also known as white matter hyperintensitie
A clinical trial involving 199 hypertensive older adults (average age 81) found that those who took medicine to keep their 24-hour systolic blood pressure around 130 mm Hg for three years showed 40% less accumulation of white matter lesions compared with those taking medicine to maintain a systolic blood pressure around 145 mm Hg.
60% of the patients maintained their target blood pressure throughout the full three years, and data from these alone showed an even bigger difference in number of brain lesions.
The study used around-the-clock ambulatory blood pressure monitors, which measured participants' blood pressure during all activities of daily living.
Participants had an average systolic blood pressure around 150 mm Hg at the beginning of the trial.
The research was presented at the American College of Cardiology's 68th Annual Scientific Session.
A long-running study tracking 1,288 older adults (65+) until their deaths found that the risk and number of brain lesions increased with higher blood pressure. High blood pressure was also linked to increased risk of protein tangles in the brain.
Two-thirds of the subjects had high blood pressure, while about half had one or more brain infarcts. Those with an upper blood pressure of 147 had a 46% higher chance of having one or more lesions.
Data from 223 participants in the Harvard Aging Brain Study found that both elevated brain amyloid levels and higher vascular risk were associated with more rapid cognitive decline, with the most rapid changes seen in those with both factors. The interaction between the two factors appears to be synergistic rather than simply additive — that is, the interaction between vascular factors and amyloid burden produces more risk than would be predicted from simply adding the two together.
Arvanitakis, Z., Capuano, A. W., Lamar, M., Shah, R. C., Barnes, L. L., Bennett, D. A., & Schneider, J. A. (2018). Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology, 91(6), e517. https://doi.org/10.1212/WNL.0000000000005951
 Rabin, J. S., Schultz A. P., Hedden T., Viswanathan A., Marshall G. A., Kilpatrick E., et al.
(2018). Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study.
JAMA Neurology. 75(9), 1124 - 1131.
A French study involving 6,626 older adults (65+) found that having optimal levels in more measures of cardiovascular health (nonsmoking, weight, diet, physical activity, cholesterol, blood glucose and blood pressure) was associated with lower dementia risk and slower rates of cognitive decline. Dementia risk and rates of cognitive decline lowered with each additional metric at the recommended optimal level.
The measures come from an American Heart Association seven-item checklist aimed at preventing cardiovascular disease.
New findings from the large, long-running Whitehall II study revealed that 50-year-olds who had blood pressure that was higher than normal but still below the usual threshold for treating hypertension, were at increased risk of developing dementia in later life.
This increased risk was seen even when they didn’t have other heart or blood vessel-related problems.
The study involved 8,639 people, of whom 32.5% were women. Participants were aged between 35-55 in 1985, and had their blood pressure measured in 1985, 1991, 1997 and 2003. 385 (4.5%) developed dementia by 2017.
Those who had a systolic blood pressure of 130 mmHg or more at the age of 50 had a 45% greater risk of developing dementia than those with a lower systolic blood pressure at the same age. This association was not seen at the ages of 60 and 70, and diastolic blood pressure was not linked to dementia.
Preliminary results from the Systolic Blood Pressure Intervention Trial (SPRINT) has found that aggressive lowering of systolic blood pressure produced significant reductions in the risk of MCI, and MCI/dementia.
The randomized clinical trial compared an intensive strategy with a systolic blood pressure goal of less than 120 mm Hg and a standard care strategy targeting a systolic blood pressure goal of less than 140 mm Hg. The study involved 9,361 hypertensive older adults (mean age 67.9).
The intensive treatment group had a 19% lower rate of new cases of MCI, and the combined outcome of MCI plus probable all-cause dementia was 15% lower. Serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure occurred more frequently in the intensive-treatment group (4.7% vs 2.5%).
Participants were seen monthly for the first 3 months and every 3 months thereafter. Medications were adjusted on a monthly basis and lifestyle modification was encouraged. 30% of the participants were African American and 10% were Hispanic.
Preliminary results from 673 participants in the trial revealed that total white matter lesion (WML) volume increased in both treatment groups, but the increase was significantly less in the intensive treatment group. There was no significant difference in total brain volume change.
The findings were reported at the Alzheimer's Association International Conference (AAIC) 2018 in Chicago.
A long-running study involving 356 older adults (average age 78) found that those with high levels of arterial stiffness were 60% more likely to develop dementia during the next 15 years compared to those with lower levels.
