Effects of a 6-month cognitive intervention program on brain metabolism in amnestic mild cognitive impairment and mild Alzheimer's disease.

The effect of cognitive intervention on brain metabolism in Alzheimer's disease (AD) is largely unexplored. Therefore, we aimed to investigate clinical cognitive parameters and 18FDG PET to test for effects of a cognitive intervention in patients with amnestic mild cognitive impairment (aMCI) or mild AD. Patients with aMCI (n = 24) or mild AD (n = 15) were randomly assigned either to cognitive intervention groups (IGs), receiving weekly sessions of group-based multicomponent cognitive intervention, or active control groups (CGs), receiving pencil-paper exercises for self-study. We obtained resting-state FDG-PET scans and neuropsychological testing at baseline and after six-months. Normalized FDG-PET images were analyzed using voxel-based SPM5 approaches to determine longitudinal changes, group-by-time interactions, and correlations with neuropsychological outcome parameters. Primary global cognitive outcome was determined by analyses of covariance with MMSE and ADAS-cog scores as dependent measures. Both, aMCI and AD subgroups of CGs showed widespread bilateral cortical declines in FDG uptake, while the AD subgroup of IGs showed discrete decline or rather no decline in case of the aMCI subgroup. Group by time analyses revealed strongest attenuation of metabolic decline in the aMCI subgroup of the IGs, involving left superior temporal- and anterior cingulate gyrus. However, correlation analyses revealed only weak non-significant associations between increased FDG uptake and improvement in primary or secondary outcome parameters. Concurrently, there was significant improvement in global cognitive status in the aMCI subgroup of the IGs. A six-month cognitive intervention imparted cognitive benefits in patients with aMCI, which were concurrent with an attenuated decline of glucose metabolism in cortical regions affected by neurodegenerative AD.

[1]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[2]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[3]  K. Davis,et al.  A new rating scale for Alzheimer's disease. , 1984, The American journal of psychiatry.

[4]  J. Morris,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer's disease , 1989, Neurology.

[5]  Karl J. Friston,et al.  Comparing Functional (PET) Images: The Assessment of Significant Change , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  M. Lachman,et al.  Improving memory and control beliefs through cognitive restructuring and self-generated strategies. , 1992, Journal of gerontology.

[7]  K. Herholz,et al.  Activation PET as an Instrument to Determine Therapeutic Efficacy in Alzheimer's Disease a , 1993, Annals of the New York Academy of Sciences.

[8]  P. Scheltens,et al.  A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging , 1993, Journal of the Neurological Sciences.

[9]  R. Koeppe,et al.  A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  S. Thibodeau,et al.  Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. , 1996, The New England journal of medicine.

[11]  N. Foster,et al.  Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease , 1997, Annals of neurology.

[12]  B. Reisberg,et al.  Retrogenesis: clinical, physiologic, and pathologic mechanisms in brain aging, Alzheimer’s and other dementing processes , 1999, European Archives of Psychiatry and Clinical Neuroscience.

[13]  J. Hodges,et al.  Attention and executive deficits in Alzheimer's disease. A critical review. , 1999, Brain : a journal of neurology.

[14]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[15]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[16]  K. Ishii,et al.  Statistical brain mapping of 18F-FDG PET in Alzheimer's disease: validation of anatomic standardization for atrophied brains. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  G. Alexander,et al.  Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer's Disease Treatment Studies. , 2002, The American journal of psychiatry.

[18]  Karl Herholz,et al.  PET studies in dementia , 2003, Annals of nuclear medicine.

[19]  A. Drzezga,et al.  Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[20]  S Minoshima,et al.  Cerebral glucose metabolism in patients with AD and different APOE genotypes , 2005, Neurology.

[21]  P. Sachdev,et al.  Brain reserve and dementia: a systematic review , 2005, Psychological Medicine.

[22]  Yaakov Stern,et al.  Cognitive reserve and Alzheimer disease. , 2006, Alzheimer disease and associated disorders.

[23]  G. Small,et al.  Effects of a 14-day healthy longevity lifestyle program on cognition and brain function. , 2006, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[24]  Vinod Menon,et al.  Where and When the Anterior Cingulate Cortex Modulates Attentional Response: Combined fMRI and ERP Evidence , 2006, Journal of Cognitive Neuroscience.

[25]  D. Jeste,et al.  Cognitive training in Alzheimer's disease: a meta‐analysis of the literature , 2006, Acta psychiatrica Scandinavica.

[26]  Daniel S. Margulies,et al.  Mapping the functional connectivity of anterior cingulate cortex , 2007, NeuroImage.

[27]  Alexander Hammers,et al.  Choice of reference area in studies of Alzheimer's disease using positron emission tomography with fluorodeoxyglucose-F18 , 2008, Psychiatry Research: Neuroimaging.

[28]  Albert Gjedde,et al.  Normalization in PET group comparison studies—The importance of a valid reference region , 2008, NeuroImage.

[29]  Sylvie Belleville,et al.  Cognitive training for persons with mild cognitive impairment , 2008, International Psychogeriatrics.

[30]  Albert Gjedde,et al.  Subcortical elevation of metabolism in Parkinson's disease — A critical reappraisal in the context of global mean normalization , 2009, NeuroImage.

[31]  Perminder Sachdev,et al.  Can cognitive exercise prevent the onset of dementia? Systematic review of randomized clinical trials with longitudinal follow-up. , 2009, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[32]  Nikolai Axmacher,et al.  Activation of the caudal anterior cingulate cortex due to task‐related interference in an auditory Stroop paradigm , 2009, Human brain mapping.

[33]  Alexander Hammers,et al.  SPM-based count normalization provides excellent discrimination of mild Alzheimer's disease and amnestic mild cognitive impairment from healthy aging , 2009, NeuroImage.

[34]  Albert Gjedde,et al.  Data-driven intensity normalization of PET group comparison studies is superior to global mean normalization , 2009, NeuroImage.

[35]  Harald Hampel,et al.  Cognitive intervention in Alzheimer disease , 2010, Nature Reviews Neurology.

[36]  Paul Cumming,et al.  FDG-PET mapping the brain substrates of visuo-constructive processing in Alzheimer's disease. , 2010, Journal of psychiatric research.

[37]  Bob Woods,et al.  Nonpharmacological Therapies in Alzheimer’s Disease: A Systematic Review of Efficacy , 2010, Dementia and Geriatric Cognitive Disorders.

[38]  D. Rujescu,et al.  Effects of a newly developed cognitive intervention in amnestic mild cognitive impairment and mild Alzheimer's disease: a pilot study. , 2011, Journal of Alzheimer's disease : JAD.

[39]  Gerd Wagner,et al.  Structural brain alterations in patients with major depressive disorder and high risk for suicide: Evidence for a distinct neurobiological entity? , 2011, NeuroImage.