apolipoprotein E epsilon 4 carriers remain free from dementia? Neurobiol Aging 2013; 34:1

Rizzuto D, Orsini N, Qiu C, Wang HX, Fratiglioni L. Lifestyle, social factors, and survival after age 75: population based study. BMJ 2012;345

Wang HX, Wahlberg M, Karp A, Winblad B, Fratiglioni L. Psychosocial stress at work is associated with increased dementia risk in late life. ALZHEIMERS & DEMENTIA 2012;8:2

Wang HX, Gustafson DR, Kivipelto M, Pedersen NL, Skoog I, Winblad B, Fratiglioni L. Education halves the risk of dementia due to apolipoprotein epsilon4 allele: a collaborative study from the Swedish brain power initiative. Neurobiol Aging 2012;33:1007 e1001-1007.

Ferrari C, Xu WL, Wang HX, Winblad B, Fratiglioni L. How can elderly APOE ɛ4 carriers remain free from dementia? Neurobiol Aging 2012 Apr 11. [Epub ahead of print]

Caracciolo B, Bäckman L, Monastero R, Winblad B, Fratiglioni L. The symptom of low mood in the prodromal stage of mild cognitive impairment and dementia: a cohort study of a community dwelling elderly population. J Neurol Neurosurg Psychiatry 2011;82:788-793.

Fratiglioni L, Qiu C. Prevention of cognitive decline in ageing: dementia as the target, delayed onset as the goal. Lancet Neurol. 2011; 10(9): 778-9. (Commentary).

Xu WL, Atti AR, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Midlife overweight and obesity increase late-life dementia risk: a population-based twin study. Neurology 2011;76:1568-15774.

Xu W, Caracciolo B, Wang HX, Winblad B, Bäckman L; Qiu C, Fratiglioni L. Accelerated progression from Mild Cognitive Impairment to dementia in people with diabetes. Diabetes 2010;59:2928-2935.

Marengoni A, Qiu C, Winblad B, Fratiglioni L. Atrial fibrillation, stroke and dementia in the very old: A population-based study. Neurobiol Aging. 2009 Sep 2. [Epub ahead of print].

Wang HX, Karp A, Herlitz A, Crowe M, Kåreholt I, Winblad B, Fratiglioni L. Personality and lifestyle in relation to dementia incidence. Neurology 2009; 72(3): 253-259.

Rosvall L, Rizzuto D, Wang HX, Winblad B, Graff C, Fratiglioni L . APOE related mortality: Effect of dementia, cardiovascular disease and gender. Neurobiol Aging 2009; 30(10):1545-51.

Marengoni A, Winblad B, Fratiglioni L. Response letter to: “Effect of In Utero and Early-Life Conditions on Adult Health and Disease” by Gluckman et al. NEJM 2008; Oct 2;359(14):1523.

Caracciolo B, Palmer K, Monastero R, Bäckman L, Winblad B, Fratiglioni L. Occurrence of cognitive impairment and dementia in the community: a 9-year long prospective study. Neurology 2008; 70(19 Pt 2):1778-85.

Qiu C, Winblad B, Marengoni M, Fastbom J, Fratiglioni L. Heart failure and the risk of Alzheimer’s disease and dementia. Arch Intern Med 2006;166:1003-08.

Atti AR, Palmer K, Volpato S, ZulianiG, Winblad B, Fratiglioni L. Anaemia increases the risk of dementia in cognitively intact elderly. Neurobiol Aging 2006; 27(2): 278-284.

Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 2005; 4: 487-499.

Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112-2117.

Fratiglioni L, Paillard-Borg S, Winblad B. An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol 2004; 3: 343-353.