Arterial stiffness is correlated with subclinical brain disease and cardiovascular risk factors, but adjusting for these factors didn't reduce the association between arterial stiffness and dementia — indicating that arterial stiffness and subclinical brain damage markers are independently related to dementia risk.
Arterial stiffening can be reduced by antihypertensive medication and perhaps also healthy lifestyle changes such as exercise. This study found that exercise at an average age of 73 was associated with lower arterial stiffness five years later.
A rat study found that hypertensive rats exhibited larger ventricles, decreased brain volume, and impaired fluid transport. It’s suggested that hypertension interferes with the clearance of macromolecules from the brain, such as amyloid-beta.
Samieri C, Perier M, Gaye B, et al. Association of Cardiovascular Health Level in Older Age With Cognitive Decline and Incident Dementia. JAMA. 2018;320(7):657–664. doi:10.1001/jama.2018.11499
Abell, J. et al. 2018. Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration and threshold used to define hypertension. European Heart Journal. doi:10.1093/eurheartj/ehy288
 Cui, C., Sekikawa A., Kuller L. H., Lopez O. L., Newman A. B., Kuipers A. L., et al.
(2018). Aortic Stiffness is Associated with Increased Risk of Incident Dementia in Older Adults.
Journal of Alzheimer's Disease. 66(1), 297 - 306.
 Mortensen, K. Nygaard, Sanggaard S., Mestre H., Lee H., Kostrikov S., Xavier A. L. R., et al.
(2019). Impaired Glymphatic Transport in Spontaneously Hypertensive Rats.
Journal of Neuroscience. 39(32), 6365 - 6377.
Perivascular spaces are fluid-filled spaces around the cerebral small vessels, commonly seen on brain scans in older adults. They have been thought to be harmless, but a new study challenges this belief.
The study, which looked at older adults who have not yet developed dementia, showed that different markers of small vessel disease reflect distinct pathways of injury. Well-studied markers of small vessel disease include white matter hyperintensities, infarcts and microbleeds, and the most frequent associations in the study unsurprisingly linked white matter hyperintensities and cognition, including language, information processing speed, executive functioning and visuospatial skills.
Much more surprisingly, though, the next most frequent links were between enlarged perivascular spaces and information processing speed and executive functioning.
 Passiak, B. S., Liu D., Kresge H. A., Cambronero F. E., Pechman K. R., Osborn K. E., et al.
(2019). Perivascular spaces contribute to cognition beyond other small vessel disease markers.
Neurology. 92(12), e1309.
Elevated cholesterol levels have been linked to increased risk of Alzheimer's later in life, and APOE4 is known to raise levels of circulating cholesterol, particularly low-density lipoprotein (LDL) ("bad cholesterol"). A new study has investigated whether LDL is also linked to early-onset Alzheimer's.
The study involved genetically testing 2,125 people, 654 of whom had early-onset Alzheimer's, and testing for cholesterol in a subset of 267 participants. It found that APOE4 explained about 10% of early-onset Alzheimer's, which is similar to estimates in late-onset Alzheimer's disease. About 3% of early-onset Alzheimer's cases had at least one of the known early-onset Alzheimer's risk factors (APP, PSEN1, PSEN2).
Those with elevated LDL levels were more likely to have early-onset Alzheimer's disease, compared with patients with lower cholesterol levels. This was true even after the researchers controlled for APOE genotype.
There was no link between HDL (high-density lipoprotein) cholesterol levels and early-onset Alzheimer's, and only a very slight association between the disease and triglyceride levels.
The researchers also found a new possible genetic risk factor for early-onset Alzheimer's disease. Early-onset Alzheimer's cases were higher in participants with a rare variant of a gene called APOB. This gene encodes a protein that is involved in the metabolism of lipids, or fats, including cholesterol.
A long-running study found that women who had normal levels of the “good” cholesterol, HDL, in 1992 had less white matter damage in their brain two decades later.
The data come from 135 participants in the long-running Women's Healthy Ageing Project. The study found that a higher cardiovascular risk score in midlife was associated with a greater degree of white matter hyperintensity lesions 20 years later, but, intriguingly, that this was predominantly driven by HDL cholesterol level, after controlling for age, education, and APOEe4 status.
 Wingo, T. S., Cutler D. J., Wingo A. P., Le N-A., Rabinovici G. D., Miller B. L., et al.
(2019). Association of Early-Onset Alzheimer Disease With Elevated Low-Density Lipoprotein Cholesterol Levels and Rare Genetic Coding Variants of APOB.
JAMA Neurology. 76(7), 809 - 817.
 Aljondi, R., Szoeke C., Steward C., Gorelik A., & Desmond P.
(2018). The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women.
Brain Imaging and Behavior.
A mouse study has shown that, as cells age, their ability to remove damaged proteins and structures declines.
The process of waste management, called autophagy, involves a component within the cell (an autophagosome) engulfing misfolded proteins or damaged structures (putting them in a garbage bag, essentially). The autophagosome then fuses with a second cellular structure, called a lysosome, that contains the enzymes needed to breakdown the garbage, allowing the components to be recycled and reused.
It’s thought that this decline in autophagy makes neurons more vulnerable to genetic or environmental risks.
The mouse study found that aging brought a significant decrease in the number of autophagosomes produced, along with pronounced defects in their structure.
However, activating the protein WIPI2B restored autophagosome formation.
A cleaning process in brain cells called mitophagy breaks down defective mitochondria and reuses the proteins that they consist of. When the process breaks down, defective mitochondria accumulate in brain cells.
Research has now found that this is markedly present in cells from both humans and animals with Alzheimer's. Moreover, when active substances targeted at the cleaning process were tried in live animals, their Alzheimer's symptoms almost disappeared.
A 2015 study found how toxic tau fibrils spread during the early stages of Alzheimer's disease. Apparently the fibrils (accumulations of tau proteins) can be carried from one neuron to another by microglia.
Microglia act as the brain's immune cells, in which role they identify and clear damage and infection. They clear damage by first engulfing dead cells, debris, inactive synapses or even unhealthy neurons, then releasing nano-scale particles called exosomes, which can be absorbed by other cells.
It used to be thought that exosomes simply help the cell to get rid of waste products. It now appears that cells throughout the body use exosomes to transmit information. This requires them to contain both proteins and genetic material, which other cells can absorb. Hence their ability to spread tau protein, and hence, it now seems, their ability to also transport amyloid-beta.
Amyloid plaques and tau tangles are key biomarkers for Alzheimer’s, but research indicates that it is the tau tangles that are the real problem — the main problem with amyloid plaques is that they lead to tau tangles. A new study indicates how that happens.
A mouse study modified the TREM2 genes, which affect the health of microglia. So some mice carried the common variant of the gene, meaning that their microglia were fully functional, and some carried the risky variant, or no gene at all.
When seeded with tau protein from Alzheimer’s patients, those brains with weakened microglia produced more tau tangle-like structures near the amyloid plaques than in mice with functional microglia.
It was also revealed that microglia normally form a cap over amyloid plaques that limits their toxicity to nearby neurons. When the microglia failed to do that, neurons suffered more damage, creating an environment that fostered the formation of tau tangle-like lesions.
The findings were supported by the finding that humans with TREM2 mutations who died with Alzheimer’s had more tau tangle-like structures near their amyloid plaques than people who died with Alzheimer’s but didn’t have the risky gene.
However, it should be noted that in more advanced stages of Alzheimer’s, mice with the common TREM2 variant showed faster plaque growth. This appears to be linked to the gene inducing microglia to produce ApoE, which enhances aggregate formation.
The finding adds to evidence that Alzheimer's treatment has to take into account the stage at which the disease is at.
Another study that modified the TREM2 gene in mice found that the difference between those with the gene and those without was not in the amount of tau tangles, but rather in the way their immune cells responded to the tau tangles. The microglia in mice with TREM2 were active, releasing compounds that in some circumstances help fight disease, but in this case primarily injured and killed nearby neurons. The microglia in mice without TREM2 were much less active, and their neurons were relatively spared.
A study found that, if the gene for the TDP-43 protein was turned off in microglia, its activity increased, and amyloid-beta was removed very efficiently. However, when TDP-43 was switched off in microglia in mice, it didn’t just get better at removing amyloid-beta, but also led to a significant loss of synapses.
Clearly, dysfunction of microglia is a complicated business, and it’s suggested that such dysfunction may be one reason why many Alzheimer's medications reduce amyloid plaques but fail to improve cognition.
Microglia come in many forms. A survey of brain microglia has classified microglia into at least nine distinct groups, including some types never detected in the past. Some types appeared almost exclusively in the embryonic or newborn stages, others only after injury.
One group tended to cluster near the brain's developing white matter. Another appears to be very inflammatory compared with other microglia, and has been found in people with MS.
Microglia were most diverse early in brain development, in the aged brain and in disease.
 Stavoe, A. K. H., Gopal P. P., Gubas A., Tooze S. A., & Holzbaur E. L. F.
(2019). Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons.
(Dikic, I., Marder E., & Hurley J. H., Ed.).eLife. 8, e44219.
 Fang, E. F., Hou Y., Palikaras K., Adriaanse B. A., Kerr J. S., Yang B., et al.
(2019). Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease.
Nature Neuroscience. 22(3), 401 - 412.
Maitrayee Sardar Sinha, Anna Ansell-Schultz, Livia Civitelli, Camilla Hildesjö, Max Larsson, Lars Lannfelt, Martin Ingelsson and Martin Hallbeck, Alzheimer disease pathology propagation by exosomes containing toxic amyloid-beta oligomers, Acta Neuropathologica, published online 13 June 2018, doi: 10.1007/s00401-018-1868-1 https://link.springer.com/article/10.1007/s00401-018-1868-1
 Leyns, C. E. G., Gratuze M., Narasimhan S., Jain N., Koscal L. J., Jiang H., et al.
(2019). TREM2 function impedes tau seeding in neuritic plaques.
Nature Neuroscience. 22(8), 1217 - 1222.
Parhizkar et al. (2019): "Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE", Nature Neuroscience, DOI: 10.1038/s41593-018-0296-9
Leyns C, Ulrich J, Finn M, Stewart F, Koscal L, Remolina Serrano J, Robinson G, Anderson E, Colonna M, Holtzman DM. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proceedings of the National Academy of Sciences. Week of Oct. 9, 2017.
 Paolicelli, R. C., Jawaid A., Henstridge C. M., Valeri A., Merlini M., Robinson J. L., et al.
(2017). TDP-43 Depletion in Microglia Promotes Amyloid Clearance but Also Induces Synapse Loss.
Neuron. 95(2), 297 - 308.e6.
 Hammond, T. R., Dufort C., Dissing-Olesen L., Giera S., Young A., Wysoker A., et al.
(2019). Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes.
Immunity. 50(1), 253 - 271.e6.
Brain scans of 9,772 people aged 44 to 79, who were enrolled in the UK Biobank study, have revealed that smoking, high blood pressure, high pulse pressure, diabetes, and high BMI — but not high cholesterol — were all linked to greater brain shrinkage, less grey matter and less healthy white matter.
Smoking, high blood pressure, and diabetes were the most important factors, but there was also a compound effect, with the number of vascular risk factors being associated with greater damage to the brain. On average, those with the highest vascular risk had nearly 3% less volume of grey matter, and one-and-a-half times the damage to their white matter, compared to people who had the lowest risk.
The brain regions affected were mainly those involved in ‘higher-order’ thinking, and those known to be affected early in the development of dementia.
The associations were as strong for middle-aged adults as for older ones, suggesting the importance of tackling these factors early.
While the effect size was small, the findings emphasize how vulnerable the brain is to vascular factors even in relatively healthy adults. This also suggests the potential of lifestyle changes for fighting cognitive decline.
Although this study didn't itself examine cognitive performance in its participants, other studies have shown links between cognitive impairment and vascular risk factors, particularly diabetes, obesity, hypertension, and smoking.
While type 2 diabetes has been associated with cognitive problems, the mechanism has been unclear. Now a study involving 93 people with type 2 diabetes has found that greater white matter hyperintensities (indicative of cerebral small vessel disease) were associated with decreased processing speed (but not with memory or executive function).
Cox, Simon R. et al. 2019. Associations between vascular risk factors and brain MRI indices in UK Biobank. European Heart Journal. doi:10.1093/eurheartj/ehz100
 Mankovsky, B., Zherdova N., van den Berg E., Biessels G.-J., & de Bresser J.
(2018). Cognitive functioning and structural brain abnormalities in people with Type 2 diabetes mellitus.
Diabetic Medicine. 35(12), 1663 - 1670.
A review and a large study have recently added to the growing evidence that type 2 diabetes is not only a risk factor for Alzheimer's, but is also linked to poorer cognitive function and faster age-related cognitive decline. The amount of this also seems to be related to glucose control in a dose-dependent manner.
Somewhat surprisingly, there is evidence that the association is not linked to vascular factors, but is in significant part explained by neuron loss. That part is not surprising — brains 'naturally' shrink with age, and growing evidence points to the importance of exercise (which promotes the growth of new neurons) in combating that loss. If diabetics are less likely to exercise (which seems likely, given the strong association with obesity), this may, at least in part, account for the greater brain atrophy.
A meta-analysis of 60 studies involving a total of 9815 people with Type 2 diabetes and 69,254 control individuals, has found a small but reliable association between diabetes and poorer executive function. This was true across all aspects of executive function tested: verbal fluency, mental flexibility, inhibition, working memory, and attention.
Unfortunately, effective diabetes management does depend quite heavily on executive function, making this something of a negative feedback cycle.
A long-running U.S. study involving 13,351 adults, has found that cognitive decline over 19 years was 19% greater among those who had diabetes in midlife. Moreover, cognitive decline increased with higher hemoglobin A1c level and longer duration of diabetes.
At the beginning of the study, participants were aged 48-67 (median: 57), and 13% of participants were diagnosed as diabetic. Cognition was tested using delayed word recall, digit symbol substitution, and word fluency tests.
The findings support the view that glucose control in midlife is important to protect against cognitive decline later in life.
A 2013 study showed that almost half of the cognitive impairment seen among diabetics was explained by their loss of gray matter.
Brain scans and cognitive tests of 350 people with Type 2 diabetes and 363 people without diabetes revealed that those with diabetes had more cerebral infarcts and greater shrinkage in specific regions of the brain. Diabetes was associated with poorer visuospatial memory, planning, visual memory, and processing speed. These associations were independent of vascular risk factors, cerebrovascular lesions, or white matter volume, but almost half of the associations were explained by the shrinkage of gray matter in the hippocampus and across the brain.
Vincent, C. & Hall, P.A. 2015. Executive Function in Adults With Type 2 Diabetes: A Meta-Analytic Review. Psychosomatic Medicine, doi: 10.1097/PSY.0000000000000103
 Rawlings, A. M., A. Sharrett R., Schneider A. L. C., Coresh J., Albert M., Couper D., et al.
(2014). Diabetes in midlife and cognitive change over 20 years: a cohort study.
Annals of Internal Medicine. 161(11), 785 - 793.
 Moran, C., Phan T. G., Chen J., Blizzard L., Beare R., Venn A., et al.
(2013). Brain Atrophy in Type 2 Diabetes Regional distribution and influence on cognition.
Diabetes Care. 36(12), 4036 - 4042.
A study using data from the Lothian Birth Cohort (people born in Scotland in 1936) has analyzed brain scans of 638 participants when they were 73 years old. Comparing this data with participants’ earlier reports of their exercise and leisure activities at age 70, it was found that those who reported higher levels of regular physical activity showed significantly less brain atrophy than those who did minimal exercise. Participation in social and mentally stimulating activities, on the other hand, wasn’t associated with differences in brain atrophy.
Regular physical exercise was also associated with fewer white matter lesions. While leisure activity was also associated with healthier white matter, this was not significant after factors such as age, social class, and health status were taken into account.
Unfortunately, this study is reported in a journal to which I don’t have access. I would love to have more details about the leisure activities data and the brain scans. However, although the failure to find a positive effect of stimulating activities is disappointing, it’s worth noting another recent study, that produced two relevant findings. First, men with high levels of cognitive activity showed a significant reduction in white matter lesions, while women did not. Women with high levels of cognitive activity, on the other hand, showed less overall brain atrophy — but men did not.
Secondly, both genders showed less atrophy in a particular region of the prefrontal cortex, but there was no effect on the hippocampus — the natural place to look for effects (and the region where physical exercise is known to have positive effects).
In other words, the positive effects of cognitive activity on the brain might be quite different from the positive effects of physical exercise.
The findings do, of course, add to the now-compelling evidence for the benefits of regular physical activity in fighting cognitive decline.
It’s good news, then, that a small study has found that even frail seniors can derive significant benefits from exercise.
The study involved 83 older adults (61-89), some of whom were considered frail. Forty-three took part in group exercises (3 times a week for 12 weeks), while 40 were wait-listed controls. Participants were assessed for physical capacity, quality of life and cognitive health a week before the program began, and at the end.
Those who took part in the exercise program significantly improved their physical capacity, cognitive performance, and quality of life. These benefits were equivalent among frail and non-frail participants.
Frailty is associated with a higher risk of falls, hospitalizations, cognitive decline and psychological distress, and, of course, increases with age. In the U.S, it’s estimated that 7% of seniors aged 65 to 74, 18% of those aged 75 to 84, and 37% of seniors over the age of 85 are frail.
 Gow, A. J., Bastin M. E., Maniega S M., Hernández M V. C., Morris Z., Murray C., et al.
(2012). Neuroprotective lifestyles and the aging brain Activity, atrophy, and white matter integrity.
Neurology. 79(17), 1802 - 1808.
 Langlois, F., Vu T T M., Chassé K., Dupuis G., Kergoat M-J., & Bherer L.
(2012). Benefits of Physical Exercise Training on Cognition and Quality of Life in Frail Older Adults.
The Journals of Gerontology Series B: Psychological Sciences and Social Sciences.
First study: http://www.eurekalert.org/pub_releases/2012-10/aaon-emt101712.php
Second study: http://www.eurekalert.org/pub_releases/2012-09/uom-etv090612.php
Damage to the retina (retinopathy) doesn’t produce noticeable symptoms in the early stages, but a new study indicates it may be a symptom of more widespread damage. In the ten-year study, involving 511 older women (average age 69), 7.6% (39) were found to have retinopathy. These women tended to have lower cognitive performance, and brain scans revealed that they had more areas of small vascular damage within the brain — 47% more overall, and 68% more in the parietal lobe specifically. They also had more white matter damage. They did not have any more brain atrophy.
These correlations remained after high blood pressure and diabetes (the two major risk factors for retinopathy) were taken into account. It’s estimated that 40-45% of those with diabetes have retinopathy.
Those with retinopathy performed similarly to those without on a visual acuity test. However, testing for retinopathy is a simple test that should routinely be carried out by an optometrist in older adults, or those with diabetes or hypertension.
The findings suggest that eye screening could identify developing vascular damage in the brain, enabling lifestyle or drug interventions to begin earlier, when they could do most good. The findings also add to the reasons why you shouldn’t ignore pre-hypertensive and pre-diabetic conditions.
 Haan, M., Espeland M. A., Klein B. E., Casanova R., Gaussoin S. A., Jackson R. D., et al.
(2012). Cognitive Function and Retinal and Ischemic Brain Changes The Women's Health Initiative.
Neurology. 78(13), 942 - 949.
Data from the very large and long-running Cognitive Function and Ageing Study, a U.K. study involving 13,004 older adults (65+), from which 329 brains are now available for analysis, has found that cognitive lifestyle score (CLS) had no effect on Alzheimer’s pathology. Characteristics typical of Alzheimer’s, such as plaques, neurofibrillary tangles, and hippocampal atrophy, were similar in all CLS groups.
However, while cognitive lifestyle may have no effect on the development of Alzheimer's pathology, that is not to say it has no effect on the brain. In men, an active cognitive lifestyle was associated with less microvascular disease. In particular, the high CLS group showed an 80% relative reduction in deep white matter lesions. These associations remained after taking into account cardiovascular risk factors and APOE status.
This association was not found in women. However, women in the high CLS group tended to have greater brain weight.
In both genders, high CLS was associated with greater neuronal density and cortical thickness in Brodmann area 9 in the prefrontal lobe (but not, interestingly, in the hippocampus).
Cognitive lifestyle score is produced from years of education, occupational complexity coded according to social class and socioeconomic grouping, and social engagement based on frequency of contact with relatives, neighbors, and social events.
The findings provide more support for the ‘cognitive reserve’ theory, and shed some light on the mechanism, which appears to be rather different than we imagined. It may be that the changes in the prefrontal lobe (that we expected to see in the hippocampus) are a sign that greater cognitive activity helps you develop compensatory networks, rather than building up established ones. This would be consistent with research suggesting that older adults who maintain their cognitive fitness do so by developing new strategies that involve different regions, compensating for failing regions.
 Valenzuela, M. J., Matthews F. E., Brayne C., Ince P., Halliday G., Kril J. J., et al.
(2012). Multiple Biological Pathways Link Cognitive Lifestyle to Protection from Dementia.
Biological Psychiatry. 71(9), 783 - 791.
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